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Dr Reckamp discusses the definition of pragmatic clinical trials and ways that clinical trial investigators can make their research more pragmatic.

Year in Review: Clinical Investigator Perspectives on the Most Relevant New Data Sets and Advances in Targeted Therapy for Non-Small Cell Lung Cancer | Faculty Presentation 1: Management of Non-Small Cell Lung Cancer (NSCLC) with an EGFR Mutation — Karen Reckamp, MD, MS CME information and select publications

In this LinkedIn Live, Erica Reckamp and I delve into the reputational management of job seekers who have come under fire in their previous employment. Erica advises on how you can position yourself to ensure you are still viable within your industry or undergo a career pivot to land your next role.

Host Dr. John Sweetenham and guests Dr. Karen Reckamp and Dr. Harpreet Singh discuss the S2302 Pragmatica-Lung trial, a streamlined, real-world clinical trial that is poised to simplify and transform the entire clinical trials model as we know it. TRANSCRIPT Dr. John Sweetenham: Hello, I'm Dr. John Sweetenham, the associate director for cancer network clinical affairs at UT Southwestern's Harold C. Simmons Comprehensive Cancer Center and host of the ASCO Daily News Podcast.  Today, we are going to be discussing a streamlined, real-world clinical trial from the Southwest Oncology Group (SWOG), which is S2302, also known as the Pragmatica-Lung trial. This study is poised to simplify and transform the entire clinical trials model as we know it. Joining me for this discussion is the trial's lead investigator, Dr. Karen Reckamp. Dr. Reckamp is a clinical professor, director of the Division of Medical Oncology, and associate director for clinical research at Cedars-Sinai Samuel Oschin Cancer Center. I'm also delighted to welcome Dr. Harpreet Singh, the director of 1 of 3 divisions of oncology at the U.S. Food and Drug Administration. She will discuss the FDA's views on streamlining clinical trials to reach more representative groups of patients and will also more broadly address some of the key questions that regulators consider when deciding on whether real-world data can substitute for randomized controlled trials. Our full disclosures are available in the transcript of this episode, and disclosures relating to all episodes of the podcast are available on our transcripts at asco.org/DNpod. Dr. Reckamp and Dr. Singh, it's a great pleasure to have you on the podcast today. Dr. Karen Reckamp: Thank you for having us. Dr. John Sweetenham: Dr. Reckamp, I'm going to start with you if I may and ask if you could give us some background on S2302, the Pragmatica-Lung trial for non-small cell lung cancer. Dr. Karen Reckamp: Sure. The Pragmatica-Lung trial really started with the sub-study from Lung-MAP, which was called S1800A, and it was a randomized phase 2 trial that evaluated pembrolizumab and ramucirumab versus standard of care for patients who had previously received chemotherapy and immunotherapy with advanced non-small cell lung cancer and had had disease progression. And in this phase 2 trial, we found that there was an improvement in overall survival with a hazard ratio of 0.69% and survival of 14.5 months for pembrolizumab and ramucirumab, and 11.6 months for standard of care. And with that, we had again a randomized phase 2 trial, but the study was small. And so, trying to think about how to move this to the next level to get phase 3 data, we started thinking about how to do this in a way that would reduce the timelines and potentially move this treatment to patients more quickly than standard registrational, randomized phase 3 trials. And that's kind of where S2302 and Pragmatica-Lung started. Dr. John Sweetenham: So, can you tell us in a little more detail how the dramatically streamlined pragmatic design of this trial is going to hopefully simplify trial design and trial conduct in the future beyond non-small cell lung cancer?  Dr. Karen Reckamp: I think the important piece of this—and we have Dr. Singh here to speak to the FDA part—but this has been a partnership with the FDA and CTEP [NCI's Cancer Therapy Evaluation Program]. Really, our goal was to try and find a way to run trials in a more streamlined way. One of our colleagues at CTEP during this process said, “If this is not making you uncomfortable, then you're not doing it right.” So, the first thing we did was kind of lean into the discomfort because for those of us who have been writing trials and putting trials together for the last 20-plus years, this is dramatically different. And we're really looking at one question, and that is overall survival. We're trying to validate the overall survival we saw in S1800A. And with that, we stripped away all the unnecessary data collection that comes along with other types of registrational issues that come with randomized phase 3 trials. And then, we also looked at patient burden and really opened it up. So, again, pragmatically, making this practical, allowing investigators to be empowered to treat patients how they normally would in their own practice. And so, moving forward, again, for types of trials where we have drugs whose toxicity profiles are well known, they're used in practice but using novel combinations for a subset of patients who have limited treatment options available, this could really change the paradigm moving forward for these types of trials in multiple diseases. Dr. John Sweetenham: Yeah, thanks. And in addition to simplifying the trial design, obviously, one of the goals here is to have a study population which is more representative of the patients who are seen typically in community practice. Hopefully, we'll overcome some of the known disparities that we see in clinical trial accrual. Could you speak just a little bit to how the study design and the organization of the study helps to achieve that? Dr. Karen Reckamp: So, I think it's on several levels, but we are looking to allow this to be more generalizable and allow a more diverse population into this study. First, by again stripping down the eligibility criteria to only the absolute essential criteria for understanding our scientific question. And so, we don't require imaging studies to be uploaded or presented. If the patient has progression, it's based on the investigator's opinion. And so, we don't need to be searching for outside scans or things like that. We don't have tissue requirements, and we don't even actually have lab requirements. If this is a patient, you would treat your standard of care practice with the standard of care regimens; those are the labs that you do. So, it's all based on standard of care. So, by doing this based on standard of care, it really allows almost any patient to enroll. And then we have outreach. We have our DEI group and our community practices very well engaged to make sure that we have broad reach. Having this open through NCTN [NCI's National Clinical Trials Network] will make sure that we get this to multiple practices in far-reaching parts across the United States. Dr. John Sweetenham: Yeah, I think that's excellent. And you've already alluded to the fact that the data collection requirements for the study are going to be kind of pared down to the absolute minimum and that's going to include, I believe, toxicity reporting as well. So, can you comment a little bit on that and, specifically, what your plans are for reporting toxicity in this trial? Dr. Karen Reckamp: Yes, you're correct. This is significantly pared down from what we're used to doing. And so, most clinical trial offices are struggling with staffing and making sure that their patients have enough staff and that they have enough staff to get patients onto trials efficiently, and then getting the data in is always a challenge for sites. So, we have really, again, working with our partners, working with the FDA, and with CTEP, we have minimized what we are going to collect on patients. So, we're collecting survival and vital status on patients. We are collecting the background standard information that we collect on kind of prior therapies, and we are collecting only unexpected grade 3 and higher adverse events. And so, thinking about these drugs—ramucirumab and pembrolizumab—we know how these drugs work, we know the toxicity profile, we're using them in combinations and single agents in multiple tumor types. And so, thinking about most of the immune-related adverse events wouldn't even be reportable because they're expected. And so, a large number of data that is normally collected would not be collected here. And, as noted, we don't collect scans, we don't collect labs, we're not collecting con-meds, start and stop dates. A lot of that burden of data collection, but also data auditing and queries, goes away. It should be a significantly easier trial to perform by sites.  Dr. John Sweetenham: And can you just update us on the status of the trial right now? Dr. Karen Reckamp: We're in the process of pre-activation, and so, if you're an NCTN site, you can actually go in and do some pre-training and take a look at the draft protocol. And we are anticipating approval sometime in early March. Dr. John Sweetenham: Great. Congratulations on getting this trial launched and underway because I know that the word “groundbreaking” is used a lot, but I think that, obviously, if this trial proves to be the success that it looks like it will be, then it's going to have, I think, major implications for study design in the future. And that's going to lead me to ask a couple of questions to Dr. Singh. And the first one of those is the FDA's decision to consider data from a simplified pragmatic trial design like this, which uses more limited clinical information, is really kind of almost revolutionary. And could you comment a little on this from the FDA perspective and how you think it's going to influence the future of clinical trials and the future of cross-trials? Dr. Harpreet Singh: Well, thanks so much for the question, and thanks for having me. I want to push back on that just a little bit because I think, for what it's worth, the FDA has been advocating for trial efficiencies in oncology for many years. And, of course, as you know, our current commissioner, Dr. Robert Califf, is very vested in this concept. And certainly, the idea of pragmatic trial has been there in the field of cardiology for some time.  In terms of this trial, in particular, in coming to oncology, I do think actually putting pen to paper and drafting the protocol, which we did really in cohesion with SWOG and many calls with Karen and others who were a part of this, that collaborative piece, I think, is groundbreaking because what we saw here was a great deal of discomfort, actually around everything that we were stripping down. We sensed a lot of discomfort in terms of including various, like you mentioned, safety issues, safety reporting not being perhaps as rigorous as we're accustomed to seeing at the FDA. And certainly, investigators are accustomed to collecting other endpoints besides overall survival, like time to progression, but the real-world version of that, or time to next therapy. And so, one very difficult lesson that I've had to learn, and we've had to learn, is that you have to really learn to say no to some very interesting trial design elements that are not essential to the big question here, which is, does this combination regimen offer an improvement in survival over the control? So, while I do think the actual organizational and structural piece of this, now that it's actually stood up, is groundbreaking, I think that the idea of pragmatic trials and incorporating clinical care into the idea of answering a clinical question as opposed to the traditional randomized clinical trial is a concept that's been around. I'm just thrilled to see it actually occur in this very, I think, ideal setting for patients with lung cancer. Dr. John Sweetenham: Yeah, absolutely. I want to broaden the scope of what we're discussing here just a little bit, perhaps to talk a little more about the “real world” and “real-world data.” More real-world data is being considered in regulatory decision-making. And one of the questions I have, again, from an FDA perspective, is that everyone still, I think, regards randomized controlled trials as the gold standard for evaluating efficacy if not effectiveness, of various interventions. What are the key questions that you consider when deciding whether any kind of real-world data analysis is a good substitute for a randomized controlled trial?  Dr. Harpreet Singh: Well, thank you for the question about how FDA considers real-world data when we consider this to be appropriate. There are many nuances to this. So, first of all, what is real-world data? And there's actually a distinction between real-world data, which is just simply a source used in observational studies traditionally. But real-world data is not specifically a trial design; it's just data. Whereas real-world evidence, which is evaluating the benefits and risks which are derived from real-world data, may come from things like electronic health records. It's not either-or. So, for example, in a pragmatic trial, you could use a blended approach where you have some components of real-world data or real-world practice, which we may consider kind of part of real-world data, but while retaining some elements of randomized control trials. So, I think when FDA considers real-world evidence, so I'll say that instead of data, it usually would be a source like a very high-quality registry or data obtained through a very well-designed observational study. And this would be in settings of perhaps super rare diseases in which randomization is either not feasible or, in some cases, where you may have preliminary data which suggests that randomization is not ethical. But we agree with the general idea that the gold standard is randomization.  And that's what I love about this pragmatic trial, is that you are retaining the benefit of randomization while bringing pragmatic elements in, bringing the trial to patients and really incorporating clinical practice into the trial, as opposed to the reverse, where you're having patients enrolled on a traditional trial where the visits are outside of routine. Dr. John Sweetenham: Thanks for drawing that distinction between real-world evidence and real-world data because I think the two expressions are sometimes used a little carelessly, as maybe I just did. But certainly, one of the things that I've observed over the last several years since we started to incorporate real-world data or real-world evidence into our kind of oncology lexicon is that real-world data has been used in a fairly relaxed, let's say, way and certainly any relatively small series which has been registry based or retrospective, there's been a tendency to use this term called real-world data, which personally, I've certainly seen applied to patients who are undergoing very intensive therapies such as CAR T. And certainly, when I look at the patient characteristics in those elements of so-called real-world data, it's a long way from the real world that I'm familiar with in my own practice. And so, I do think that the term has been used very loosely. And your point about real-world evidence is an important one, I think. People are still questioning whether real-world evidence in oncology is truly valid. And I think to some extent, you've already answered that question.  Do you think that there are mistakes and pitfalls that investigators can avoid when they're looking at real-world evidence? Dr. Karen Reckamp: Sure. I mean, I think the first point of clarification is, are we looking at this evidence to support use of an oncology drug in clinical practice, or are you an investigator working to bring real-world evidence to the FDA for drug approval? But either way, no matter what scenario you're in, I think the first question you must ask yourself is, is this data fit for purpose? And what does that actually mean, ‘fit for purpose'? And I think it goes to things like, are the patients well-matched? So, there's this very complex process, but the concept is not complex of propensity score matching, which our statisticians do for us beautifully. But this idea of are the patients in this data set that you're looking at, this is just a collection of data, right? How relevant is it to the patient in front of you? Is there some sort of matching that's going on in terms of patient characteristic?  After that, you have to ask yourself about this kind of array of epidemiologic biases that are inherent in non-randomized comparisons. Like, is this contemporaneous data? So, if this data set came from a group of patients who started their therapy—this goes to the idea of the index date, okay, start of therapy—has the standard of care changed? Has supportive care become increasingly better? Obviously, the answer to that is yes. And so, if you have these contemporaneous mismatches, then can you actually really rely on this real-world data or evidence, either one, as you're applying it to your patient? So, I think if it's for regulatory purposes, certainly you could avoid many mistakes by coming to the FDA early and often, which we always recommend. And if it's you as a clinician, as a health care provider, looking at this collection of data, I think you do have to walk yourself through in a really basic kind of logical process of, “how well does this data apply to the scenario in which I want to use this therapy?” So, index date, selection, timing, patient characteristics, things like that. Dr. John Sweetenham: Yeah, great, thanks. And I'd like to maybe ask both of you for your comments on one final question, and this is circling back to the S2302 study. Intrinsic to the study design and the concept is that the population in this study will be truly representative of the “real world.” My two questions to both of you will be, first of all: What is the gold standard for representative? In other words, what does that really mean to have a representative population of patients with advanced non-small cell lung cancer? And secondly, do you have any safeguards in place in the course of the study designed to make sure that that study population doesn't get skewed in some way so that it becomes unrepresentative of the real world? So, Dr. Reckamp, maybe I can start with you and ask you for your comments about that. Dr. Karen Reckamp: Thank you. I think that's a very good question and something that we grappled with as we designed this study and really did keep coming back to that. So, I think when we talk about representation, most randomized trials don't have broad representation. They are very specific populations that we curate in order to take as much variability out of the trial as possible so that we can investigate just the experimental arm versus standard of care or whatever we're evaluating. And here, we've consciously made an effort to say we want to know how this works in a real practice and make this as generalizable as possible while still being safe. So, we have the premise of keeping patients safe as the number one goal of this trial. And then, we want to look at the survival data. So, we actually did lower the bar a bit and changed our hazard ratio. Our hazard ratio was 0.69% for the phase 2 trial. We loosened that a little bit for the phase 3 trial, knowing that the patients that are coming on to trial are not going to be perfect patients, and there may be a little more coming together of those curves. That being said, randomization is what is supposed to wash away all sins, which has been said many times as we put this trial together. And so, the randomization is really the goal, to utilize the randomization process in order to make sure that there is balance and that we are getting representation on both sides that will help us understand how the investigational arm is really doing in this population. It's not going to be perfect, and we are allowing for performance status 2 patients. But I think we all believe that this is really important because there's a large proportion of patients who have performance status 2 who never go on to trials, but in the real world, we treat them generally with the standard of care options that we use. So, I think this is really important for moving things forward, and will be groundbreaking in that way, too. Dr. John Sweetenham: Great, thank you. And Dr. Singh, just to add to that, will the FDA be looking at this from the perspective of making sure that the study population as a whole—accepting that randomization will hopefully cancel out some of the potential pitfalls there—but will the FDA be looking to make sure that the population as a whole is truly representative of what's out there in the real world?  Dr. Harpreet Singh: We always look at the population. We are always hopeful that, in general, the population is reflective of the disease for which—in this case, lung cancer. I think in this case, we were very hands-on with developing the protocol, and it is our hope and it's our expectation, and I think it very much will happen that you are going to see a very diverse and representative, more generalizable population here. I just want to add a piece to this because remember that traditional randomized clinical trials typically do have a more homogeneous patient population because a lot of this is designed around a de-risking strategy when you're bringing new drugs to market. One of the reasons we felt so comfortable stripping away, as Karen mentioned, no lab criteria. If the clinician says, “I think you're fit for this regimen, go ahead and enroll them.” We pushed for inclusion of PS 2 patients. We, the FDA, did. So, yes, we're going to be looking, but we do really hope that these really streamlined inclusion and exclusion criteria allow for that. And so there's other things too, like race, ethnicity, age. And so it starts with not excluding patients based on perhaps unfair or arbitrary cutoffs like labs. Not to say that performance status is arbitrary. But in this case, if the clinician deems you fit for this therapy, that is between the patient and the investigator and their judgment, which is really part of the element of real-world trials and this pragmatic element too.  I also wanted to add on this idea of diverse representation, we expect there to be a lot of extra, for lack of a better term, noise, in this trial, even though it's randomized. And so, part of the negotiation around designing this trial was the need for an increased sample size to try to account for some of what we expect to be perhaps unequal randomization, perhaps in terms of patient characteristics on either side, perhaps patients lost to follow-up, etc. And so, when we talk about pragmatic trials, one element is that you probably often may need an increased sample size to account for the increase in heterogeneity, not only in your patient population but perhaps in monitoring as well. Dr. John Sweetenham: Well, thank you both, Dr. Reckamp and Dr. Singh, for a great discussion today and for sharing your insights on these developing trends in clinical trial design. Dr. Reckamp and Dr. Singh, we'll be watching closely to see how the trial performs in the coming months and advances the concepts of pragmatic trial design that Dr. Singh mentioned earlier within the FDA. We obviously are very excited to see whether this change in trial conduct will enable you to meet new groups of patients and ultimately improve outcomes for them. So, thanks once again for being with us today. Dr. Harpreet Singh: Thanks so much. Dr. John Sweetenham: And thank you to our listeners for your time today. 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. Find out more about today's speakers: Dr. John Sweetenham  Dr. Karen Reckamp  @ReckampK  Dr. Harpreet Singh  @harpreet_md Follow ASCO on social media:  @ASCO on Twitter  ASCO on Facebook  ASCO on LinkedIn  Disclosures: Dr. John Sweetenham: Consulting or Advisory Role: EMA Wellness Dr. Karen Reckamp: Consulting/Advisory Role: Amgen, Takeda, AstraZeneca, Seattle Genetics, Genentech, Blueprint Medicines, Daiichi Sankyo/Lilly, EMD Serono, Janssen Oncology, Merck KGaA, GlaxoSmithKline, Mirati Therapeutics Research Funding (Institution): Genentech/Roche, Janssen Oncology, Calithera Biosciences, Elevation Oncology, Daiichi Sankyo/AstraZeneca, Blueprint Medicines Dr. Harpreet Singh: None Disclosed

Guest host Dr. Vamsi Velcheti, of the NYU Langone Perlmutter Cancer Center, and Dr. Brian Henick, of the Columbia University Herbert Irving Comprehensive Cancer Center, discuss advances in KRAS-mutated lung cancer in the KRYSTAL-1 trial, and the association of ctDNA with overall survival in the NADIM trial, as well as other key advances in lung cancer presented at the 2022 ASCO Annual Meeting.   TRANSCRIPT   Dr. Vamsi Velcheti: Hello, everyone! This is Dr. Vamsi Velcheti, I'm your guest host for the ASCO Daily News podcast, today. I'm an associate professor and medical director for the Thoracic Oncology Program at Perlmutter Cancer Center at NYU Langone Health. My guest today is Dr. Brian Henick, an associate director of the Experimental Therapeutics Program, and assistant professor of Medicine at Columbia University's Herbert Irving Comprehensive Cancer Center. We'll be discussing key abstracts in lung cancer that were featured at the 2022 ASCO Annual Meeting. Our full disclosures are available in the notes and disclosures of all guests on the podcast can be found on the transcripts at asco.org/podcasts. Brian, it's great to speak with you today. Dr. Brain Henick: Thank you so much, Vamsi, and ASCO Daily News for letting me join you to discuss these abstracts. Dr. Vamsi Velcheti: So, let's dive in. So, it's an exciting ASCO Annual Meeting. And I hope you had a great time at the Meeting. So, let's start off with the LBA9009 and KRYSTAL-1 clinical trial. The study showed the activity of adagrasib in patients with KRAS-G12C mutant non-small cell lung cancer and active untreated brain mets. So, what is the key takeaway from this trial? Dr. Brain Henick: Well, Dr. Sabari presented some encouraging data on this important population. As we know, patients with active central nervous system (CNS) metastases represent a population of unmet medical need who are often excluded from clinical trials. So, it's a credit to the investigators for including this cohort. As Dr. Sabari noted, and as Dr. Goldberg emphasized in her discussion of the abstract, the measured CNS penetration of adagrasib compares favorably with other CNS active compounds from other settings. The overall response rate was 35%, with a disease control rate of 80%. But impressively, the median duration of intracranial response and progression-free survival (PFS) wasn't reached. This certainly seems to be a CNS active compound, and we'll need to see how sotorasib stacks up in their comparable cohort. Ideally, we'd have randomized data to prove superiority over the standard of care, but we may be a few steps away from that. Dr. Vamsi Velcheti: So, Brian, in terms of CNS mets, how big of a problem is it in patients with KRAS G12C mutant lung cancers? Dr. Brian Henick: We know that CNS metastases are a big problem for G12C mutant lung cancer. The rates have been quoted as high as up to 42% of patients. And in particular, as you know, Vamsi, a lot of times trials often don't include, specifically, cohorts with active untreated brain metastases. And so, this is a very unique cohort in that sense. Dr. Vamsi Velcheti: I just want to highlight that we really don't know the differential efficacy of sotorasib and adagrasib in the CNS met population because the trials were CodeBreak 100 and other trials and data readouts from sotorasib did not include patients with untreated brain mets. We did, however, [see] CNS progression-free survival data that go in line with sotorasib. So, it's really important to see that data from sotorasib. Dr. Brain Henick: I definitely look forward to seeing that. Dr. Vamsi Velcheti: So, let's talk about Abstract 8501. The primary endpoint that was presented at ASCO [Annual Meeting] was the pathologic complete response to chemotherapy and nivo vs. chemotherapy as a new adjuvant treatment for resectable stage 3, a non-small cell lung cancer. This was the phase 2 NADIM trial. So, what do you think about this study? And what's your key takeaway from the study? Dr. Brain Henick: Dr. Provencio from Spain presented data from this randomized study as you said, of nivo plus carbo taxol compared to carbo taxol as neoadjuvant therapy for potentially resectable stage 3-A and B non-small cell lung cancer. So, I did want to compare this to the randomized data that we have from Checkmate 816, which interestingly allowed for earlier-stage disease as low as 1-B. And they also allowed for more flexibility in the choice of platinum doublet regimens. This study, NADIM 2, employs 2:1 versus 1:1 randomization, which we saw in Checkmate 816. Another important difference was that NADIM 2 required adjuvant nivolumab for 6 months in the study arm, whereas Checkmate 816 didn't include any immunotherapy in the adjuvant setting, but they allowed for a standard of care chemotherapy. In NADIM 2, the control arm didn't include any adjuvant therapy. In keeping with the impressive improvements over historical pathologic complete response rates of about 5%, this chemotherapy-IO regimen yielded a path complete response (CR) rate of 36.8%. It also showed a major pathological response, which again is defined as less than 10% viable tumor of 52.6%, and an overall response rate of 75.4%. So, it looks like there's a benefit that's happening upfront with the immunotherapy and chemotherapy as opposed to this just being an adjuvant phenomenon. This is also in keeping with data that we saw with Checkmate 816, as well as neoadjuvant atezo plus chemotherapy in the phase 2 study that was led by Catherine Shu and colleagues here at Columbia a few years ago. Overall, this is more encouraging data for the neoadjuvant use of immunotherapy. The earlier immunotherapy marches into the treatment course of patients with lung cancer, the greater the cost of toxicity. So, I think an important thing for us to focus on going forward is trying to develop strategies to better identify the patients that are most likely to benefit. Dr. Vamsi Velcheti: So, Brian, I think from a practical standpoint, now that we have approval for neoadjuvant immunotherapy and adjuvant immunotherapy, we have some practical challenges in terms of how we manage our patients. Of course, the new adjuvant is very appealing because it's only 3 cycles of chemoimmunotherapy, but the challenge though, is a majority of the patients don't have a CR, or a significant proportion of the patients have an ongoing response or significant residual disease at the time of surgery. So, the question then would be what do you do after surgery if they're having an ongoing response? Do you think 3 cycles of immunotherapy are inadequate systemic therapy for these patients? Dr. Brian Henick: It's a really important question, Vamsi. I think until the data is mature, we're just kind of limited by the extent of what the data tells us so far, and then we have to kind of do our best as the treating doctor to navigate the patient's situation. So, tools that we'd still have available to us in the adjuvant setting that are approved are things like chemotherapy and radiation, leveraging things like circulating tumor DNA, I think maybe a promising path forward, as well to help guide strategies there, but I think until the data is mature, it has to be highly patient-focused to figure out what seems to be most appropriate there. How are you navigating those situations, Vamsi? Dr. Vamsi Velcheti: Yeah, as you said, it is very challenging. I think we need more data. And of course, the challenge now is like, if you use immunotherapy in the new adjuvant setting, it's very likely you're not going to get insurance authorization for 1 year of adjuvant atezolizumab. So, we really need studies to optimize treatment paradigms here. As you suggested, maybe circulating tumor DNA (ctDNA)-based approaches to look at residual disease, I think, that would be one great way to do it. Let's move on to the next abstract, Brian. I found Abstract 9001 really interesting. It's a U.S. Food and Drug Administration (FDA) pooled analysis that looked at outcomes of first-line immune checkpoint inhibitors, with or without chemotherapy based on the KRAS mutation status and PD-L1 expression. So, what is your take on this abstract and how do you think this is going to impact our practice? Dr. Brian Henick: So, Dr. Nakajima and colleagues explored the observation from individual trials that patients with KRAS-mutant lung cancer seem to have better responses than wild type with immunotherapy (IO) alone. But the favorability of these responses seems to be abrogated with chemotherapy-IO. We know that KRAS accounts for 25% of oncogene-driven non-small cell lung cancer predominantly at amino acid 12. And with the emergence of direct inhibitors of G12C, understanding the clinical features of these tumors may be critical to inform optimal integration of this new class of drugs and also to make sure that we've optimized treatment algorithms for KRAS patients in general. So, this study's authors at the FDA pulled data from 12 registrational clinical trials that were investigating first-line checkpoint inhibitor-containing regimens and they found no significant difference between KRAS wild type and mutant for overall survival regardless of the regimen used. The best outcomes were seen with chemoimmunotherapy regardless of KRAS status. This retrospective analysis does suggest that the notion of there being lesser benefit from chemoimmunotherapy from Dr. Gadgeel's study might not hold up in the overall population, but I think it raises important questions, like, are all KRAS mutations alike? The absence of KRAS mutation status for a majority of patients included in these studies limits the interpretation of the data. And also, the absence of commutation status makes it a little harder to interpret. And other important questions remain such as how G12C inhibitors will factor in? What were your thoughts, Vamsi? Dr. Vamsi Velcheti: No, I completely agree with you, Brian. I think we need more data and we know that commutation status is a very important aspect in terms of KRAS-directed therapies. And of course, with a lot of promising data from these KRAS inhibitors, there's an interest in moving these drugs into the front-line therapy for patients with KRAS mutations. But I think it's going to be quite challenging to incorporate them into the front-line therapies and we clearly will need better characterization of these patients with KRAS mutant [lung cancer] to further personalize treatment in the frontline setting for these patients. So, let's move on to the next abstract. This is the lung map study, Abstract 9004. This is a study sponsored by the National Cancer Institute (NCI), the lung map study, looking at overall survival from a phase 2 randomized study of ramucirumab and pembrolizumab, what's the standard of care in patients with advanced non—small cell lung cancer previously treated with immunotherapy. So, what were your key takeaway points here from this study? Dr. Brian Henick: So first of all, it's very exciting to see data from this very ambitious long map sub-study yield a positive result. Whereas many of the arms of this study were biomarker-guided, Dr. Reckamp presented the results from pembro plus ramucirumab as compared to the standard of care in unmarked patients with non-small cell lung cancer who had progressed after prior treatment with chemotherapy and immunotherapy. The data seems to suggest that pembro plus ramucirumab may be better tolerated than the standard of care chemo-containing regimens, as the experimental regimen had fewer serious adverse events. Pembro plus ramucirumab had a median overall survival of 14.6 months as compared to 11.6 months in the control arm and this was statistically significant. The PFS difference wasn't significant, but there was a late divergence in the curves. Dr. Bestvina nicely summarized some of the study's limitations such as the mixture of control regimens used, and there were really interesting signals that were found on subgroup analysis, such as benefit in those with mixed histology tumors, STK11 mutant tumors, and those who received chemotherapy prior to immunotherapy. The subgroups deserve further attention in the future. For now, this regimen may be an appealing option as an alternative to chemotherapy for the right patients. What do you think? Dr. Vamsi Velcheti: Yeah, I agree, Brian. I think it's a really promising combination. We've always seen some synergy with VEGF inhibitors and immunotherapy in multiple studies and multiple tumor types. So, we really need to develop better ways to select patients for VEGF combination-based approaches in lung cancer. So, let's move on to another interesting study. This is Abstract 9000. This explores the outcomes of anti-PD-L1 therapy with or without chemotherapy for first-line, metastatic non-small cell lung cancer with a PD-L1 score of greater than 50%. So, this is an FDA pooled analysis. So, what were your key takeaways from this abstract? Dr. Brain Henick: I thought this question was really well suited for a large pooled retrospective analysis and our colleagues at the FDA didn't let us down here. The question really was what's the optimal approach for patients with non-small cell lung cancer with greater than 50% PD-L1 in view of the absence of direct comparisons between these arms in prospective studies? I thought one of the most striking findings from Dr. Akinboro's presentation was the dismally low rate of underrepresented minority patients that were included in these registration trials. As far as the findings for the patients who were studied, although the Kaplan-Meier curves for overall survival showed early separation, the difference wasn't statistically significant. Subgroup analysis revealed a trend towards better outcomes for immunotherapy alone among patients who are [age] 75 and above, suggesting that this may need to be parsed out as a unique population in subsequent studies. But in all, our equipoise as a field on whether to include chemoimmunotherapy-based first-line regimens should persist and should be guided, in my opinion, largely by clinical considerations. Can the patient tolerate chemotherapy? Do you need a rapid response? Are there other things that you thought in hearing all this, Vamsi? Dr. Vamsi Velcheti: Yeah, absolutely. I think I am still struggling with the decision of whether to add chemotherapy for patients with greater than 50%. To a large extent, it's actually a clinical decision. In some patients who have a large disease burden, I tend to kind of opt for adding chemotherapy to immunotherapy in the front-line setting. But of course, we need more data here. And this is actually a very helpful piece of information from the FDA. And as you pointed out briefly, Brian, I think the fact that there are very few underrepresented patients in the pooled analysis, I think kind of speaks to the need for addressing increased diversity in clinical trial accruals. I think this is a great segue to also talk about Abstract 9012, talking about disparities in access to immunotherapy globally. This is a study from India looking at 15,000 patients who were checkpoint inhibitor eligible and who have very low rates of uptake of immunotherapy. This is something that reflects the global team of the ASCO Annual Meeting talking about disparities and improving access to treatments in underserved minority populations here in the United States, and also globally, in the developing world, the disparities in terms of access to care are humongous. So, what are your thoughts, Brian? And also, if you could highlight some of the work that you're doing at Columbia about disparities, I think that would be great. Dr. Brain Henick: Absolutely! I think access to medications is a really humbling topic for those of us who are involved in developmental therapeutics, particularly with the transformational impact we've seen with the advent of immunotherapy over the last decade-plus. Dr. Ravikrishna's presentation is therefore extremely important. He described very low rates of uptake of immunotherapy by indication. And perhaps most strikingly, the discrepancy in uptake by patients' ability to pay for therapy with the vast majority of immunotherapy received by those who are private is very concerning. Even if the definition of restricted access was permissive, for example, I didn't see mention of the cancer stage as an eligibility factor, the fact that this represents a single referral center's data doesn't bode well for uptake elsewhere. So, I think we need to continue to work as a field on prioritizing strategies to help overcome these gaps, but good quality data such as this study is an important first step. And to that point, Vamsi, I'm very excited to be working with you in collaboration on an observational study for patients with lung cancer from underserved minority populations with lung cancer in New York City so that we can better characterize access to care, efficacy, and toxicity in this population. Dr. Vamsi Velcheti: Thank you, Brian. I'd really like to thank you for sharing your valuable insights with us today on the ASCO Daily News Podcast. We really appreciate it. Brian, thank you so much for joining us. Dr. Brain Henick: My pleasure. Thanks for having me. Dr. Vamsi Velcheti: And thank you to all our listeners for joining in today. You will find links to all the abstracts discussed today in the transcript of this episode. 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. Thank you so much.     Disclosures: Dr. Vamsi Velcheti: Honoraria: Honoraria Consulting or Advisory Role: Bristol-Myers Squibb, Merck, Foundation Medicine, AstraZeneca/MedImmune, Novartis, Lilly, EMD Serono, GSK, Amgen Research Funding (Inst.): Genentech, Trovagene, Eisai, OncoPlex Diagnostics, Alkermes, NantOmics, Genoptix, Altor BioScience, Merck, Bristol-Myers Squibb, Atreca, Heat Biologics, Leap Therapeutics, RSIP Vision, GlaxoSmithKline Dr. Brain Henick: None disclosed. Disclaimer: The purpose of this podcast is to educate and 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.

Erica Reckamp serves as the Executive Writer and Content Strategist for Chicago-based career services firm Job Search Like a Pro. Earlier roles include Head/Senior Writer for Global Outplacement & Career Transitioning firm Challenger, Gray & Christmas, Professional Training & Coaching firm Empowered Possibilities, and EQ-IQ Coaching. Erica is a fellow member of the National Resume Writers Association (NRWA) and Career Thought Leaders (CTL).LEARN MORE: jobsearchlikeapro.comLinkedIn/Erica-Reckamp

Imagine an episode of “60 Minutes” mixed with a Ram Dass lecture, but starring your favorite musicians…Enjoy this episode with Justin Reckamp of Mungion, recorded in February of 2020. This is the Weird Music Podcast, where our host Cam Elkins explores the minds of the most creative and influential people involved in the music festival scene. We are very grateful for our generous listeners & sponsors that make this show possible. If you'd like to contribute, feel free to give a tip on Venmo — @Cam_Elkins  Even though psychedelic live music experiences are basically unexplainable… let's give it a try.Subscribe to our Youtube >>> https://bit.ly/2Z007Uq 

The podcast welcomes NA amateur mid laner Aidan "5fire" Reckamp to talk through his playing career so far, his thoughts on LCS, and players to watch in Academy and amateur this summer. Follow 5fire at twitter.com/5fireleague and twitch.tv/5fire Follow Tim at twitter.com/TimSevenhuysen Subscribe on Anchor Support the show on Patreon Join the community on Discord Show Notes 0:00 Intro 2:00 5fire's playing achievements 13:25 Experiences finding a team 20:20 Time with EG Academy 24:43 Best coaching 5fire has received 30:55 LCS summer expectations 42:34 Academy/amateur players to watch for 51:30 Expanding your champion pool comfort zone 55:35 Mid laners in amateur/Academy 5fire respects most 1:00:17 Listener questions 1:00:32 Brandon Brobst: With new mid picks like Lee Sin and new champs Gwen and Viego being strong, what's your process for learning a new champ? 1:02:20 Purliini: Would you ever go to EU for a split and play some regional league and same time climb EUW solo queue? 1:03:25 Stargazingspot: What's 5fire's favourite league to watch? 1:06:18 Outro

On this episode guest and career coach Erica Reckamp talks about how to uncover and highlight your unique value, how to craft content and build a strategy that can help you land a job, job search challenges that professionals often face, and how to overcome them. Erica Reckamp an executive writer & job search strategist at Job Search Like a Pro where she crafts custom content for her clients so that they stand out as a top candidate and land offers that they truly want. LinkedIn: Erica Reckamp https://www.jobsearchlikeapro.com --- This episode is sponsored by · Anchor: The easiest way to make a podcast. https://anchor.fm/app Support this podcast: https://anchor.fm/mondaysshouldntsuck/support

In this episode, Luis Paz-Ares, MD, PhD; D. Ross Camidge, MD, PhD; and Karen L. Reckamp, MD, MS, address questions on MET exon 14 testing and selecting MET-targeted therapies for patients with advanced NSCLC with topics including:Incorporating MET exon 14 testing into standard of careComparison of RNA-based and DNA-based NGS platformsAvailability of RNA-based NGS testing around the worldUsing FISH to quantify MET copy gain/amplificationRegulatory and clinical differences between new, selective MET inhibitorsSafety profiles of type I vs type II MET inhibitorsCounseling patients on management of peripheral edema, a class effect with MET inhibitor therapyInsights on combining MET inhibition with immune checkpoint inhibition therapy or chemotherapySelecting second-line therapy for a patient with MET exon 14–altered NSCLC progressing on tepotinib or capmatinibPresenters:Luis Paz-Ares, MD, PhDMedical OncologyUniversity Hospital Doce de OctubreMadrid, SpainD. Ross Camidge, MD, PhDProfessor of Medicine/OncologyUniversity of Colorado Cancer CenterAurora, ColoradoKaren L. Reckamp, MD, MSProfessor of MedicineDirector, Division of Medical OncologyDepartment of MedicineCedars SinaiLos Angeles, CaliforniaContent based on an online CME program supported by an independent grant from the Healthcare business of Merck KGaA, Darmstadt, Germany.Link to full program, including associated downloadable slidesets:https://bit.ly/2ExadCf

In this episode, Luis Paz-Ares, MD, PhD; D. Ross Camidge, MD, PhD; and Karen L. Reckamp, MD, MS, address questions on biomarking testing and the use of immunotherapy in METex14 mutation–positive NSCLC with topics including:Whether testing for MET  exon 14 status should be standard of careParallel vs sequential testing by DNA-based vs RNA-based NGSCo-occurring driver mutations in patients with METex14 mutation–positive NSCLCOptimal use of immune checkpoint inhibitor–based therapy in the setting of METex14-positive disease, including sequencing with MET inhibitor–based therapyEMA regulatory considerations for the new, selective MET inhibitors tepotinib and capmatinibPresenters:Luis Paz-Ares, MD, PhD Medical OncologyUniversity Hospital Doce de OctubreMadrid, SpainD. Ross Camidge, MD, PhDProfessor of Medicine/OncologyUniversity of Colorado Cancer CenterAurora, ColoradoKaren L. Reckamp, MD, MSProfessor of MedicineDirector, Division of Medical OncologyDepartment of MedicineCedars SinaiLos Angeles, CaliforniaLink to full program, including associated downloadable slidesets:  https://bit.ly/2ExadCf

We’re big fans of the music Mungion makes. Whether its the blend of different styles of music, the general groove, or the fun lyrics, these guys are what jam bands should be about, FUN! There 2017 ended with a bit of a thud, as you’ll soon here, but since the Winter of 2018 these guys have been gigging hard, and Live Fun Vol.1 is a compendium of some of the musical highlights of that tour. We caught up with friend of the show Justin Reckamp to check the pulse of the band coming off Summer Camp Festival last week, and to talk about Live Fun Vol.1 out now. Mungion’s complete tour schedule is available at mungion.com. **First Song:** 00:45 – Basketball (Live) **Interview Begins:** 05:03 **Extro Song:** 42:15 – Que Maste Tu Cabello > Scrambled Legs > Que Maste Tu Cabello Pt. 2 (Live) See omnystudio.com/listener for privacy information.

We were all set to talk with Mungion last week but unfortunately something went horribly wrong for them, so we had to reschedule. Their entire van and trailer were stolen in Detroit just before they were set to head cross country for their first headlining tour. Wisely, they’ve started a GoFundMe campaign, and are putting their best foot forward and continuing with their tour plans. I sat down with Justin Reckamp to get the low down on the band, and their plans moving forward.  You can listen to this episode below, or by connecting and subscribing to one of the podcast platforms here or search your favorite podcast platform for “The Sound Podcast”; Itunes: http://bit.ly/sndpodi TuneIn: http://bit.ly/sndti Stitcher: http://bit.ly/sndsti GooglePlay: http://bit.ly/sndplay Get The Sound Podcast App: http://bit.ly/TSPAPPS See omnystudio.com/listener for privacy information.

Dr. West moderates a question & answer session with Drs. Karen Reckamp and Taofeek Owonikoko on issues of acquired resistance to targeted therapies for patients with advanced NSCLC that harbors a driver mutation.

Dr. West moderates a question & answer session with Drs. Karen Reckamp and Taofeek Owonikoko on issues of acquired resistance to targeted therapies for patients with advanced NSCLC that harbors a driver mutation.

Dr. West moderates a question & answer session with Drs. Karen Reckamp and Taofeek Owonikoko on issues of acquired resistance to targeted therapies for patients with advanced NSCLC that harbors a driver mutation.

Dr. Karen Reckamp of City of Hope Cancer Center reviews the concept of acquired resistance to targeted therapies in patients with a driver mutation and why it occurs.

Dr. Karen Reckamp of City of Hope Cancer Center reviews the concept of acquired resistance to targeted therapies in patients with a driver mutation and why it occurs.

Dr. Karen Reckamp of City of Hope Cancer Center reviews the concept of acquired resistance to targeted therapies in patients with a driver mutation and why it occurs.

Conversations with Oncology Investigators. Bridging the Gap between Research and Patient Care. Interview with Karen L Reckamp, MD, MS conducted by Neil Love, MD. Produced by Research To Practice.

Dr. Karen Reckamp from City of Hope Cancer Center in Duarte, CA describes which patients with advanced NSCLC she seeks molecular marker testing on, and the particular markers she prioritizes.

Dr. Karen Reckamp from City of Hope Cancer Center in Duarte, CA describes which patients with advanced NSCLC she seeks molecular marker testing on, and the particular markers she prioritizes.

Dr. Karen Reckamp from City of Hope Cancer Center in Duarte, CA describes which patients with advanced NSCLC she seeks molecular marker testing on, and the particular markers she prioritizes.

Dr. Karen Reckamp, City of Hope Cancer Center, provides her perspective on the likelihood that molecular oncology principles and targeted therapies will become more broadly applicable for patients with squamous and other lung cancer subtypes.

Dr. Karen Reckamp, City of Hope Cancer Center, provides her perspective on the likelihood that molecular oncology principles and targeted therapies will become more broadly applicable for patients with squamous and other lung cancer subtypes.

Dr. Karen Reckamp, City of Hope Cancer Center, provides her perspective on the likelihood that molecular oncology principles and targeted therapies will become more broadly applicable for patients with squamous and other lung cancer subtypes.

Dr. Karen Reckamp, City of Hope Cancer Center, reviews her thought process in recommending a repeat biopsy at initial diagnosis or after progression for patients with advanced lung cancer.

Dr. Karen Reckamp, City of Hope Cancer Center, reviews her thought process in recommending a repeat biopsy at initial diagnosis or after progression for patients with advanced lung cancer.

Dr. Karen Reckamp, City of Hope Cancer Center, reviews her thought process in recommending a repeat biopsy at initial diagnosis or after progression for patients with advanced lung cancer.