Podcasts about rp1

Kemendagri berencana menaikkan dana bantuan parpol pemilik kursi di DPR menjadi Rp3 ribu per suara. Usulan itu muncul dalam rapat Anggaran Pendapatan dan Belanja Negara (RAPBN) di Komisi II DPR, Selasa (8/7).Dana bantuan saat ini sebesar Rp1 ribu per suara, sudah naik dari sebelumnya Rp108 per suara. Berdasarkan UU Nomor 2 Tahun 2011 tentang Partai Politik, sumber dana partai berasal dari tiga sumber yakni, iuran anggota, sumbangan yang sah menurut hukum, dan bantuan APBN/APBD.Jika usulan Mendagri Tito Karnavian disetujui parlemen, maka dana bantuan parpol naik tiga kali lipat. Sebagai contoh, PDIP, yang meraih 25 juta suara sah di Pemilu 2024, saat ini mendapat bantuan Rp25 miliar per tahun. Tiga kali lipat jumlah itu berarti PDIP bisa meraup Rp76 miliar per tahun. Sedangkan, Demokrat yang mengantongi Rp11 miliar dari 11 juta suara sah, nantinya bisa melonjak jadi sekitar Rp33 miliar.Angka ideal untuk dana bantuan parpol memang sejak lama jadi perdebatan. Bahkan, Sekjen Partai Gerindra Ahmad Muzani sempat menyebut, semestinya dana bantuan parpol Rp10 ribu per suara agar partai bisa maksimal menjalankan fungsinya.  Bagaimana mencari angka ideal yang harus digelontorkan negara untuk bantuan dana parpol? Adakah rumusannya? Bagaimana evaluasi terhadap dana bantuan parpol selama ini? Apakah sudah transparan dan akuntabel?Di Ruang Publik KBR, kita akan bahas topik ini bersama Juru Bicara DPP PDI Perjuangan Aryo Seno Bagaskoro dan Peneliti Divisi Hukum, Demokrasi, dan HAM Seknas Forum Indonesia untuk Transparansi Anggaran (FITRA) Siska Barimbing.

Dr. Diwakar Davar and Dr. Jason Luke discuss novel agents in melanoma and other promising new data in the field of immunotherapy that were presented at the 2025 ASCO Annual Meeting. TRANSCRIPT Dr. Diwakar Davar: Hello. My name is Diwakar Davar, and I am welcoming you to the ASCO Daily News Podcast. I'm an associate professor of medicine and the clinical director of the Melanoma and Skin Cancer Program at the University of Pittsburgh's Hillman Cancer Center. Today, I'm joined by my colleague and good friend, Dr. Jason Luke. Dr. Luke is a professor of medicine. He is also the associate director of clinical research and the director of the Phase 1 IDDC Program at the University of Pittsburgh's Hillman Cancer Center. He and I are going to be discussing some key advancements in melanoma and skin cancers that were presented at the 2025 ASCO Annual Meeting. Our full disclosures are available in the transcript of this episode.  Jason, it is great to have you back on the podcast. Dr. Jason Luke: Thanks again so much for the opportunity, and I'm really looking forward to it. Dr. Diwakar Davar: Perfect. So we will go ahead and start talking a little bit about a couple of key abstracts in both the drug development immunotherapy space and the melanoma space. The first couple of abstracts, the first two, will cover melanoma. So, the first is LBA9500, which was essentially the primary results of RELATIVITY-098. RELATIVITY-098 was a phase 3 trial that compared nivolumab plus relatlimab in a fixed-dose combination against nivolumab alone for the adjuvant treatment of resected high-risk disease. Jason, do you want to maybe give us a brief context of what this is? Dr. Jason Luke: Yeah, it's great, thanks. So as almost all listeners, of course, will be aware, the use of anti–PD-1 immunotherapies really revolutionized melanoma oncology over the last 10 to 15 years. And it has become a standard of care in the adjuvant setting as well. But to review, in patients with stage III melanoma, treatment can be targeted towards BRAF with BRAF and MEK combination therapy, where that's relevant, or anti–PD-1 with nivolumab or pembrolizumab are a standard of care. And more recently, we've had the development of neoadjuvant approaches for palpable stage III disease. And in that space, if patients present, based on two different studies, either pembrolizumab or nivolumab plus ipilimumab can be given prior to surgery for somewhere in the 6- to 9-week range. And so all of these therapies have improved time-to-event endpoints, such as relapse-free or event-free survival. It's worth noting, however, that despite those advances, we've had a couple different trials now that have actually failed in this adjuvant setting, most high profile being the CheckMate-915 study, which looked at nivolumab plus ipilimumab and unfortunately was a negative study. So, with RELATIVITY-047, which was the trial of nivolumab plus relatlimab that showed an improvement in progression-free survival for metastatic disease, there's a lot of interest, and we've been awaiting these data for a long time for RELATIVITY-098, which, of course, is this adjuvant trial of LAG-3 blockade with relatlimab plus nivolumab. Dr. Diwakar Davar: Great. So with that, let's briefly discuss the trial design and the results. So this was a randomized, phase 3, blinded study, so double-blinded, so neither the investigators knew what the patients were getting, nor did the patients know what they were getting. The treatment investigational arm was nivolumab plus relatlimab in the fixed-dose combination. So that's the nivolumab standard fixed dose with relatlimab that was FDA approved in RELATIVITY-047. And the control arm was nivolumab by itself. The duration of treatment was 1 year. The patient population consisted of resected high-risk stage III or IV patients. The primary endpoint was investigator-assessed RFS. Stage and geography were the standard stratifying factors, and they were included, and most of the criteria were balanced across both arms. What we know at this point is that the 2-year RFS rate was 64% and 62% in the nivolumab and nivolumab-combination arms, respectively. The 2-year DMFS rate was similarly equivalent: 76% with nivolumab monotherapy, 73% with the combination. And similar to what you had talked about with CheckMate 915, unfortunately, the addition of LAG-3 did not appear to improve the RFS or DMFS compared to control in this patient population. So, tell us a little bit about your take on this and what do you think might be the reasons why this trial was negative? Dr. Jason Luke: It's really unfortunate that we have this negative phase 3 trial. There had been a lot of hope that the combination of nivolumab with relatlimab would be a better tolerated combination that increased the efficacy. So in the metastatic setting, we do have 047, the study that demonstrated nivolumab plus relatlimab, but now we have this negative trial in the adjuvant setting. And so as to why exactly, I think is a complicated scenario. You know, when we look at the hazard ratios for relapse-free survival, the primary endpoint, as well as the secondary endpoints for distant metastasis-free survival, we see that the hazard ratio is approximately 1. So there's basically no difference. And that really suggests that relatlimab in this setting had no impact whatsoever on therapeutic outcomes in terms of efficacy. Now, it's worth noting that there was a biomarker subanalysis that was presented in conjunction with these data that looked at some immunophenotyping, both from circulating T cells, CD8 T cells, as well as from the tumor microenvironment from patients who were treated, both in the previous metastatic trial, the RELATIVITY-047 study, and now in this adjuvant study in the RELATIVITY-098 study. And to briefly summarize those, what was identified was that T cells in advanced melanoma seemed to have higher expression levels of LAG-3 relative to T cells that are circulating in patients that are in the adjuvant setting. In addition to that, there was a suggestion that the magnitude of increase is greater in the advanced setting versus adjuvant. And the overall summary of this is that the suggested rationale for why this was a negative trial may have been that the target of LAG-3 is not expressed as highly in the adjuvant setting as it is in the metastatic setting. And so while the data that were presented, I think, support this kind of an idea, I am a little bit cautious that this is actually the reason for why the trial was negative, however. I would say we're not really sure yet as to why the trial was negative, but the fact that the hazard ratios for the major endpoints were essentially 1 suggests that there was no impact whatsoever from relatlimab. And this really makes one wonder whether or not building on anti–PD-1 in the adjuvant setting is feasible because anti–PD-1 works so well. You would think that even if the levels of LAG-3 expression were slightly different, you would have seen a trend in one direction or another by adding a second drug, relatlimab, in this scenario. So overall, I think it's an unfortunate circumstance that the trial is negative. Clearly there's going to be no role for relatlimab in the adjuvant setting. I think this really makes one wonder about the utility of LAG-3 blockade and how powerful it really can be. I think it's probably worth pointing out there's another adjuvant trial ongoing now of a different PD-1 and LAG-3 combination, and that's cemiplimab plus fianlimab, a LAG-3 antibody that's being dosed from another trial sponsor at a much higher dose, and perhaps that may make some level of difference. But certainly, these are unfortunate results that will not advance the field beyond where we were at already. Dr. Diwakar Davar: And to your point about third-generation checkpoint factors that were negative, I guess it's probably worth noting that a trial that you were involved with, KeyVibe-010, that evaluated the PD-1 TIGIT co-formulation of vibostolimab, MK-4280A, was also, unfortunately, similarly negative. So, to your point, it's not clear that all these third-generation receptors are necessarily going to have the same impact in the adjuvant setting, even if they, you know, for example, like TIGIT, and they sometimes may not even have an effect at all in the advanced cancer setting. So, we'll see what the HARMONY phase 3 trial, that's the Regeneron cemiplimab/fianlimab versus pembrolizumab control with cemiplimab with fianlimab at two different doses, we'll see how that reads out. But certainly, as you've said, LAG-3 does not, unfortunately, appear to have an impact in the adjuvant setting. So let's move on to LBA9501. This is the primary analysis of EORTC-2139-MG or the Columbus-AD trial. This was a randomized trial of encorafenib and binimetinib, which we will abbreviate as enco-bini going forward, compared to placebo in high-risk stage II setting in melanoma in patients with BRAF V600E or K mutant disease. So Jason, you know, you happen to know one or two things about the resected stage II setting, so maybe contextualize the stage II setting for us based on the trials that you've led, KEYNOTE-716, as well as CheckMate-76K, set us up to talk about Columbus-AD. Dr. Jason Luke: Thanks for that introduction, and certainly stage II disease has been something I've worked a lot on. The rationale for that has been that building off of the activity of anti–PD-1 in metastatic melanoma and then seeing the activity in stage III, like we just talked about, it was a curious circumstance that dating back about 7 to 8 years ago, there was no availability to use anti–PD-1 for high-risk stage II patients, even though the risk of recurrence and death from melanoma in the context of stage IIB and IIC melanoma is in fact similar or actually higher than in stage IIIA or IIIB, where anti–PD-1 was approved. And in that context, a couple of different trials that you alluded to, the Keynote-716 study that I led, as well as the CheckMate 76K trial, evaluated pembrolizumab and nivolumab, respectively, showing an improvement in relapse-free and distant metastasis-free survival, and both of those agents have subsequently been approved for use in the adjuvant setting by the US FDA as well as the European Medicines Agency.  So bringing then to this abstract, throughout melanoma oncology, we've seen that the impact of anti–PD-1 immunotherapy versus BRAF and MEK-targeted therapy have had very similar outcomes on a sort of comparison basis, both in frontline metastatic and then in adjuvant setting. So it was a totally reasonable question to ask: Could we use adjuvant BRAF and MEK inhibitor therapy? And I think all of us expected the answer would be yes. As we get into the discussion of the trial, I think the unfortunate circumstance was that the timing of this clinical trial being delayed somewhat, unfortunately, made it very difficult to accrue the trial, and so we're going to have to try to read through the tea leaves sort of, based on only a partially complete data set. Dr. Diwakar Davar: So, in terms of the results, they wanted to enroll 815 patients, they only enrolled 110. The RFS and DMFS were marginally improved in the treatment arm but certainly not significantly, which is not surprising because the trial had only accrued 16% to 18% of its complete accrual. As such, we really can't abstract from the stage III COMBI-AD data to stage II patients. And certainly in this setting, one would argue that the primary treatment options certainly remain either anti–PD-1 monotherapy, either with pembrolizumab or nivolumab, based on 716 or 76K, or potentially active surveillance for the patients who are not inclined to get treated.  Can you tell us a little bit about how you foresee drug development going forward in this space because, you know, for example, with HARMONY, certainly IIC disease is a part of HARMONY. We will know at least a little bit about that in this space. So what do you think about the stage IIB/C patient population? Is this a patient population in which future combinations are going to be helpful, and how would you think about where we can go forward from here? Dr. Jason Luke: It is an unfortunate circumstance that this trial could not be accrued at the pace that was necessary. I think all of us believe that the results would have been positive if they'd been able to accrue the trial. In the preliminary data set that they did disclose of that 110 patients, you know, it's clear there is a difference at a, you know, a landmark at a year. They showed a 16% difference, and that would be in line with what has been seen in stage III. And so, you know, I think it's really kind of too bad. There's really going to be no regulatory approach for this consideration. So using BRAF and MEK inhibition in stage II is not going to be part of standard practice moving into the future. To your point, though, about where will the field go? I think what we're already realizing is that in the adjuvant setting, we're really overtreating the total population. And so beyond merely staging by AJCC criteria, we need to move to biomarker selection to help inform which patients truly need the treatment. And in that regard, I don't think we've crystallized together as a field as yet, but the kinds of things that people are thinking about are the integration of molecular biomarkers like ctDNA. When it's positive, it can be very helpful, but in melanoma, we found that, unfortunately, the rates are quite low, you know, in the 10% to 15% range in the adjuvant setting. So then another consideration would be factors in the primary tumor, such as gene expression profiling or other considerations.  And so I think the future of adjuvant clinical trials will be an integration of both the standard AJCC staging system as well as some kind of overlaid molecular biomarker that helps to enrich for a higher-risk population of patients because on a high level, when you abstract out, it's just clearly the case that we're rather substantially overtreating the totality of the population, especially given that in all of our adjuvant studies to date for anti–PD-1, we have not yet shown that there's an overall survival advantage. And so some are even arguing perhaps we should even reserve treatment until patients progress. I think that's a complicated subject, and standard of care at this point is to offer adjuvant therapy, but certainly a lot more to do because many patients, you know, unfortunately, still do progress and move on to metastatic disease. Dr. Diwakar Davar: Let's transition to Abstract 2508. So we're moving on from the melanoma to the novel immunotherapy abstracts. And this is a very, very, very fascinating drug. It's IMA203. So Abstract 2508 is a phase 1 clinical update of IMA203. IMA203 is an autologous TCR-T construct targeting PRAME in patients with heavily pretreated PD-1-refractory metastatic melanoma. So Jason, in the PD-1 and CTLA-4-refractory settings, treatment options are either autologous TIL, response rate, you know, ballpark 29% to 31%, oncolytic viral therapy, RP1 with nivolumab, ORR about 30-ish percent. So new options are needed. Can you tell us a little bit about IMA203? Perhaps tell us for the audience, what is the difference between a TCR-T and traditional autologous TIL? And a little bit about this drug, IMA203, and how it distinguishes itself from the competing TIL products in the landscape. Dr. Jason Luke: I'm extremely enthusiastic about IMA203. I think that it really has transformative potential based on these results and hopefully from the phase 3 trial that's open to accrual now. So, what is IMA203? We said it's a TCR-T cell product. So what that means is that T cells are removed from a patient, and then they can be transduced through various technologies, but inserted into those T cells, we can then add a T-cell receptor that's very specific to a single antigen, and in this case, it's PRAME. So that then is contrasted quite a bit from the TIL process, which includes a surgical resection of a tumor where T cells are removed, but they're not specific necessarily to the cancer, and they're grown up in the lab and then given to the patient. They're both adoptive cell transfer products, but they're very different. One is genetically modified, and the other one is not. And so the process for generating a TCR-T cell is that patients are required to have a new biomarker that some may not be familiar with, which is HLA profiling. So the T-cell receptor requires matching to the concomitant HLA for which the peptide is bound in. And so the classic one that is used in most oncology practices is A*02:01 because approximately 48% of Caucasians have A*02:01, and the frequency of HLA in other ethnicities starts to become highly variable. But in patients who are identified to have A*02:01 genotype, we can then remove blood via leukapheresis or an apheresis product, and then insert via lentiviral transduction this T-cell receptor targeting PRAME. Patients are then brought back to the hospital where they can receive lymphodepleting chemotherapy and then receive the reinfusion of the TCR-T cells. Again, in contrast with the TIL process, however, these T cells are extremely potent, and we do not need to give high-dose interleukin-2, which is administered in the context of TIL. Given that process, we have this clinical trial in front of us now, and at ASCO, the update was from the phase 1 study, which was looking at IMA203 in an efficacy population of melanoma patients who were refractory at checkpoint blockade and actually multiple lines of therapy. So here, there were 33 patients and a response rate of approximately 50% was observed in this population of patients, notably with a duration of response approximately a year in that treatment group. And I realize that these were heavily pretreated patients who had a range of very high-risk features. And approximately half the population had uveal melanoma, which people may be aware is a generally speaking more difficult-to-treat subtype of melanoma that metastasizes to the liver, which again has been a site of resistance to cancer immunotherapy. So these results are extremely promising. To summarize them from what I said, it's easier to make TCR-T cells because we can remove blood from the patient to transduce the T cells, and we don't have to put them through surgery. We can then infuse them, and based on these results, it looks like the response rate to IMA203 is a little bit more than double what we expect from lifileucel. And then, whereas with lifileucel or TILs, we have to give high-dose IL-2, here we do not have to give high-dose IL-2. And so that's pretty promising. And a clinical trial is ongoing now called the SUPREME phase 3 clinical trial, which is hoping to validate these results in a randomized global study. Dr. Diwakar Davar: Now, one thing that I wanted to go over with you, because you know this trial particularly well, is what you think of the likelihood of success, and then we'll talk a little bit about the trial design. But in your mind, do you think that this is a trial that has got a reasonable likelihood of success, maybe even a high likelihood of success? And maybe let's contextualize that to say an alternative trial, such as, for example, the TebeAM trial, which is essentially a T-cell bispecific targeting GP100. It's being compared against SOC, investigator's choice control, also in a similarly heavily pretreated patient population. Dr. Jason Luke: So both trials, I think, have a strong chance of success. They are very different kinds of agents. And so the CD3 bispecific that you referred to, tebentafusp, likely has an effect of delaying progression, which in patients with advanced disease could have a value that might manifest as overall survival. With TCR-T cells, by contrast, we see a very high response rate with some of the patients going into very durable long-term benefit. And so I do think that the SUPREME clinical trial has a very high chance of success. It will be the first clinical trial in solid tumor oncology randomizing patients to receive a cell therapy as compared with a standard of care. And within that standard of care control arm, TILs are allowed as a treatment. And so it will also be the first study that will compare TCR-T cells against TILs in a randomized phase 3. But going back to the data that we've seen in the phase 1 trial, what we observe is that the duration of response is really connected to the quality of the response, meaning if you have more than a 50% tumor shrinkage, those patients do very, very well. But even in patients who have less than 50% tumor shrinkage, the median progression-free survival right now is about 4.5 months. And again, as we think about trial design, standard of care options for patients who are in this situation are unfortunately very bad. And the progression-free survival in that population is probably more like 2 months. So this is a trial that has a very high likelihood of being positive because the possibility of long-term response is there, but even for patients who don't get a durable response, they're likely going to benefit more than they would have based on standard chemotherapy or retreatment with an anti–PD-1 agent. Dr. Diwakar Davar: Really, a very important trial to enroll, a trial that is first in many ways. First of a new generation of TCR-T agents, first trial to look at cell therapy in the control arm, a new standard of efficacy, but potentially also if this trial is successful, it will also be a new standard of trial conduct, a new kind of trial, of a set of trials that will be done in the second-line immunotherapy-refractory space. So let's pivot to the last trial that we were going to discuss, which was Abstract 2501. Abstract 2501 is a first-in-human phase 1/2 trial evaluating BNT142, which is the first-in-class mRNA-encoded bispecific targeting Claudin-6 and CD3 in patients with Claudin-positive tumors. We'll talk a little bit about this, but maybe let's start by talking a little bit about Claudin-6. So Claudin-6 is a very interesting new target. It's a target that's highly expressed in GI and ovarian tumors. There are a whole plethora of Claudin-6-targeting agents, including T-cell bispecifics and Claudin-6-directed CAR-Ts that are being developed. But BNT142 is novel. It's a novel lipid nanoparticle LNP-encapsulated mRNA. The mRNA encodes an anti–Claudin-6 CD3 bispecific termed RiboMAB-021. And it then is administered to the patient. The BNT142-encoding mRNA LNPs are taken up by the liver and translated into the active drug. So Jason, tell us a little bit about this agent. Why you think it's novel, if you think it's novel, and let's talk a little bit then about the results. Dr. Jason Luke: So I certainly think this is a novel agent, and I think this is just the first of what will probably become a new paradigm in oncology drug development. And so you alluded to this, but just to rehash it quickly, the drug is encoded as genetic information that's placed in the lipid nanoparticle and then is infused into the patient. And after the lipid nanoparticles are taken up by the liver, which is the most common place that LNPs are usually taken up, that genetic material in the mRNA starts to be translated into the actual protein, and that protein is the drug. So this is in vivo generation, so the patient is making their own drug inside their body. I think it's a really, really interesting approach. So for any drug that could be encoded as a genetic sequence, and in this case, it's a bispecific, as you mentioned, CD3-Claudin-6 engager, this could have a tremendous impact on how we think about pharmacology and novel drug development moving into the future in oncology. So I think it's an extremely interesting drug, the like of which we'll probably see only more moving forward. Dr. Diwakar Davar: Let's maybe briefly talk about the results. You know, the patient population was heavily pretreated, 65 or so patients, mostly ovarian cancer. Two-thirds of the patients were ovarian cancer, the rest were germ cell and lung cancer patients. But let's talk a little bit about the efficacy. The disease control rate was about 58% in the phase 1 population as a whole, but 75% in the ovarian patient population. Now tell us a little bit about the interesting things about the drug in terms of the pharmacokinetics, and also then maybe we can pivot to the clinical activity by dose level. Dr. Jason Luke: Well, so they did present in their presentation at ASCO a proportionality showing that as higher doses were administered, that greater amounts of the drug were being made inside the patient. And so that's an interesting observation, and it's an important one, right? Suggesting that the pharmacology that we classically think of by administering drugs by IV, for example, would still be in play. And that did translate into some level of efficacy, particularly at the higher dose levels. Now, the caveat that I'll make a note of is that disease control rate is an endpoint that I think we have to be careful about because what that really means is sometimes a little bit unclear. Sometimes patients have slowly growing tumors and so on and so forth. And the clinical relevance of disease control, if it doesn't last at least 6 months, I think is probably pretty questionable. So I think these are extremely interesting data, and there's some preliminary sense that getting the dose up is going to matter because the treatment responses were mostly observed at the highest dose levels. There's also a caveat, however, that across the field of CD3 bispecific molecules like this, there's been quite a bit of heterogeneity in terms of the response rate, with some of them only really generating stable disease responses and other ones having more robust responses. And so I think this is a really interesting initial foray into this space. My best understanding is this molecule is not moving forward further after this, but I think that this really does set it up to be able to chase after multiple different drug targets on a CD3 bispecific backbone, both in ovarian cancer, but then basically across all of oncology. Dr. Diwakar Davar: Perfect. This is a very new sort of exciting arena where we're going to be looking at, in many ways, these programmable constructs, whether we're looking at in vivo-generated, in this case, a T-cell bispecific, but we've also got newer drugs where we are essentially giving drugs where people are generating in vivo CAR T, and also potentially even in vivo TCR-T. But certainly lots of new excitement around this entire class of drugs. And so, what we'd like to do at this point in time is switch to essentially the fact that we've got a very, very exciting set of data at ASCO 2025. You've heard from Dr. Luke regarding the advances in both early drug development but also in advanced cutaneous melanoma. And Jason, as always, thank you so much for sharing your very valuable and great, fantastic insights with us on the ASCO Daily News Podcast. Dr. Jason Luke: Well, thanks again for the opportunity. Dr. Diwakar Davar: And thank you to our listeners for taking your time to listen today. You will find the links to the abstracts that we discussed today in the transcript of this episode. And finally, if you value the insights that you hear on the ASCO Daily News Podcast, please take a moment to rate, review, and subscribe wherever you get your podcasts. Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Follow today's speakers:    Dr. Diwakar Davar    @diwakardavar    Dr. Jason Luke @jasonlukemd Follow ASCO on social media:     @ASCO on Twitter       ASCO on Bluesky   ASCO on Facebook       ASCO on LinkedIn   Disclosures:     Dr. Diwakar Davar:      Honoraria: Merck, Tesaro, Array BioPharma, Immunocore, Instil Bio, Vedanta Biosciences     Consulting or Advisory Role: Instil Bio, Vedanta Biosciences     Consulting or Advisory Role (Immediate family member): Shionogi     Research Funding: Merck, Checkmate Pharmaceuticals, CellSight Technologies, GSK, Merck, Arvus Biosciences, Arcus Biosciences     Research Funding (Inst.): Zucero Therapeutics     Patents, Royalties, Other Intellectual Property: Application No.: 63/124,231 Title: COMPOSITIONS AND METHODS FOR TREATING CANCER Applicant: University of Pittsburgh–Of the Commonwealth System of Higher Education Inventors: Diwakar Davar Filing Date: December 11, 2020 Country: United States MCC Reference: 10504-059PV1 Your Reference: 05545; and Application No.: 63/208,719 Enteric Microbiotype Signatures of Immune-related Adverse Events and Response in Relation to Anti-PD-1 Immunotherapy     Dr. Jason Luke:     Stock and Other Ownership Interests: Actym Therapeutics, Mavu Pharmaceutical, Pyxis, Alphamab Oncology, Tempest Therapeutics, Kanaph Therapeutics, Onc.AI, Arch Oncology, Stipe, NeoTX     Consulting or Advisory Role: Bristol-Myers Squibb, Merck, EMD Serono, Novartis, 7 Hills Pharma, Janssen, Reflexion Medical, Tempest Therapeutics, Alphamab Oncology, Spring Bank, Abbvie, Astellas Pharma, Bayer, Incyte, Mersana, Partner Therapeutics, Synlogic, Eisai, Werewolf, Ribon Therapeutics, Checkmate Pharmaceuticals, CStone Pharmaceuticals, Nektar, Regeneron, Rubius, Tesaro, Xilio, Xencor, Alnylam, Crown Bioscience, Flame Biosciences, Genentech, Kadmon, KSQ Therapeutics, Immunocore, Inzen, Pfizer, Silicon Therapeutics, TRex Bio, Bright Peak, Onc.AI, STipe, Codiak Biosciences, Day One Therapeutics, Endeavor, Gilead Sciences, Hotspot Therapeutics, SERVIER, STINGthera, Synthekine     Research Funding (Inst.): Merck , Bristol-Myers Squibb, Incyte, Corvus Pharmaceuticals, Abbvie, Macrogenics, Xencor, Array BioPharma, Agios, Astellas Pharma , EMD Serono, Immatics, Kadmon, Moderna Therapeutics, Nektar, Spring bank, Trishula, KAHR Medical, Fstar, Genmab, Ikena Oncology, Numab, Replimmune, Rubius Therapeutics, Synlogic, Takeda, Tizona Therapeutics, Inc., BioNTech AG, Scholar Rock, Next Cure     Patents, Royalties, Other Intellectual Property: Serial #15/612,657 (Cancer Immunotherapy), and Serial #PCT/US18/36052 (Microbiome Biomarkers for Anti-PD-1/PD-L1 Responsiveness: Diagnostic, Prognostic and Therapeutic Uses Thereof)     Travel, Accommodations, Expenses: Bristol-Myers Squibb, Array BioPharma, EMD Serono, Janssen, Merck, Novartis, Reflexion Medical, Mersana, Pyxis, Xilio

Sementara itu, pemirsa, data terbaru dari Badan Pusat Statistik (BPS) menunjukkan angka kemiskinan di Indonesia masih berada di angka 8 persen-an. Angka ini berbeda jauh dengan data versi Bank Dunia yang mencatat tingkat kemiskinan RI mencapai 68,25%.BPS mencatat angka kemiskinan di Indonesia per September 2024 sebesar 8,57%, atau setara dengan 24 juta orang.Perhitungan ini mengacu pada standar nasional, dengan batas garis kemiskinan sekitar Rp1 juta per orang per bulan.Angka dari BPS dinilai jauh lebih rendah dari perkiraan Bank Dunia yang menggunakan standar global paritas daya beli. Namun BPS menegaskan, perhitungan mereka telah disesuaikan dengan kondisi hidup layak di Indonesia.

Beralih ke informasi lain, pemirsa. Berdasarkan data PPATK, perputaran uang judi daring di Indonesia mencapai angka fantastis hingga Rp1.200 triliun di tahun 2025. Pengamat bisnis melihat, angka tersebut dapat menguntungkan Indonesia jika dikelola dengan baik, seperti pembuatan kasino terpusat. Namun, anggota Komisi III DPR RI menilai pembangunan kasino tidak sesuai dengan budaya masyarakat di Indonesia.

Indonesia dulu pernah melegalkan judi demi pembangunan, dan kini muncul lagi usulan legalisasi dari parlemen. Di balik wacana legalisasi judi demi menambah pajak negara, ada fakta mengejutkan: 160 juta transaksi judol, Rp1.200 triliun perputaran uang, dan 71 persen pemainnya dari kalangan ekonomi rendah banyak kalangan dari pengamat mendukung legalisasi judi karena menurutnya ini menjadi pendapatan yang bisa melunasi utang negara. Bagaimana penjelesanya Bagaimana tanggapan MUI terhadap ide legalisasi ini?Wawancara bersama Guru besar Hukum Internasional Universitas Indonesia (UI) - Prof. Hikmahanto Juwana dan Anggota Komisi Fatwa Majelis Ulama Indonesia (MUI) - KH M Nurul Irfan

Pembangunan tahap pertama Kompleks Istana Wakil Presiden (Wapres) di Ibu Kota Nusantara (IKN) Kalimantan Timur kini telah mencapai 43% dan ditargetkan selesai pada Desember 2025. Proyek senilai Rp1,7 triliun ini mencakup pembangunan kantor, kediaman, sekretariat, dan fasilitas pendukung lainnya. Istana ini akan dilengkapi dengan kaca antipeluru yang diimpor dari Amerika Serikat, dengan pemasangan mencapai 22% .

HVAC Masters of the Hustle would like to welcome Chris Badran into the Hot Seat on episode 310. On this episode Jdun dives deep with Chris on RP1 & how imortant is it to have full board. If you are having issues getting apts on the board you dont want to miss this episode as Jdub & Chris drop the GOLD everyone is wanting to hear! Like

Making strides against melanoma: how can medical oncologists and interventional oncologists join forces to deliver smarter, patient-centered care? In this episode of BackTable, Dr. Tyler Sandow, hosts Dr. Sunandana Chandra, medical oncologist at Northwestern, and Dr. Riad Salem, interventional oncologist at Northwestern to discuss the evolving management of advanced melanoma. --- This podcast is supported by an educational grant from Replimune. --- SYNPOSIS The doctors open the episode with an overview of melanoma and recent advances in its treatment, highlighting key trials such as DREAMseq and CheckMate 067. The discussion explores the shift from medical oncologist as solo primary providers to a dynamic, multidisciplinary approach to advanced cancer care—emphasizing cutting-edge treatments like immunotherapy and intratumoral oncolytic viruses. Dr. Salem shares practical insights on the procedural techniques of administering intratumoral oncolytics like Replimune, emphasizing the importance of thorough documentation and patient-centered care. The doctors also provide an overview of the ongoing IGNYTE-3 Trial, a Phase 3 study assessing the safety and efficacy of the oncolytic immunotherapy RP1 in combination with nivolumab for the treatment of advanced melanoma. The episode underscores the transformative potential of innovative melanoma treatments and the crucial role of integrated, team-based approaches in improving cancer patient outcomes. --- TIMESTAMPS 00:00 - Introduction03:48 - The Evolution of Melanoma Treatment: From Chemotherapy to Immunotherapy14:05 - The Role of Oncolytic Viruses in Melanoma Treatment20:14 - Interventional Radiology's Role in Cancer Treatment27:00 - Collaborative Approach to Cancer Care32:53 - Hyper Documentation and Communication Efficiency44:47 - Future of Intratumoral Oncolytics48:10 - Multidisciplinary Approach in Advanced Cancer Management51:46 - Conclusion and Final Thoughts --- RESOURCES DREAMseq Trial: Atkins MB, Lee SJ, Chmielowski B, et al. Combination Dabrafenib and Trametinib Versus Combination Nivolumab and Ipilimumab for Patients With Advanced BRAF-Mutant Melanoma: The DREAMseq Trial-ECOG-ACRIN EA6134. J Clin Oncol. 2023;41(2):186-197. doi:10.1200/JCO.22.01763 CheckMate 067 trial: Wolchok JD, Chiarion-Sileni V, Rutkowski P, et al. Final, 10-Year Outcomes with Nivolumab plus Ipilimumab in Advanced Melanoma. N Engl J Med. 2025;392(1):11-22. doi:10.1056/NEJMoa2407417

In today's episode, supported by Replimune, we had the pleasure of speaking with Anna C. Pavlick, BSN, MSc, DO, MBA, about the use of RP1 plus nivolumab (Opdivo) for the treatment of patients with advanced melanoma. Dr Pavlick is a professor of medicine in the Division of Hematology & Medical Oncology at Weill Cornell Medicine in New York, New York; as well as the founding director of the Cutaneous Oncology Program at Weill Cornell Medicine and NewYork-Presbyterian. In our exclusive interview, Dr Pavlick discussed the rationale for investigating this combination in patients with advanced melanoma who have received prior immune checkpoint inhibition, key efficacy and safety findings from the phase 1/2 IGNYTE trial (NCT03767348), and where the future may be headed regarding the use of oncolytic viruses in melanoma.

Desakan evaluasi hingga menghentikan Makan Bergizi Gratis (MBG) terus mengemuka, menyusul terungkapnya sederet masalah dalam program unggulan Prabowo-Gibran ini. Yang terus berulang adalah kasus pelajar keracunan usai menyantap menu MBG, di antaranya terjadi di Cianjur, Jawa Barat, Sukoharjo, Jawa Tengah, hingga Bombana, Sulawesi Tenggara. Di Cianjur, bahkan, kasus itu ditetapkan sebagai Kejadian Luar Biasa (KLB).Komentar Kepala Badan Gizi Nasional (BGN) Dadan Hindayana makin menyulut kemarahan publik, karena menganggap kasus keracunan masih terbilang kecil, yakni 0,5 persen dari total 2 juta penerima manfaat MBG.Pertengahan April lalu, program ini juga digoyang kasus tutupnya dapur MBG di Kalibata, Jakarta, karena ada tunggakan pembayaran hampir Rp1 miliar.Program MBG memang mendapat banyak sorotan karena menyedot anggaran negara yang sangat besar. Tak sedikit yang mendukung program ini, tetapi sangsi dengan pengelolaan dan implementasinya.Sejumlah lembaga melakukan pemantauan sejak kick off MBG 6 Januari 2025. Apa saja temuan dan evaluasinya? Apakah program ini harus dihentikan atau ditunda?Ruang Publik akan membahasnya bersama Founder dan CEO Center for Indonesia's Strategic Development Initiatives (CISDI), Diah Satyani Saminarsih dan Staf Divisi Riset & Advokasi Indonesia Corruption Watch (ICW), Eva Nurcahyani.

Pusat Pelaporan dan Analisis Transaksi Keuangan (PPATK) memaparkan, perputaran uang dari aktivitas judi online (judol) 2025 mencapai Rp1.200 triliun. Dari angka itu, Polri dan Kementeri dan Komunikasi dan Digital (Komdigi) dapat menekan hingga Rp500 triliun.

Seorang kasir perusahaan perkebunan kelapa sawit nekad mencuri uang gaji karyawan lebih dari Rp1 miliar di Pekanbaru, Riau. Uang hasil kejahatan ini digunakan untuk membayar utang dan bermain judi online.

SILABUSPPATK ungkap perputaran uang judi online pada 2025 diperkirakan tembus Rp1.200 trilyun, apa yang harus dilakukan? bersama:Pakar hukum pidana Univ Tarumanegara, Heri FirmansyahSosiolog Universitas Katolik (Unika) Soegijapranata Semarang, Hermawan Pancasiwi

Indeks Harga Saham Gabungan (IHSG) pada pembukaan perdagangan setelah libur panjang Lebaran, Selasa, 8 April 2025, langsung ambruk ke posisi 5.914,28.Mengacu data RTI yang terekam hingga pukul 09.05 WIB, IHSG tercatat jatuh ke level 5.912,06 atau turun sebanyak 598,55 poin setara 9,19 persen.Hal ini membuat pasar saham Indonesia langsung trading halt, yakni penghentian sementara perdagangan saham yang terjadi ketika IHSG mengalami penurunan yang signifikan.Adapun sebanyak 552 saham emiten melemah pada perdagangan pagi ini. Sementara, hanya sembilan saham yang berhasil menguat dan 65 saham yang stagnan.Untuk sementara, total transaksi yang tercatat hingga pukul 09.05 WIB sebanyak Rp1,92 triliun dengan total saham yang diperdagangkan 1,59 miliar saham.

Welcome to this exciting episode of The Edge of Show, your gateway to the Web3 revolution! Join us as we dive deep into the latest innovations in blockchain, cryptocurrency, NFTs, and the metaverse, featuring special guests. In this episode, we explore the groundbreaking launch of the world's first 3D browser with RP1, designed to revolutionize how we interact with the digital world. Sean Mann and Dean Abramson share insights on their journey from vision to reality, discussing the technology that allows for unprecedented scalability and user experience in the metaverse.Additionally, we also sat with Yumin Xia, co-founder and CTO of Galxe, to talk about their viral reward platform and the challenges of user retention in the crypto space. Yimin shared insights on building a new blockchain, GravityChain, aimed at simplifying user interactions across multiple blockchains.Finally, Will Hennessey from Alchemy discusses their recent $5 million initiative to onboard new users into crypto through account abstraction and rollups, making the user experience seamless and accessible.Tune in for an engaging discussion filled with insights from industry leaders and learn how you can get involved in the future of Web3! Support us through our Sponsors! ☕

Bank Indonesia mencatat kredit konsumsi tumbuh 9,4% per Februari 2025, mencapai Rp2.208,5 triliun. Kredit multiguna menjadi pendorong utama dengan Rp1.265 triliun, diikuti KPR Rp799,8 triliun, dan kredit kendaraan Rp143,1 triliun. Secara keseluruhan, kredit perbankan naik 9% menjadi Rp7.684 triliun.

Kasus dugaan korupsi yang menyeret sejumlah petinggi Pertamina membuat geger masyarakat. Bukan hanya tuduhan Pertamax oplosannya, namun juga nilai kerugian yang ditaksir mencapai hampir Rp1.000 triliun. Kasus ini menjadi kasus korupsi terbesar dari jumlah kerugian yang berhasil dibongkar aparat.Walau pemberantasan korupsi terus dilakukan dan fakta integritas serta antikorupsi sudah ditandatangani, nyatanya masih saja banyak pejabat di republik ini yang terjerat korupsi. Bahkan, nilai korupsi semakin besar dari waktu ke waktu, dari puluhan hingga ratusan triliun rupiah.Apa yang salah dengan negara ini ketika budaya korupsi terus merajalela? Dan, mengapa koruptor belum ada dihukum mati?

This week, we were all over the place with a bunch of different designs and experiments. After last week's analysis of the TLV320DAC3100, we made some updates to the design and re-booked prototype PCBs. We also designed a triple-matrix bonnet: with our latest work on getting HUB75 RGB matrices working on the Raspberry Pi 5, we can now do matrix control on the latest Pi 5 chip. But we're limited by the RP1 chip, so to get big displays going, we'll need multiple strands—these don't use significantly more bandwidth because half of the pins are shared. Finally, we ended the week by getting another older prototype working: the SAM-M8Q is an entry-level all-in-one GPS from u-blox. It comes with both UART and I2C interfaces, plus a built-in antenna, so it's ready to go out of the box. The NMEA interface is trivial, but we also wanted to try out the UBX interface, and thankfully, Claude 3.7 was able to vibe-code it for us in a jiffy.

Presiden AS Donald Trump siap sampaikan pidato di hadapan Kongres hari Selasa (4/3), di mana isu Gaza dan Ukraina diperkirakan akan disinggung. Sementara di Indonesia, Presiden Prabowo Subianto akan menggelontorkan Rp1-2 triliun per bulan untuk program Makan Bergizi Gratis mulai Maret.

Charlie, Ted, and Rony welcome Sean Mann, CEO of RP1, whose Metaverse browser can support hundreds of thousands of unique users in a spatial environment. It's earning week in the tech world and the outlook for 2025, after two years of hypergrowth, is downright conservative. Love for Meta's money printing machine continued, despite continued losses on its Metaverse ambitions. Apple's discontinuing AR glasses. Or are they? And Alexa is back. Using RP1's browser, users can share spatial environments, including 1:1 maps of the physical world, on any browser, including VR. Charlie says the MR demo of RP1 that he showed him on Thursday was the most like the mixed reality described in "Snow Crash" he has ever seen. Thank you to our sponsor, Zappar!Don't forget to like, share, and follow for more! Follow us on all socials @ThisWeekInXR!https://linktr.ee/thisweekinxr Hosted on Acast. See acast.com/privacy for more information.

This week's EYE ON NPI is an EYE ON A PI - it's the Raspberry Pi Compute Module 5 (https://www.digikey.com/en/product-highlight/r/raspberry-pi/raspberry-pi-compute-module-5), the latest update to the easily embeddable mini modules that make industrial developers happy by giving them all the power of a Pi 5 in a ready-to-go pluggable solution. The Raspberry Pi computer launched with the goal of bringing low cost computing to the education market (https://www.bbc.co.uk/blogs/thereporters/rorycellanjones/2011/05/a_15_computer_to_inspire_young.html) and through the Pi Foundation (https://www.raspberrypi.org/) they still have that charitable goal (https://static.raspberrypi.org/files/about/RaspberryPiFoundationStrategy2025.pdf) while also spinning off the manufacturing/sales company into the Trading Company which went public this year (https://www.raspberrypi.org/blog/what-would-an-ipo-mean-for-the-raspberry-pi-foundation/). The first few Raspberry Pi computers were 'all in one' style (https://www.adafruit.com/product/1344), with power, GPIO, Video and Audio output, USB, Ethernet, and Micro SD card storage (https://raspi.tv/2018/new-raspberry-pi-family-photo-including-pi3a-plus-zero-wh). Eventually enough folks asked for an enclosure-friendly version that would allow an "I/O" board to be designed with the ports in a different arrangement - the big-sized-Pis have them arrayed over 3 sides. To solve this conundrum, and to satisfy the growing industrial/commercial market, the Pi engineers designed the Compute Module 1 which is still available (https://www.raspberrypi.com/products/compute-module-1/). This clever SODIMM packaged board has all the GPIO and peripheral pins on a plug-in connector so you can slot it into an existing design securely and easily - SODIMM sockets (https://www.digikey.com/short/rz9cdjrn) come both vertical and horizontal. This was later updated to the CM3 and CM3+ (https://www.digikey.com/en/products/detail/raspberry-pi/SC0149/9866293) which was on par with the Pi 3 instead of the Pi 1, with significantly higher computational power. However, perhaps because they wanted a more compact module, or to support high-frequency signals better, the next generation of Compute Module 4's (https://www.digikey.com/short/wffzdn0b) came in a flat rectangular shape with dual 100-pin Hirose contacts. (https://www.digikey.com/short/5m8djf0t) Another nice thing that happened with the CM4 is it became available in dozens of configurations: 1/2/4/8 GB RAM, SD or 8/16/32GB MMC, and with or without WiFi/BLE/BT. This allowed commercial users to go with the 'lowest cost option' needed to fulfill their requirements - whereas the Pi 4 comes in only 3 or 4 RAM options (https://www.digikey.com/short/4pn5vw24). The ready-to-go software - no kernel compiling or OpenWRT configuration required! Long-term hardware support and low prices pushed the CM4 into more and more designs. Which brings us to the NPI of the week, the Compute Module 5 (https://www.digikey.com/en/product-highlight/r/raspberry-pi/raspberry-pi-compute-module-5)! The CM5 is a big upgrade, with quad A76s at 2.4GHz for a 2x computing upgrade, increased RAM options of up to 16G, increased MMC option of 64GB, USB 3.0 ports, PCIe and RP1 hardware interfacing with PIO support (https://www.raspberrypi.com/news/piolib-a-userspace-library-for-pio-control/). If you have an existing CM4 design, you can easily upgrade or update to the new hotness. If you're new to integrating Raspberry pi, then while you may think of the Pi as a hobby/school computer, that isn't necessarily true anymore with 72% of Pi computers sold going into commercial/industrial use (https://investors.raspberrypi.com/ipo/documents/1). That means you can be confident that you'll get consistent pricing and availability for a long time so that you can work on designing the rest of your product for the CM series to plug into. And like the CM4, the CM5 is available in a variety of configurations and prices, from $45 to $135. Raspberry Pi Compute Module 5's are currently only available for pre-order (https://www.digikey.com/en/product-highlight/r/raspberry-pi/raspberry-pi-compute-module-5) , with estimated ship times in Q1 of 2025 to DigiKey - and the moment DigiKey gets some in stock, they'll ship your pre-order instantly so you can get integrating with the Pi ecosystem the very next day. Don't wait till release day because they'll sell out instantly! Instead, when you pre-order from DigiKey, your order goes into a queue and you'll get first-come-first-served prioritization. See more on DigiKey https://www.digikey.com/short/47t12drj

Ladyada tasked Jepler with exploring the new libPIO for Raspberry Pi 5 computers: this gives us access to the RP1 chip so that we can run custom PIO state machines on the GPIO pins. A common use case is NeoPixels, because of the tight timing requirements of the WS281x LEDs. Here is our first light test that shows it is possible... Visit the Adafruit shop online - http://www.adafruit.com ----------------------------------------- LIVE CHAT IS HERE! http://adafru.it/discord Subscribe to Adafruit on YouTube: http://adafru.it/subscribe New tutorials on the Adafruit Learning System: http://learn.adafruit.com/ ----------------------------------------- #raspberrypi #adafruit #pio

Hot off the PIO-presses, our resident Jepler created a Python binding for the Raspberry Pi 5 that lets us use the RP1 chip (https://www.raspberrypi.com/news/rp1-the-silicon-controlling-raspberry-pi-5-i-o-designed-here-at-raspberry-pi/) on the 5/500 series boards to drive Neopixels using PIO. This is great because we can now use Neopixels (https://www.adafruit.com/category/168) and friends on the latest Pi boards, and we can use any pin because PIO is not limited by underlying peripherals. You do need the latest kernel and firmware, so it is not quite ready for prime-time, but once piolib (https://github.com/raspberrypi/utils/tree/master/piolib) is more readily available, we'll be able to have folks test this out. Visit the Adafruit shop online - http://www.adafruit.com ----------------------------------------- LIVE CHAT IS HERE! http://adafru.it/discord Subscribe to Adafruit on YouTube: http://adafru.it/subscribe New tutorials on the Adafruit Learning System: http://learn.adafruit.com/ ----------------------------------------- #raspberrypi #NeoPixels #Python

Mafia Kasus, Bukti Keadilan Kian Tergerus Oleh. Dyah Pitaloka(Tim Penulis Inti NarasiPost.Com) Voice over talent: Dewi Nasjag NarasiPost.Com-Dilansir dari metro.tempo.co, Kejaksaan Agung menetapkan Zarof Ricar, mantan pejabat MA, sebagai tersangka kasus suap terkait perkara Gregorius Ronald Tannur. Zarof ditangkap sehari sebelumnya di Bali dan diduga menjadi perantara antara pengacara Tannur, Lisa Rachmat, dengan hakim. Lisa menjanjikan Rp5 miliar kepada hakim, sementara Zarof menerima Rp1 miliar. Naskah selengkapnya: ⁠https://narasipost.com/opini/11/2024/mafia-kasus-bukti-keadilan-kian-tergerus/ Terimakasih buat kalian yang sudah mendengarkan podcast ini, Follow us on: instagram: http://instagram.com/narasipost Facebook: https://www.facebook.com/narasi.post.9 Fanpage: Https://www.facebook.com/pg/narasipostmedia/posts/ Twitter: Http://twitter.com/narasipostx

Kabinet Gemoy, Beban APBN Gemoy Oleh. Vega Rahmatika Fahra, S.H.(Kontributor NarasiPost.Com) Voice over talent: Dewi Nasjag NarasiPost.Com-Pemerintahan baru yang dipimpin oleh Presiden Prabowo Subianto dan Wakil Presiden Gibran Rakabuming Raka menimbulkan banyak perhatian dari masyarakat, khususnya terkait jumlah menteri dan wakil menteri yang ditunjuk. Dengan total 49 menteri dan 59 wakil menteri, kabinet ini disebut-sebut sebagai kabinet gemoy (gemuk) yang berpotensi menguras Anggaran Pendapatan dan Belanja Negara (APBN) hingga Rp1,95 triliun. Kenaikan anggaran yang signifikan ini menimbulkan berbagai pertanyaan tentang efisiensi dan prioritas penggunaan anggaran pemerintah. (cnnindonesia.com, 17-10-2024) Naskah selengkapnya: ⁠https://narasipost.com/opini/10/2024/kabinet-gemoy-beban-apbn-gemoy/ Terimakasih buat kalian yang sudah mendengarkan podcast ini, Follow us on: instagram: http://instagram.com/narasipost Facebook: https://www.facebook.com/narasi.post.9 Fanpage: Https://www.facebook.com/pg/narasipostmedia/posts/ Twitter: Http://twitter.com/narasipostx

Wacana penyesuaian tarif KRL atau commuter line Jabodetabek kembali mengemuka. Pemerintah ingin mengubah skema subsidi KRL menjadi berbasis Nomor Induk Kependudukan (NIK). Wacana ini mengundang kritik karena tarif bakal naik untuk kalangan tertentu. Padahal, daya beli masyarakat tengah melemah seiring lesunya ekonomi. Apalagi, layanan KRL juga dinilai belum optimal. Kalangan yang pro memandang wacana penyesuaian tarif KRL sebagai hal wajar. Sebab, sejak 2016 tarif dasar KRL belum berubah, yakni Rp3.000 untuk 25 km pertama, dan penambahan Rp1.000 untuk 10 km berikutnya. Bagaimana menjembatani pro-kontra ini? Apakah tarif KRL perlu dinaikkan? Tepatkah penerapan skema subsidi transportasi berbasis NIK? Kita bincangkan bersama Wakil Ketua Pemberdayaan dan Pengembangan Wilayah Masyarakat Transportasi Indonesia (MTI) Pusat, Djoko Setijowarno dan Jubir KRLMania Gusti Raganata. *Kami ingin mendengar saran dan komentar kamu terkait podcast yang baru saja kamu simak, melalui surel ke podcast@kbrprime.id

Banyak orang percaya investasi emas bisa jadi aset aman atau safe haven, yang melindungi saat aset lain berfluktuasi. Ternyata, logam mulia ini tidak hanya sebagai penyimpan nilai, tetapi juga memberikan return. Apalagi dengan kondisi dunia yang masih tidak pasti, nilai emas semakin tinggi. Jika dibandingkan dengan aset investasi lainnya dalam setahun terakhir, kinerja emas justru unggul. Misalnya, harga beli emas Treasury sudah naik 29%, dan per 28 Mei 2024 mencapai Rp1.257.706 per gram. Apakah ini pertama kalinya emas unggul dari aset lain atau sebelumnya juga pernah seperti ini? Temukan jawabannya di Podcast Bareksa Insight Eps.22 kali ini bersama Andreas Santoso, CEO Treasury. Install sekarang! https://bareksa.onelink.me/bLEI/YTBareksa

Dr. Diwakar Davar and Dr. Jason Luke discuss advances in the neoadjuvant immunotherapy space that were presented at the 2024 ASCO Annual Meeting, including promising outcomes in high-risk melanoma from the NADINA trial, as well as other new treatment options for patients with advanced cancers.    TRANSCRIPT Dr. Diwakar Davar: Hello and welcome to the ASCO Daily News Podcast. I'm your guest host, Dr. Diwakar Davar, and I am an associate professor of medicine and the clinical director of the Melanoma Skin Cancer Program at the University of Pittsburgh's Hillman Cancer Center. I am delighted to have my colleague and friend Dr. Jason Luke on the podcast today to discuss key late-breaking abstracts and advances in immunotherapy that were presented at the 2024 ASCO Annual Meeting. Dr. Luke is an associate professor of medicine, the associate director of clinical research, and the director of the Cancer Immunotherapeutic Center at the University of Pittsburgh Hillman Cancer Center.   You will find our full disclosures in the transcript of this episode.  Jason, it's always a pleasure to hear your insights on the key trials in these spaces and to have you back as a guest on this podcast that highlights some of the work, especially advances, that were just presented. Dr. Jason Luke: Well, thanks very much for the invitation. I always love joining the podcast. Dr. Diwakar Davar: We'll start very quickly by talking about some advances and really interesting things that happened both in the context of melanoma but also in immunotherapy in general. And we'll start with what I think was certainly one highlight for me, which was LBA2, the late-breaking abstract on the NADINA trial. It was featured in the Plenary Session, and in this abstract, Dr. Christian Blank and colleagues reported on the results of this phase 3 trial of neoadjuvant ipi-nivo. This is the flipped dose of ipi1/nivo3 versus adjuvant nivolumab in PD-1 naive, macroscopic, resectable, high-risk stage 3 melanoma.  By way of background, neoadjuvant immunotherapy for those listening is an area of increasing interest for drug developers and development for both approved and novel agents. Neoadjuvant immunotherapy has been studied with multiple approved agents, including PD-1 monotherapy, PD-1 LAG-3, PD-1 CTLA-4, T-VEC, as well as investigational agents and multiple randomized and non-randomized studies. The benchmark pathologic response rates with these agents range from 17% PCR with PD-1 monotherapy, 45% to 55% PCR with PD-1 CTLA-4 combination therapy, and slightly higher 57% PCR with PD-1 LAG-3 has recently reported by Dr. Rodabe Amaria from MD Anderson. However, as we embark on phase 3 comparisons for various neoadjuvant compared to adjuvant immunotherapy trials and combinations, we're increasingly moving towards event-free survival as the primary endpoint for neoadjuvant versus adjuvant studies. And this was most recently studied in the context of SWOG S1801, a study that was led by Dr. Sapna Patel.  So, Jason, before we start on NADINA, can you briefly summarize the SWOG S1801 trial and the event-free survival statistic reported by Dr. Patel and her colleagues? Dr. Jason Luke: Well, absolutely. And these data were reported at ESMO about two years ago and then in the New England Journal last year. The S1801 study answered a very simple question: What would happen if you took three of the doses of standard adjuvant therapy with pembrolizumab and moved them prior to surgery? And on a high level, the study is as simple as that. And many of us were somewhat skeptical of this trial design because we thought that just moving the doses earlier may not actually have a major impact.  In the study, you alluded to the event-free survival statistic, and that alludes to what was considered an event. And so, without reading all of it, there were several different aspects that were included in terms of time, based on the date of randomization until the first of a series of events, such as disease progression, toxicity from treatment, if the patient was unable to go to surgery or had surgical complications, or if they had delay in starting the adjuvant therapy due to toxicity, and obviously, recurrence of melanoma or death from any cause. In that context, merely moving the 3 doses of pembrolizumab to the neoadjuvant setting saw an improvement in this two-year event free survival to 72% for the neoadjuvant therapy compared to 49% for the adjuvant therapy. That was quite an outstanding change. And again, noting the power of neoadjuvant treatment, really dictating the impact of anti PD-1, again, just with 3 doses moving from adjuvant into the neoadjuvant setting, and I think all of us were somewhat surprised to see that magnitude of a benefit. But it set up the current study very well, where we now look at combination therapy. Dr. Diwakar Davar: So let's move on to the phase 3 NADINA trial. Do you want to perhaps discuss the study design, particularly focusing on the EFS primary endpoint and maybe also touching on the different schedules? So, SWOG S1801 was a neoadjuvant study of 3 cycles of pembrolizumab and how did that compare and contrast to the neoadjuvant combination that was studied in NADINA? Dr. Jason Luke: Well, as you alluded to, NADINA investigated the regimen of nivolumab plus ipilimumab and compared that against adjuvant therapy with nivolumab alone. So, in the study, as you alluded, the dose and schedule of the two drugs used was nivolumab at 3 milligrams per kilogram, and ipilimumab with 1 milligram per kilogram. That was based on a series of signal finding and safety studies that had been previously done by the same group of authors identifying that as the optimal treatment regimen. And it's worth noting that's slightly different than the labeled indication that's generally used for those same drugs for metastatic melanoma, albeit that the NCCN also endorses this schedule. So, in the trial, 423 patients were randomized, 1:1 to receive either neoadjuvant therapy with those 2 doses of nivolumab plus ipilimumab as compared with standard adjuvant therapy with nivolumab following surgery.   Now, one interesting tweak was that there was an adaptive nature to the study, meaning that patients had a fiducial placed at the index lymph node, and after the neoadjuvant therapy in that arm, that lymph node was removed. And if the patient had a major pathological response, they did not go on to receive the adjuvant portion of the treatment. So it was adaptive because those patients who did very well to the neoadjuvant did not require the adjuvant portion. And in those patients who did not achieve a major pathological response, they could go on to have the adjuvant therapy. And that also included the BRAF therapy for those whose tumors were BRAF mutants.  It's also worth pointing out that the definition of event free survival was slightly different than in the S1801 study that was alluded to just a second ago. And here, EFS was defined from the date of randomization until progression due to melanoma or due to treatment. So that's slightly different than the definition in the S1801 trial. So, a somewhat complicated study, but I really applaud the authors because I think this study does mirror what we would likely be doing in actual clinical practice.  Dr. Diwakar Davar: So, just to briefly summarize the efficacy, and then to get your comments on this, the path response, the PCR rate was 47%. The major pathologic response rate, which is the proportion of patients with between 0% to 1/10% of residual viable tumors, was about 12%. And for a major pathologic response rate of 0% to 10% of 59%. And then the rest of the patients had either pathologic partial response, which was 10% to 50%, or pathologic non response or 50% or greater residual viable tumor, all assessed using central pathology grades. The one year RFS was 95% in the FDR patient population versus 76% in the pathologic partial response patient population, 57% in the pathologic non response patient population. So how do you view these results? Can you context the FDR rates and the EFS rates from NADINA relative to nivo-rela and also potentially SWOG 1801? Dr. Jason Luke: Well, I think these are very exciting results. I think that for those of us that have been following the field closely, they're actually not especially surprising because they mirror several studies that have come before them. When we put them in context with other studies, we see that these rates of major pathological response are consistent with what we've seen in phase 2 studies. They're relatively similar. Or I should say that the results from nivolumab and relatlimab, which was also pursued in a phase 2 study of somewhat similar design, are somewhat similar to this. So, combination immunotherapy does look to deliver a higher major pathological response than pembrolizumab alone, as was known in S1801. Which of course, the caveat being is these are cross control comparisons that we need to be careful about. So I think all of these are active regimens, and I think adding a second agent does appear to enhance the major pathologic response rates. When we look at the event free survival, we see something similar, which is that numerically it looks to be that combination immunotherapy delivers a higher event free survival rate. And that looks to be rather meaningful given the difference in the hazard ratios that were observed between these various studies. And here in the NADINA study, we see that 0.3 hazard ratio for EFS is just extremely impressive.  So the abstract then, from ourselves, out of these specific studies, what does this mean more broadly in the real world, where patients exist and the rest of the landscape for clinical trials? I think we can't take enough time to stop for a second and just think about what a revolution we've come forward in with immune checkpoint blockade and melanoma. When I started my career, now, more than 15 years ago, melanoma was the cancer that made cancer bad. And now here we say, in the highest risk of perioperative patients, we can deliver 2 doses of nivolumab and ipilimumab, and essentially half of the patients then don't need to go on, and more than half the patients don't need to go on to have a full surgery and don't need adjuvant therapy. And from what we could tell of a very, very low risk of every heavy recurrence of melanoma. Of course, there's the other half of patients where we still need to do better, but these are just fantastic results and I think highly meaningful for patients.   In the context of ongoing clinical trials, another abstract that was presented during the meeting was the update to the individualized neoantigen therapy, or V940 with pembrolizumab or against pembrolizumab alone. That's the KEYNOTE-942 study. In that study, they presented updated data at two and a half years for relapse free survival, noting a 75% rate without relapse. So those results are also highly intriguing. And these are in a similar population of very high risk patients. And so I think most of us believe that neoadjuvant therapy with this study in NADINA is now confirmed as the priority approach for patients who present with high-risk stage 3 disease. So that would be bulky disease picked up on a scan or palpable in a clinic. I think essentially all of us now believe patients should get preoperative immunotherapy. We can debate which approach to take, and it may vary by an individual patient's ability to tolerate toxicity, because, of course, multi agent immunotherapy does have increased toxicity relative to anti PD-1 alone. But we'll have to wait now for the full phase 3 results from the V940 individualized neoantigen therapy. And if those come forward, that will be an extremely attractive approach to think about for patients who did not achieve a major pathological response to neoadjuvant therapy, as well as of course to the other populations of patients with melanoma where we otherwise currently give adjuvant therapy stage 2B all the way through stage 4 resected. It's an amazing time to think about perioperative therapy in melanoma. Dr. Diwakar Davar: So this is clearly outstanding data, outstanding news. Congratulations to the investigators for really doing what is an investigative initiated trial conducted across multiple continents with a huge sample size. So this clearly appears to be, at this point in time at least, a de facto standard. But is this going to be FDA-approved, guideline-approved, or is it possible in your mind? Dr. Jason Luke: Well, that's an interesting question. This study was not designed with the intent to necessarily try to register this treatment regimen with the FDA. One would have to take a step back and say, with how powerful these data appear, it sort of seemed like it would be too bad if that doesn't happen. But all the same, I think the community and those of us who participate in guideline recommendations are fully supportive of this. So, I think we will see this move into compendium listings that support insurance approval, I think, very, very quickly. So, whether or not this actually becomes formally FDA approved or is in the guidelines, I think this should become the standard approach that is considered for patients, again presenting with high-risk stage 3 disease.  Dr. Diwakar Davar: Fantastic. So now we're going to go in and talk about a slightly different drug, but also from the melanoma context, and that is the safety and efficacy of RP1 with nivolumab in the context of patients with melanoma who are PD-1 failures. So, this is Abstract 9517. And in this abstract, our academic colleagues essentially talked about these data, and we'll start by describing what RP1 is. RP1 essentially is a HSV-1 based oncolytic immunotherapy. And RP1 expresses GM-CSF as well as a fusogenic protein, GALV-GP-R-. And in this abstract, Dr. Michael Wong from MD Anderson and colleagues are reporting the results of IGNYTE, which is a phase I trial of intratumoral RP1 co-administered with systemic nivolumab in patients with advanced metastatic treatment refractory cutaneous melanoma. And the data presented in this abstract represents data from a registration directed, abbreviated as RD, registration directed cohort of RP1 plus nivolumab in PD-1 refractory melanoma. So, let's start with the description of the cohort.  Dr. Jason Luke: Right. So, in this study, there were a total of 156 patients who were presented, and that included an initial safety and dose finding group of 16, as well as the RD cohort, as you noted, of 140 patients. And it's important to point out that this was a cohort that was selected for a very strict definition of progression on anti PD-1, or a combination immunotherapy as their immediately prior treatment. So, all of the patients in the cohort had exposure to anti PD-1, and 46% of them had anti PD-1 plus anti CTLA4, nivolumab and ipilimumab as their immediately prior therapy. This was also a group of relatively high-risk patients when one considers stage. So, within the stage 4 population, the entry here included 51% who had stage M1B, C, and D melanoma. And that is worth pointing out because this is an injectable therapy. So, trials like this in the past have tended to be biased towards earlier stage, unresectable or metastatic melanoma, meaning stage 3B, 3C, 3D and then stage 4m1a. Again, to emphasize the point here, these were pretreated patients who had a strict definition of anti PD-1 resistance, and over half of them, in fact, had high-risk visceral metastatic disease.  In that context, it's very interesting to observe that the overall response rate was described in the total population, as 31%, and that included 12% who achieved complete response. And so, again, to make sure it's clear, we're talking about a treatment where the oncolytic virus is injected into one or multiple sites of recurrent disease, and then the patients administer nivolumab as per standard. And so, I think these data are quite intriguing. Again, such a high- risk population and their maturity now, with a follow-up of over a year, I think, makes this look to be a very interesting treatment option.  Dr. Diwakar Davar: I guess on that topic of mature follow-up, it probably would be important for us to inform our audience that the top line data for the primary analysis was actually just released, I think, earlier today, and wherein the central confirmed objective response rate was 34% by modified RECIST and 33% by RECIST, clearly indicating that these responses, as you noted, very treatment refractory patient population, these responses were clearly very durable. So, you mentioned that there were responses seen in uninjected visceral lesions, responses seen in both PD-1 and PD-1 CTLA-4 refractory patients. Can you talk a little bit about the response rate in these high-risk subgroups, the uninjected visceral lesions, the patients who had both combination checkpoint and epidural refractory response rate by primary PD-1 resistance.  Dr. Jason Luke: Sure. You know, I think, again, to emphasize this point in the study, we saw that there were responses in the non-injected lesions, and I think it's really important to emphasize that. Some have referred to this as a putative abscopal like effect, similar to what is described in radiation. But it implies that local treatment with the oncolytic virus is triggering a systemic immune response. In the higher risk patient population, we'll note that whereas the overall response rate in PD-1 refractory patients was 34%, in the combination of PD-1 and CTLA-4 refractory patients, the response rate was 26%. So, [this is] still very good. And when we looked at that split by stage, as I alluded to before, in the population of patients that had, what you might call earlier unresectable diseases, so 3B through 4A, the response rate was 38%, and in the stage 4 M1b through M1d, it was 25%. So slightly lower, but still very good. And that would be as expected, because, of course, the patients with visceral metastatic disease have more advanced disease, but those response rates look quite good. Again, looking at the combination refractory population as well as the more high-risk disease. Dr. Diwakar Davar: So, clearly, these are very promising data and exciting times for multiple investigators in the field and the company, Replimune, as well. So, what are the next steps? I believe that a registration trial is planned, essentially, looking at this with the goal of trying to get this combination registered. Can you tell us a little bit about IGNYTE-3, the trial design, the control arm, and what you foresee this trial doing over the next couple of years?  Dr. Jason Luke: So, as this agent has been maturing, it's worth pointing out that the company that makes this molecule, called RP1, but I guess now we'll have to get used to this name vusolimogene oderparepvec as the actual scientific term, they have been having ongoing discussions with the FDA, and there is the potential that this agent could come forward on an accelerated path prior to the results being released from a phase 3 trial. That being said, the phase 3 confirmatory study, which is called the IGNYTE-3 study, is in the process of being launched now. And that's a study investigating this molecule in combination with nivolumab, as was alluded to earlier, and a randomized phase 3 design, where that combination is compared with a physician's choice, essentially a chemotherapy-based option.   In that study, it will be 400 patients with stage 3B through stage 4; patients will have progressed on anti PD-1, either as a combination or in sequence, and then come on the study to be randomized to either vusolimogene oderparepvec plus nivolumab versus that physician's choice. And the physician's choice includes chemotherapy agents, but also nivolumab plus relatlimab as another option, or an anti PD-1 monotherapy, if that's deemed to be a reasonable option by the treating investigator. And the primary endpoint of that study is overall survival. And unfortunately, in this highly refractory patient population, that's something that may not take long to identify with key secondary endpoints of progression free survival, as well as overall response rate. I'm quite enthusiastic about this study, given these data, which have now been centrally confirmed as you alluded to before. I think this is a very exciting area of investigation and really crossing my fingers that this may be perhaps the first locally administered therapy which does appear to have a systemic impact that can hold up in phase 3. Dr. Diwakar Davar: Very, very, very exciting results. And I guess it's worthwhile pointing out that this company also has got, I think, multiple studies planned with both RP1 and cutaneous squamous cell carcinoma in a solid organ transplant patient population where single agent activity has already been reported by Dr. Migden at prior meetings, as well as a novel trial of potentially RP2 metastatic uveal melanoma. So we'll now pivot to Abstract 6014. So, 6014 is a drug by a company known as Merus. Essentially, it's a very novel agent. Merus essentially is a company that is specialized in making bicyclics and tricyclics. And these are not bicycles or tricycles, but rather drugs that essentially are bispecific antibodies. And Merus essentially has come up with petosemtamab. I think we're going to have to figure out better names for all of these drugs at some point. But petosemtamab, or MCLA-158, essentially is a bicyclic, targeting both EGFR as well as LGR-5. So EGR-5, of course, is a known oncogenic driver in multiple tumor types, squamous, including non small cell lung cancer, cutaneous squamous cell carcinoma, but also head and neck squamous cell carcinoma. And LGR-5 essentially is leucine-rich repeat-containing G-protein coupled receptor 5, but it's a receptor in cancer stem cells and certainly highly expressed in head neck squam. And MCLA-158, or petosemtamab is a IgG one bispecific with ADCC-activity because of IgG1 backbone co-targeting EGFR and LGR5. Merus had earlier results that evaluated petosemtamab monotherapy. They defined the RP2D and second- and third-line head and neck blastoma patients with a respectable response rate of 37% investigator-assessed ORR with six months median DoR, and this was published by Ezra Cohen about a year or so ago.  In this abstract, Dr. Fayette and colleagues report on the results of the MCLA-158-CL01 trial, which is a trial of pembrolizumab plus petosemtamab in one front line head and neck squamous cell population. So maybe let's start with the description of the cohort. And it is a small trial, but we'll be able, I think, to dig into a little bit about why this might be exciting. Dr. Jason Luke: Yes. So, as alluded to, it's not the biggest trial as yet, but there were 26 patients with anti PD-1 treatment naive head and neck squamous cell carcinoma. And all the patients in the study did receive, as you alluded to, pembrolizumab plus petosemtamab. Based on the label for pembrolizumab, all the patients in this study were PDL-1 positive. So that's one point that it's worth pointing out to make sure that that's understood. This is the population of patients who would be expected to benefit from pembrolizumab in the first place. Now, in the abstract, they reported out only 10 response evaluable patients, but they updated that in the actual slides of presentation at the meeting. So among 24 patients that were alluded to, 67% were described as having had a response, although some of those were yet to be confirmed responses. And when it was evaluated by PDL-1 status, there didn't seem to be a clear enrichment of response in the PD-1 positive more than 20% group, as compared to the 1-19% group. That isn't especially surprising because that was a trend that one would see, presumably with pembrolizumab alone. But overall, I think these data are pretty exciting in terms of a preliminary study. Dr. Diwakar Davar: You know, you mentioned that the objective response rate was high, almost 60-something%. The prognosis of these patients is generally poor. The OS is typically thought of as between 6-15 months. And based on KEYNOTE-048, which was led by Dr. Burtness and colleagues, the standard of care in the setting is pembrolizumab +/- platinum based chemotherapy regimens. Allowing for the fact that we only have 10 patients here, how do you think these results stack up against KEYNOTE-048? And you made a very important point earlier, which was, by definition, pembro is on label only for the CPS. So PDL-1 score, at least in head and neck squamous cell carcinoma CPS and not TPS. But in the CPS 1% or greater patient population, where pembro is on label, how do these results stack up against the KEYNOTE-048 results. Dr. Jason Luke: Right. KEYNOTE-048 is considered the seminal study that dictates frontline treatment in head and neck cancer. And before we dive into this too far, we do want to acknowledge that here we're comparing 26 patients versus a phase 3 trial. So, we're not trying to get too far ahead of ourselves, but this is just a preliminary comparison. But in KEYNOTE-048, as you alluded to, two regimens were superior to chemotherapy. One was the pembrolizumab monotherapy, as well as pembrolizumab plus chemotherapy. So again, the study overall survival, of course, was much higher, the PDL-1 positive subgroup, which is what dictated the unlabeled use of this. But response to pembro monotherapy in that population of patients is still modest. We're talking about upwards of 20-30%. So, if you compare that to, again, preliminary evidence here from this trial of only 24 patients, that response rate of 60% seems extremely high. And so even if that were to come down somewhat in a larger data series of patients, that still looks to be quite promising as a treatment regimen, that might eventually even be chemotherapy sparing for this population of patients. I think this raises a lot of eyebrows that perhaps this dual targeting approach, EGFR and LDR-5, may bring something really important to the field that evolves it. Dr. Diwakar Davar: So, what are the next steps for petosemtamab? You mentioned that the activity was interesting. Are we going to see a larger trial? Any thoughts on where things are going to go?  Dr. Jason Luke: Well, based on the phase 2 data of petosemtamab alone, even without pembrolizumab, the molecule had already been given fast track designation by FDA, which means allowing for greater communication between the drug sponsor in the FDA and designing a seminal study design. One would assume that this trial will be rapidly expanded quite greatly, perhaps to 100 or 200 patients, to try to flush out what the real response rate is in a more meaningful number of patients. But I think these data will probably also trigger the design and probably near-term evaluation or expedited acceleration of a phase III clinical trial design that would potentially validate this against the current standard of care. So, I'm pretty excited. I think we'll see a lot more about this agent in the relatively near future. Dr. Diwakar Davar: So, finally, we'll pivot to the last abstract that we're going to talk about, which is Abstract 2504. It's a relatively interesting target, CCR8 monoclonal antibody. But this is the efficacy and safety of LM-108, and LM-108 is an anti CCR8 monoclonal antibody that is being developed by LaNova Medicine. And the results that are described, actually a pool set of results of combinations of LM-108 with anti PD-1, two separate anti PD-1, in patients with gastric cancer, mostly done ex-U.S., which is interesting because of this patient population, and it's a pool result of several, 3 phase 1 and 2 studies.  LM-108 is an Fc-optimized anti CCR8 monoclonal antibody that selectively depletes tumor infiltrating Tregs. The abstract reported a pooled analysis of three phase 1, 2 trials with 3 different NCT numbers that all evaluated the efficacy of LM-108 and anti PD-1 in patients with gastric cancer. So, let's start with the description of the cohort. Maybe, Jason, you can tell us a little bit about before you start, as you describe the cohort, sort of what we know, editorially speaking, about the difficulty with which Tregs depletion has been tried and obviously failed up until now in the tumor microenvironment. Dr. Jason Luke: Right. I think that's a really interesting comment. And so, for decades, in fact, targeting regulatory T-cell to alleviate immune exclusion in the tumor microenvironment has been of interest in immuno-oncology. And in preclinical mouse models, it seems quite clear that such an approach can deliver therapeutic efficacy. However, by contrast, in human clinical trials, various different Treg depleting strategies have been attempted, and there's really little to no evidence that depleting Tregs from human tumors actually can deliver therapeutic responses. And by that we're referring to CD-25 antibodies. The drug ipilimumab, the CTLA-4 antibody, was punitively described as a Tregs depleter preclinically, but that doesn't seem to be the case in patients. And so, in that background, this is quite an eye raiser that an anti CCR8 antibody could be driving this effect. Now, before we talk about the results of this trial, I will point out, however, that given the Fc-optimization, it's entirely possible that the Tregs are being depleted by this mechanism, but that more could also be going on. Because Fc gamma RII binding by this antibody that could be nonspecific also has the potential to trigger immune responses in the tumor microenvironment, probably mediated by myeloid cells. So I think more to come on this. If this turns out to be the first meaningful Tregs depletor that leads to therapeutic efficacy, that would be very interesting. But it's also possible this drug could have multiple mechanisms.  So, having said all of that, in the clinical trial, which was a pooled analysis, like you mentioned, of LM-108 in combination with anti PD-1 of a couple different flavors, there were 48 patients treated either with LM-108, with pembrolizumab, or with toripalimab, which is another anti PD-1 antibody. On the drug combination was, generally speaking, pretty well tolerated, noting grade 3 treatment related adverse events in the range of 38%, which is somewhat expected given combination immunotherapy. We talked about nivolumab and ipilimumab before, which, of course, gives even higher rates of immune-related adverse events, with the most common toxicities being anemia, lipase elevations, rash, ALC decrease; albeit, quite manageable. Dr. Diwakar Davar: So, what about the objective response rate? Can you contextualize the efficacy? And as you do that, maybe we'll think about what you'd expect in the context of, say, gastric cancer, especially in patients who've never really had a prior checkpoint inhibitor before. What do you think about the ORR? What do you think about the relative efficacy of this combination? Dr. Jason Luke: Well, so, in the study, they described overall response rate in the 36 patients as 36% and described immediate progression for survival of about 6.5 months. And so that was among patients who were treatment naive. And in second-line patients, they actually described an even higher response rate, although it was only 11 patients, but they're at 64%. And so, I think those data look to be somewhat interesting. When I was actually scrutinizing the actual data presented, it was of some interest to note that the quality of responses seemed to be about as good on the lower dose of LM-108, so 3 milligrams per kilogram as compared to 10 milligrams per kilogram. I think there's definitely more to learn here to try to optimize the dose and to fully understand what the overall efficacy of this treatment combination would be.  I would emphasize that in this disease, I think novel treatment strategies are certainly warranted. While anti PD-1 with chemotherapy has moved the needle in terms of standard of care treatment, it's really only a minor subset of patients who derive durable long-term benefit like we normally associate with immune checkpoint blockade. I think these are preliminary data. They're very intriguing.   You alluded to earlier that this population of patients was an Asian data set, and it is well known that the efficacy of chemotherapy and immunotherapy does appear to be somewhat enhanced in Asian populations, and that goes to distributions of metastasis and tumor microenvironment effects, etc. Very difficult to try to tease any of that out in this abstract, other than to look at these data and suggest that this is pretty interesting, both from a novel therapeutic approach, we talked about the Tregs consideration, but also straight up on the efficacy because I think if these data could hold up in a larger number of patients, and particularly in a western population of patients, I think it would be very intriguing. Dr. Diwakar Davar: Certainly, ASCO 2024 had a lot of interesting data, including data from targeted agents, the LAURA trial, ADCs. But just focusing on the immune therapy subset, we certainly saw a lot of great advances in patients who were treated with neoadjuvant as well as relapse refractory disease in the context of RP1 and then a couple of newer agents such as this petosemtamab as well as LM-108. And of course, we cannot forget to highlight the extended DMFS data from the pembro vaccine study from KEYNOTE-942.  Jason, as always, thank you for taking a little bit of time out of your extremely busy schedule to come and give us insights as to how these agents are impacting the landscape. We really value your input and so thank you very much.  Dr. Jason Luke: Thank you for the opportunity. Dr. Diwakar Davar: And thank you to our listeners for your time today. You will find the links to all the abstracts that we discussed in the transcript of this episode. And finally, if you value the insights that you hear on this podcast, please take a moment to rate, review and subscribe wherever you get your podcasts. So, thank you.   Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.   Follow today's speakers:   Dr. Diwakar Davar   @diwakardavar   Dr. Jason Luke   @jasonlukemd      Follow ASCO on social media:    @ASCO on Twitter   ASCO on Facebook   ASCO on LinkedIn      Disclosures:       Dr. Diwakar Davar:     Honoraria: Merck, Tesaro, Array BioPharma, Immunocore, Instil Bio, Vedanta Biosciences    Consulting or Advisory Role: Instil Bio, Vedanta Biosciences    Consulting or Advisory Role (Immediate family member): Shionogi    Research Funding: Merck, Checkmate Pharmaceuticals, CellSight Technologies, GSK, Merck, Arvus Biosciences, Arcus Biosciences    Research Funding (Inst.): Zucero Therapeutics    Patents, Royalties, Other Intellectual Property: Application No.: 63/124,231 Title: COMPOSITIONS AND METHODS FOR TREATING CANCER Applicant: University of Pittsburgh–Of the Commonwealth System of Higher Education Inventors: Diwakar Davar Filing Date: December 11, 2020 Country: United States MCC Reference: 10504-059PV1 Your Reference: 05545; and Application No.: 63/208,719 Enteric Microbiotype Signatures of Immune-related Adverse Events and Response in Relation to Anti-PD-1 Immunotherapy       Dr. Jason Luke:    Stock and Other Ownership Interests: Actym Therapeutics, Mavu Pharmaceutical, Pyxis, Alphamab Oncology, Tempest Therapeutics, Kanaph Therapeutics, Onc.AI, Arch Oncology, Stipe, NeoTX    Consulting or Advisory Role: Bristol-Myers Squibb, Merck, EMD Serono, Novartis, 7 Hills Pharma, Janssen, Reflexion Medical, Tempest Therapeutics, Alphamab Oncology, Spring Bank, Abbvie, Astellas Pharma, Bayer, Incyte, Mersana, Partner Therapeutics, Synlogic, Eisai, Werewolf, Ribon Therapeutics, Checkmate Pharmaceuticals, CStone Pharmaceuticals, Nektar, Regeneron, Rubius, Tesaro, Xilio, Xencor, Alnylam, Crown Bioscience, Flame Biosciences, Genentech, Kadmon, KSQ Therapeutics, Immunocore, Inzen, Pfizer, Silicon Therapeutics, TRex Bio, Bright Peak, Onc.AI, STipe, Codiak Biosciences, Day One Therapeutics, Endeavor, Gilead Sciences, Hotspot Therapeutics, SERVIER, STINGthera, Synthekine    Research Funding (Inst.): Merck , Bristol-Myers Squibb, Incyte, Corvus Pharmaceuticals, Abbvie, Macrogenics, Xencor, Array BioPharma, Agios, Astellas Pharma , EMD Serono, Immatics, Kadmon, Moderna Therapeutics, Nektar, Spring bank, Trishula, KAHR Medical, Fstar, Genmab, Ikena Oncology, Numab, Replimmune, Rubius Therapeutics, Synlogic, Takeda, Tizona Therapeutics, Inc., BioNTech AG, Scholar Rock, Next Cure    Patents, Royalties, Other Intellectual Property: Serial #15/612,657 (Cancer Immunotherapy), and Serial #PCT/US18/36052 (Microbiome Biomarkers for Anti-PD-1/PD-L1 Responsiveness: Diagnostic, Prognostic and Therapeutic Uses Thereof)    Travel, Accommodations, Expenses: Bristol-Myers Squibb, Array BioPharma, EMD Serono, Janssen, Merck, Novartis, Reflexion Medical, Mersana, Pyxis, Xilio

“Talladega Nights gets a lot better after you've seen Rise of Skywalker, that's for sure” The Panel of Peril run and gun all your favourite film and video games characters in one fluid motion, before removing their VR headset in order to watch this week's film. That film is Ready Player One (Steven Spielberg, 2018), and they are joined by Kevin and Jason from KJ & A Podcast! Wade Watts (Tye Sheridan) is just like most people in the year 2045; he gets through the day any way he can before escaping to the virtual reality of the OASIS to enact his fantasies. But when the now-deceased VR creator Halliday (Mark Rylance) challenges the players to find his hidden easter egg, and gain control of the OASIS, the virtual race is on – and it will be fought to the literal death. Watch the trailer here: https://www.youtube.com/watch?v=cSp1dM2Vj48 ********PLOT SPOILER ALERT******** Nicolas Sorrento (Ben Mendelsohn) plans to find the egg for his own nefarious ends. He will monetise the OASIS, restricting access for those on the lowest incomes, thereby turning a dream playground into a corporate nightmare. Starring the likes of (friend of the pod) Batman, Chun Li, Chucky and Mecha Godzilla, RP1 is certainly a film with lots of stuff to point at when you spot it. Just what did the panel think of this week's movie, pray tell? How can they improve upon Sorrento's OASIS-hijacking plan? And who will be christened this week's most diabolical? https://twitter.com/diabolicalpod https://www.instagram.com/diabolicalpod/ https://www.facebook.com/diabolicalpod Email diabolicalpod@gmail.com

Pasar Kripto kian menggeliat di 2024 didorong momentum pengurangan pasokan baru atau halving day Bitcoin. Harga Bitcoin sudah pecah rekor, melampaui US$68.000 atau lebih dari Rp1 miliar. Antusiasme pasar di tanah air terlihat dari jumlah investor kripto per Februari 2024 yang mencapai 19 juta orang, berdasarkan data Badan Pengawas perdagangan Berjangka Komoditi (Bappebti). Jumlah ini naik dari Januari yang tercatat 18,83 juta orang. Besaran transaksinya pun melonjak dari Rp21,57 triliun pada Januari menjadi sekitar Rp50 triliun lebih. Bagi anda yang tertarik untuk berinvestasi di kripto, baiknya jangan karena FOMO, karena aset ini termasuk kategori high risk. Nah, apa saja hal-hal mendasar yang harus diketahui sebelum invest di kripto? Bagaimana perencanaan keuangannya? Strategi seperti apa yang cocok diterapkan agar investasi kripto aman dan cuan? Kita bahas topik seru ini di Ruang Publik KBR bersama Financial Market Specialist, Lucky Bayu Purnomo dan Rieka Handayani, VP PR & Marketing Tokocyrpto. *Kami ingin mendengar saran dan komentar kamu terkait podcast yang baru saja kamu simak, melalui surel ke podcast@kbrprime.id

*Apologies for the poor audio quality on Taylor's mic as we experienced some technical difficulties during recording* On this episode, Kyle and Taylor are joined by Enrico to discuss relief pitchers. Topics discussed include whether Emmanuel Clase should be RP1 in dynasty, what to do with Felix Bautista, and why Evan Phillips and Clay Holmes are criminally underrated. Thank you for listening and be sure to follow us on Twitter/X at (⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠https://twitter.com/GreatDebateTC⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠) and (⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠https://twitter.com/_sonny_50⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠) where the ADP will be posted if you want to follow along. We are excited to now be part of Prospects Live! Be sure to follow the account on Twitter/X (⁠⁠⁠https://twitter.com/ProspectsLive⁠⁠⁠). Consider subscribing to the Patreon (⁠⁠⁠https://www.patreon.com/prospectslive⁠⁠⁠), starting at just $5 a month, to get access to amazing tools and content such as: PLive+ Peak Projections Top 1000 Dynasty Rankings (with Auction Values and League Analyzer) Top 500 Prospect Rankings Trade Analyzer Top 30 team scouting reports with added fantasy context Daily sheets (including for Spring Training, AFL, and LIDOM) Private discord channels for tier 70 and up. Additional written and audio content, including more from us! Also check out the Fantasy Baseball Discord to interact with us and many other great fantasy/dynasty/prospect minds (⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠http://discord.gg/fantasybaseball)⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠. Finally please rate and review the podcast if you have not done so already as that would really help us out.

Dalam rangka perayaan ulang tahun ke-128, BRI mengadakan BRImo FSTVL dan berkolaborasi dengan Swarna Land yang menampilkan konser musik Nadin Amizah bersama The Secret, Happy Soda, dan Brilian Band pada Sabtu 09 Desember 2023. Tidak hanya, para pengguna BRImo bisa mendapatkan doorprize dari BRI. Pengunjung hanya perlu scan QRIS yang telah disediakan saat entry gate menggunakan BRImo sebesar Rp1 dan dapatkan kupon doorprize yang akan diundi untuk mendapatkan hadiah selama event berlangsung. Pengunjung juga bisa mendapatkan kupon belanja dengan menukarkan 2 botol plastik di booth BRI. Konser Nadin Amizah ini dilaksanakan di pool Pangeran Beach Hotel Padang.

Headline News MetroTV Edisi 2273 kali ini membahas harga emas 24 karat cetakan PT Aneka Tambang Tbk (Antam) turun hari ini. Mengacu laman Logam Mulia, Selasa, 31 Oktober 2023 harga emas Antam turun Rp4.000 dari Rp1,135 juta menjadi Rp1,131 juta untuk ukuran satu gram.

James Adams and Liam Fraser of the Raspberry Pi hardware team once again join Chris to talk about the RP1 custom silicon on the Raspberry Pi 5

This week's Electromaker Show is now available on YouTube and everywhere you get your podcasts! Welcome to the Electromaker Show episode 124! This week our product of the week is the Arduino Nano ESP32 - yes, everyone's favorite SoC on the world's most loved development board. We also find out more about the RP1 from Raspberry Pi, see an amazing new rotary encoder devboard from M5Stack, and return to Crowd Supply for Funding Website Things! Tune in for the latest maker, tech, DIY, IoT, embedded, and crowdfunding news stories from the week.   Watch the show! We publish a new show every week. Subscribe here: https://www.youtube.com/channel/UCiMO2NHYWNiVTzyGsPYn4DA?sub_confirmation=1 We stock the latest products from Adafruit, Seeed Studio, Pimoroni, Sparkfun, and many more! Browse our shop: https://www.electromaker.io/shop Join us on Discord! https://discord.com/invite/w8d7mkCkxj​ Follow us on Twitter: https://twitter.com/ElectromakerIO Like us on Facebook: https://www.facebook.com/electromaker.io/ Follow us on Instagram: https://www.instagram.com/electromaker_io/ Featured in this show: Product of the Week: Arduino Nano ESP32 More Pi 5 development goodies: RP1 ESP32 based Gesture remote MQTT Anywhere Giveaway Winner announced! Crowd Supply Lightning Round: PolyKybd AI in a box: Offline LLM assistant HaxaPhone Update! Mini robot Mic Swarms: M5 Stack rotary encoder screen with ESP32

The Raspberry Pi 5 is the latest version of one of the world's most popular computers. It was just announced on Thursday and will be released on October 23rd. The new model comes in two versions, a 4GB and an 8GB model, priced at $60 and $80 respectively. Compared to the previous Raspberry Pi 4 models, these prices are only $5 more.Raspberry Pi 5 is faster and improvedOne of the main improvements of the Raspberry Pi 5 is its faster processing power. It features a new Broadcom system on a chip (SOC) with a quad-core CPU running at 2.4GHz and a quad-core GPU. The previous model had a CPU running at 1.8GHz and a GPU with lower clock speed. The new SOC allows for overclocking up to 3GHz, providing even better performance.The GPU of the Raspberry Pi 5 is a video core seven GPU with a stock speed of 800MHz, compared to 500MHz on the previous model. Although overclocking the GPU did not result in significant graphics improvements, the overall performance of the device is noticeably faster for various tasks.Another notable improvement is the inclusion of the RP1 chip, designed by Raspberry Pi, which controls the IO for the USB3 ports, USB2 ports, and Ethernet port. This allows for higher throughput, resulting in faster read and write speeds for USB devices. The Ethernet port remains a gigabit port, providing similar speeds to the previous model. The Wi-Fi card, however, has a faster interconnect to the CPU, resulting in double or more than double the speed of the Raspberry Pi 4 under good conditions.The Raspberry Pi 5 does not come with a fan, but it is recommended to use one to prevent overheating. Without a fan, the device can reach temperatures up to 80 degrees Celsius, which is the throttle point. The official fan, specifically designed for this layout, is available for around $6. It can be easily mounted on the device using the dedicated mounting holes and four-pin header.Overall, the Raspberry Pi 5 offers significant improvements in processing power, graphics performance, and IO throughput compared to its predecessor. It is a highly anticipated computing device that provides faster and improved capabilities for various applications.New Raspberry Pi features power buttonOne of the standout features of the new Raspberry Pi 5 is the addition of a power button, which is a first for the Raspberry Pi line. This power button allows users to easily turn the device on and off without having to unplug it from the power source. However, it is important to note that the power button is not a hard cutoff switch, but rather a soft momentary button that initiates shutdown when pressed.The addition of a power button may not seem like a significant feature, but it offers several benefits. Firstly, it eliminates the need to unplug the device to turn it off, which can be inconvenient and potentially lead to the corruption of the SD card. With the power button, users can safely shut down the Raspberry Pi without the risk of data loss or corruption.Additionally, the power button allows for easier and quicker boot-up times. When the Raspberry Pi is plugged into the power source, it automatically boots up, eliminating the need to manually turn it on. This can be particularly useful in situations where the device needs to be constantly powered on and off, such as in a server setup.Furthermore, the power button is programmable, meaning that users can customize its functionality to suit their needs. Currently, pressing the power button brings up the shutdown menu on the screen. However, it is possible to program it to perform other actions, such as initiating a specific command or launching a particular application. This programmability adds an extra layer of versatility to the Raspberry Pi 5 and allows users to tailor its functionality to their specific requirements.

Prejuicios por el fondo de tus videollamadas / Intel Irlanda arranca los 4 nm / Raspberry Pi 5 por sorpresa / Redada de Nvidia en Francia / Diseña tu propia galaxia Patrocinador: Por fin llega a los cines The Creator, una de las películas de ciencia ficción más esperada. Se estrena el 29 de septiembre y que no te puedes perder por nada del mundo. Dirigida por Gareth Edwards (su primera película tras Rogue One), estoy seguro que The Creator será un clásico instantáneo. — ¿Has visto ya el trailer? Prejuicios por el fondo de tus videollamadas / Intel Irlanda arranca los 4 nm / Raspberry Pi 5 por sorpresa / Redada de Nvidia en Francia / Diseña tu propia galaxia

Pemerintah dengan DPR RI menyepakati target penerimaan pajak tahun 2024 sebesar Rp1.988,8 triliun.

Drs Sapna P. Patel and Kim A. Margolin sift through the data from studies presented at recent conferences, including the KEYNOTE-942 and RP1 IGNYTE studies. Relevant disclosures can be found with the episode show notes on Medscape (https://www.medscape.com/viewarticle/989036). The topics and discussions are planned, produced, and reviewed independently of advertisers. This podcast is intended only for US healthcare professionals. Resources An Efficacy Study of Adjuvant Treatment With the Personalized Cancer Vaccine mRNA-4157 and Pembrolizumab in Participants With High-Risk Melanoma (KEYNOTE-942) https://classic.clinicaltrials.gov/ct2/show/NCT03897881?term=Keynote-942&draw=2&rank=1 A Personalized Cancer Vaccine, mRNA-4157, Combined With Pembrolizumab Versus Pembrolizumab in Patients With Resected High-Risk Melanoma: Efficacy and Safety Results From the Randomized, Open-Label Phase 2 mRNA-4157-P201/Keynote-942 Trial https://www.abstractsonline.com/pp8/#!/10828/presentation/10243 Distant Metastasis-Free Survival Results From the Randomized, Phase 2 mRNA-4157-P201/KEYNOTE-942 Trial https://ascopubs.org/doi/abs/10.1200/JCO.2023.41.17_suppl.LBA9503 Neoadjuvant-Adjuvant or Adjuvant-Only Pembrolizumab in Advanced Melanoma https://pubmed.ncbi.nlm.nih.gov/36856617/ Pembrolizumab Versus Placebo as Adjuvant Therapy in Stage IIB or IIC Melanoma: Final Analysis of Distant Metastasis-Free Survival in the Phase 3 KEYNOTE-716 Study https://ascopubs.org/doi/abs/10.1200/JCO.2023.41.17_suppl.LBA9505 Study of RP1 Monotherapy and RP1 in Combination With Nivolumab (IGNYTE) https://www.clinicaltrials.gov/study/NCT03767348?term=Study%20of%20RP1%20Monotherapy%20and%20RP1%20in%20Combination%20With%20Nivolumab%20(IGNYTE)&rank=1 Talimogene Laherparepvec (T-VEC): An Intralesional Cancer Immunotherapy for Advanced Melanoma https://pubmed.ncbi.nlm.nih.gov/33803762/ Randomized, Double-blind, Placebo-Controlled, Global Phase III Trial of Talimogene Laherparepvec Combined With Pembrolizumab for Advanced Melanoma https://pubmed.ncbi.nlm.nih.gov/35998300/ Phase I Study of Fianlimab, a Human Lymphocyte Activation Gene-3 (LAG-3) Monoclonal Antibody, in Combination With Cemiplimab in Advanced Melanoma https://oncologypro.esmo.org/meeting-resources/esmo-congress/phase-i-study-of-fianlimab-a-human-lymphocyte-activation-gene-3-lag-3-monoclonal-antibody-in-combination-with-cemiplimab-in-advanced-melanoma Significant Durable Response With Fianlimab (Anti-LAG-3) and Cemiplimab (Anti-PD-1) in Advanced Melanoma: Post Adjuvant PD-1 Analysis https://ascopubs.org/doi/abs/10.1200/JCO.2023.41.16_suppl.9501?af=R Relatlimab and Nivolumab Versus Nivolumab in Untreated Advanced Melanoma https://pubmed.ncbi.nlm.nih.gov/34986285/ BRAF and MEK Inhibition in Melanoma https://pubmed.ncbi.nlm.nih.gov/25648338/ Anti-PD-1 and Anti-CTLA-4 Therapies in Cancer: Mechanisms of Action, Efficacy, and Limitations https://pubmed.ncbi.nlm.nih.gov/29644214/ Society for Immunotherapy of Cancer (SITC) Consensus Definitions for Resistance to Combinations of Immune Checkpoint Inhibitors https://pubmed.ncbi.nlm.nih.gov/36918224/ RECIST 1.1 – Update and Clarification: From the RECIST Committee https://pubmed.ncbi.nlm.nih.gov/27189322/ Histopathological Features of Complete Pathological Response Predict Recurrence-Free Survival Following Neoadjuvant Targeted Therapy for Metastatic Melanoma https://pubmed.ncbi.nlm.nih.gov/32739408/

Melepas Jerat Utang Ribawi dengan Solusi Hakiki Oleh. Trisna Abdillah(Kontributor NarasiPost.Com) Voice Over Talent: Dewi Nasjag NarasiPost.Com-Jelang tahun pemilu 2024, lonjakan jumlah utang pemerintah kembali menjadi polemik. Mantan Wakil Presiden RI Jusuf Kalla (JK) menyebut jumlah utang melonjak tajam di masa pemerintahan Presiden Joko Widodo (Jokowi). JK mengatakan dalam setahun negara membayar bunga dan utang lebih dari Rp1.000 T terbesar dalam sejarah Indonesia sejak kemerdekaan. Jika hal ini berlangsung terus menerus, ia menilai utang pemerintah yang tinggi akan menjadi bom waktu dan membebani pemerintah berikutnya, sebab beban utang dan bunga berimbas semakin menyempitnya ruang fiskal APBN. (Kompas.com, 5/6/2023) Menteri Keuangan (Kemenkeu) Sri Mulyani tidak menepis ataupun mengiyakan keterangan JK. Ia hanya menegaskan bahwa utang pemerintah masih di batas aman dan bisa ditangani oleh negara. Naskah selengkapnya: https://narasipost.com/2023/06/08/melepas-jerat-utang-ribawi-dengan-solusi-hakiki/opini/ Terimakasih buat kalian yang sudah mendengarkan podcast ini, Follow us on: instagram: http://instagram.com/narasipost Facebook: https://www.facebook.com/narasi.post.9 Fanpage: Https://www.facebook.com/pg/narasipostmedia/posts/ Twitter: Http://twitter.com/narasipost

Like father like son, Rafael Alun-Mario Dandy, Bapak-anak kompak pakai baju tahanan. Rafael Alun tersangka korupsi sedangkan anaknya Mario Dandy tersangka penganiayaan. Menpora baru kepala BNPT juga baru. Setelah resmi dilantik presiden Jokowi, Dito Ariotedjo sebagai Menpora tentu punya PR besar. Begitu juga dengan Komjen Ryko Amelza yang kini bertugas sebagai kepala BNPT. Selamat bekerja bapak-bapak. Pemerintah Italia menerapkan kebijakan denda sebesar €100.000 atau sekitar Rp1,6 miliar bagi warganya yang pakai bahasa Inggris dan bahasa asing lainnya dalam acara resmi.

I got a demo of RP1's single shard with 4000 users in mid-July, and then chatted with 3 team members in August to unpack their journey towards creating a scalable network architecture for the Metaverse. Their demo was built on WebXR, but it could be used on other game engines as well. There are real limitations on the client-side and VR hardware with how many of those 4000 users can been rendered within a close proximity, but having a single instance with hundreds or thousands of people could start to open up new use cases for cultivating virtual spaces that recreate some of the social dynamics of tech conferences, large-scale concerts, or perhaps persistant Burning Man playa communities that focus on serendipitious collisions and real-time hangouts. I unpack RP1's design process and potential implications of large-scale shards for the Metaverse with CEO Sean Mann, Chief Architect Dean Abramson, and Chief Client Architect Yin-Chien Yeap (aka Yinch).

In this episode we speak to Raul about his recent RP1 release with The Detent Escapement. His time at Parmigiani Fleurier and the process of creating a watch, from conception to production. 

"Aku melihat bahwa tidak ada yang lebih baik bagi manusia dari pada bergembira dalam pekerjaannya, sebab itu adalah bahagiannya." (Pengkhotbah 3:22a) Renungan: Seorang pemuda yang sedang lapar pergi ke sebuah warung di pinggiran jalan. Saat ia sedang makan, datanglah seorang anak kecil penjual kue menawarkan kue kepadanya, "Pak, mau beli kue?" Dengan ramah pemuda itu menjawab, "Tidak, saya sedang makan." Anak kecil tersebut tidak putus asa ketika tawaran pertamanya ditolak. Ia menawarkan lagi kue setelah pemuda itu selesai makan. Sang pemuda menjadi risih untuk menolak. Kemudian ia mengeluarkan uang Rp1.500,- dan memberikannya sebagai sedekah saja. Anak kecil itu lalu mengambil uang pemberian sang pemuda dan memberikannya kepada pengemis. Pemuda tadi bingung dan bertanya, "Mengapa kamu memberikan uang itu kepada pengemis?" Anak kecil penjual kue itu tersenyum lugu dan menjawab, "Saya sudah berjanji pada ibu saya untuk menjual kue ini, bukan untuk menjadi pengemis. Dan saya akan bangga pulang ke rumah bertemu ibu jika kue buatan Ibu terjual habis." Pemuda tersebut merasa kagum dengan kata-kata anak kecil itu dan akhirnya ia memborong semua kue yang dijual anak kecil tersebut. Ia melakukannya bukan karena kasihan tetapi karena prinsip yang dimilikinya. Bagaimana dengan kita, sudahkah kita memunyai cara pandang yang benar tentang profesi ataupun pekerjaan kita atau apakah kita hanya beranggapan bahwa bekerja hanyalah untuk memperoleh uang? Bila cara pandang dan sikap kita terhadap pekerjaan hanya untuk memeroleh uang, maka kita akan mudah bosan, menghalalkan segala cara dan tidak menghargai orang lain maupun pekerjaan kita. Namun bila kita menganggap bahwa pekerjaan kita adalah sebuah kehormatan dan anugerah yang diberikan oleh Tuhan untuk menjadi berkat bagi orang lain, maka kita akan memberikan yang terbaik dan bekerja dengan sepenuh hati. Jadi, apapun jenis pekerjaan yang kita lakukan saat ini, entah itu pekerjaan kecil ataupun pekerjaan besar, kerjakanlah dengan sepenuh hati dan kehormatan, karena orang yang bekerja tidak hanya untuk uang, justru akan dikejar-kejar oleh berkat dari Tuhan. Tuhan Yesus memberkati. Doa: Tuhan Yesus, terima kasih untuk pekerjaan yang saat ini Kau percayakan padaku. Bantulah aku untuk melakukannya dengan baik, sehingga apa yang kukerjakan pada akhirnya menjadi berkat bukan hanya untuk diriku saja, tetapi juga untuk banyak orang dan untuk kemuliaan nama-Mu. Amin. (Dod).

Ghozali mengguncang Indonesia ketika selfienya yang berbentuk NFTs (non-fungible tokens) dihargai Rp1,5 miliar. Dalam konteks lebih besar, dunia kini tengah mengalami tren NFTs dan cryptocurrency yang popularitasnya menanjak. Peran negara dalam sistem berbasis blockchain tersebut pun dipertanyakan. Apa untung-rugi sistem ini dari kacamata sosial-politik? Bagaimana tata kelola ruang siber (cyberspace) di dunia internasional? Apakah negara tidak lagi relevan? Simak analisis selengkapnya di Podcast Bebas Aktif! Instagram: @kontekstualcom Twitter: @kontekstualcom YouTube: Kontekstual Kunjungi kontekstual.com untuk berita HI paling aktual!

The Dow Family and The Dow Realty Company! Rich in tradition and Family Values. If you have ever met Jeff Dow, you would remember him. He is an extremely nice person, with a great family history, and certainly a giver,both in his profession and his community.  He continues the values and integrity of his family.  His business was built on honesty and hard work.  Dow Realty has a wonderful reputation dating back to 1983 when Jeff's dad, Robert E Dow founded the company it. Immediately, Bob's company had prominence in New Haven County and a great reputation.   He was well versed in the commercial real estate profession and had a great professional reputation. .Jeff Dow started with Dow Realty in 2008, continuing the great tradition of   Dow Realty.    In this video, Jeff shares with us, how the commercial real estate market works, what to look for when buying and , what to avoid. In this educational video Jeff discusses the in-depth analytics that areis needed when comparing property and evaluating as to whether it will create the ROI for an investor.[RP1]  can receive. from their investment in the property. Commercial real estate, as we learn from Jeff, is not like buying a home. If you are not careful, what seems like a great investment could end up being a nightmare. Jeff is a seasoned veteran and takes his education of his profession seriously. Jeff is a designee of the CCIM institute, a real estate designation held by only 6% of commercial real estate practitioners nationwide. You can reach Jeff at: Dow Realty Co. 943 Grand Ave. New Haven, CT 06511Cell: 203 –824-7760203-776-000Fax: 203-565-7707www.dowrealty.com

Thor, Stubbs, and Axryn host an RH community night AMA with a slew of community guests! This episode was almost lost as Stubbs didn't get his audio recorded, luckily he was crazy enough to re-record his parts from scratch. What ensues is pure madness, with a dash of reveals, GOTM, GOTY news, and even a sing-a-long! Lets go!Thanks to our patrons!Join our Patreon at https://patreon.com/RetroHandheldsJoin our Discord at https://discord.gg/RetroHandheldsBRB Theme by Choosh 

YouTuber JimRPG joins the gang on a wild ride through the handheld world, their favorite black friday deals, and many other topics we won't spoil for you with this silly summary. Happy turkey times, everyone!JimRPG on the internet: YouTube: https://youtube.com/c/JimRPGTwitter: @JimRPGDiscord: https://discord.gg/gXs9JhUtrkYouTube2: https://youtube.com/channel/UCWgiqwQCTOhXdq1JbEfJ63ATheme song by ChooshOur Discord: https://discord.gg/RetroHandhelds

Bill interviewed a few of the exhibitors at the 2021 SEMA show.Hawk Performance Brakes:Taylor Allen shares more information about Hawk and announces the new endurance racing brake pad.Hawk's InstagramEBC Brakes:Candice and Steve share more about EBC brakes.  We learn RP1 & RPX pads with floating discs and they tease us about a new release that will be announced at PRI. EBC Brakes InstagramRacingJunk.com:Ian Downey tells us more about RacingJunk.com services  and reminds us that it's a free site.  Buying or selling a race car, trailer, to rig has never been easier!Racing Junk InstagramOhlins:Brian Fowler tells us more about the products that Ohlins offers and reminds us that Ohlins was selected as the damper provider for  Next Gen NASCAR car.  He also shares a few new product launches.Ohlins Instagram NRG Innovations:Jason the VP at NRG Innovations talks about their affordable product lines for your daily driver and your track car.  They are releasing a new line of reclining seats and designer steering wheels.NRG InstagramBig Kids Garage:James Packer tells us more about his new project, Big Kids Garage.  He's a NASA racer and has a long history in motorsports.Big Kids Garage InstagramEssex Racing:Jack from Essex Racing which is the exclusive AP distributor in America talks about AP Racing's products which includes brake components and clutches.  He also discusses the selection of AP to part of the Next Gen NASCAR car.Essex Racing InstagramG-Force Racing Gear:Craig Robinson tells us all about what G-Force Racing has to offer and highlights their new helmet. We learn that a new suit, glove and  shoe line is coming out next year.  For this year there is the Super Nova T800, full carbon fiber helmet.G-Force Instagram

Nick and Single White Medusa talkCheck out Nick's book CTRL ALT Revolt!Christopher DiNote5.0 out of 5 stars This series is what Ready Player One could have been..Reviewed in the United States on October 31, 2019Verified PurchaseIn other words, actually great. Nick Cole pulls off an incredible synthesis of pop culture, Hollyweird (likely from personal experience), California (likely also from personal experience), big tech, action, satire (sometimes just a little bit too on the nose, but his targets are well deserving of some mockery, they've gotten off too easy in the past), gamer culture (more 1990s than 80s, but lots of retro goodies for those of us of a certain age), Star Trek, and the Terminator.Speaking of those two, this is very much a full-blown Star Trek novel, in the same way that Galaxy Quest was a Star Trek movie - the best one), and a Terminator story (the best since Alex Ross had his crack at it years and years ago). My one quibble is the corporate rah-rah at the end which I think gives them a little too much credit, but it does set up the sequels very, very well with a bit of irony, whether that is intentional or not.I was also struck that there's more than a little bit of Jerry Pournelle's CoDominion in there too, especially the early days stories captured in High Justice. Cole also seems to have three permanent features in any of his books that makes me wonder if there isn't a "Dark Tower" -esque metastructure at work: zombies, Terminators, and the apocalypse. Over and over again. I can't figure out if he's writing the world's greatest "fix" fanfic series of all time, or if something deeper at play.Synthesized together like this, it attains a far greater depth and perspective, sans nihilism and fatalism, than RP1. This is a public episode. If you'd like to discuss this with other subscribers or get access to bonus episodes, visit nickcole.substack.com/subscribe