ASCO 2026 GI Highlights: EMERALD-3, FIGHT-302, CIRCULATE, MATTERHORN

Hello and welcome back. I'm Rohit Gossane, a community medical oncologist, and here with my brother and co-host Rahul Gossane, another community medical oncologist. And we are the oncology brothers. With our ongoing ASCO 2026 conference highlights, we are focusing on GI studies today. We had a chance to touch on Razzaloo 302 in pancreatic cancer space with Dr. Wolpen in a separate episode. And here today we are focusing on four other studies that should be on our radar from GI space. For this, we are excited to welcome back to Nina Vigia from Fox Chase Cancer Center. Nina, thanks so much for joining us. Thank you so much. It's always a pleasure to be here and discuss what's important and what's going to come to clinic tomorrow. And that's what you guys excel at. So I'm excited. Nina, welcome. Another exciting ASCO in the books. Rohit, you brought up Razzaloo 302. Besides that, there were still a lot of studies that were causing buzz here at ASCO. So today, let's focus on those studies. We'll start off with Emerald 3 in HCC, then off to Collinjil, Carcinoma with 5302. After that, let's touch on CTDNA in colon cancer, given circulate update, and then to close off, we'll touch on Matterhorn study. All right, so to start off Emerald 3 study. This is looking at intermediate HCC. You know, in metastatic settings, upfront we have a Tizobeth or Dervatrami. If we were to use Dervatrami based off stride regimen, we primed the disease with one dose of tremi along with Dervalimab, and then we continue with Dervalimab thereafter. Here in Emerald 3, we're looking at stride like regimen with taste. Nina, can you touch on the study and its findings here? So this was like a continuation of the studies that we've been put out of the Emerald 1 was presented before, and now we have Emerald 3. In this particular study, it was four patients who do not have extra hepatic disease. So they have undersectoral disease, but it's not extra hepatic, where we traditionally use embolization procedures, tastes, why 19 different ones. Here, what they did was trying to amp the effect of embolization by adding different regimens to it. They had three different arms. The first one was chemo embolization plus lendvetment, which is a Vegev TKI, and the stride regimen that you just introduced us to. The second arm, they took away the lendvetment, and just said, well, maybe just immunotherapies needed, so it's immunotherapy plus the taste. And the third arm is what we traditionally do, which is taste alone. So typically for these patients, we do taste, and we're trying to see if like, you know, bringing what we're going to do after now going to make a change. You know, the question of now versus later, these all therapies are something patients will get along the course of their disease, but can we optimize therapy by giving everything up front, and so that most patients get better for the treatment, and ultimately the two better outcomes. The primary endpoint of the study was a little confusing. I think that's a take a little minute is because what they wanted to look at was the overall survival between the standard of care, which is the taste, and then the other two regimens. So the other two regimens are not compared to each other, but they are compared to current standard, which is the taste. And the way they built it that they would look at the PFS, then the OS, and then the PFS with the stride taste versus taste, and then ultimately the OS of that. So as you see here, they expected, I don't think anyone was surprised, right? You bring it to therapies that you're doing along the line, and you give them together, you see improvement, right? You've seen this with other Emerald One study, which was just let that dip alone. There are multiple different kinds of studies across the country that show the similar things that progression free survival improves when you combine taste with something else. That's the point. You combine it with stride, as you can see here, this was actually not statistically compared yet, because they have to do some other comparison before they get to it. But the one that was statistically significant was the stride, let vet nibb was taste versus taste. Like give them the kitchen sink versus taste alone improves survival from 10 to 13 months. So it improved, but just a little bit, as you can see here, response rate improved in both regimens. The question that comes up is not sure what length vet nibb was adding because length vet nibb plus taste versus taste was 13 versus nine months and taste versus stride was 13 versus 8.1 months, too. So not sure what the length vet nibb added in the next slide. We see the toxicities were what length vet nibb added, right? So toxicities is something you add that regimen as you see that the greens is all what's stride length vet nibb is. That's the toxic part increased toxicities like 70 80% compared to 20% with the traditional taste that we had seen the rate of great three beds. So it increased toxicity significantly. The next step, the bigger question is does it affect OS like giving everything together? Does it make people live longer? And we have to wait a little. There's a trend that they're showing that's going to do, but we don't have those results yet to know. So will that change practice today or not the question? I think I don't think I'm ready to do the stride length vet nibb and taste yet definitely not the stride past taste is something that a lot of people are trying to incorporate in their practice to some degree because they're multiple studies that show PFS benefit. I don't think it's going to be added as a standard of care yet until we get OS results from these studies in their trending, but if you look at the prior studies in these area, all of those were trending, but then ultimately were negative. So I'm cautiously optimistic. And you will have to wait for the overall survival benefit here. Nina, we all acknowledge that this is a multi disciplinary approach where we are always questioning that taste, tear or SBRT even combined with this systemic therapy. What is your approach in general when this multi disciplinary to report is happening because I tend to rely more on SBRT than tear as well where taste is again now getting outdated with the utilization here. So there's a NRG study right now, which is combining a tazabab and SBRT. That's a study exactly answering the question that you're asking that when these studies were designed, taste was predominantly used, but now most people use by 90 or SBRT in practice. I think in our clinic when we have patients who have locally advanced disease, understandable, but they have a very high P, et cetera, we tend to start with systemic and then consolidate with taste rather than do taste plus stride, although from the get go. But that's how we've been doing it practically. Having said that, I think different, it's just basically every institution picks and shoes will be a bit local therapies and they combine the systemics with it. With every added therapy, there are talk studies associated with it at the end of the day, patient shared decision making and tying that multi disciplinary approach. All right, we will along to our next study fight three zero to this was presented by Dr. Tony Bikai, so looking at FGFR inhibitor upfront in frontline setting today, at least the current standard care is still chemo IO here for FGFR was rather compared to chemotherapy alone as opposed to chemo IO. Nina, can you touch on the study design and its findings and importantly the clinical implications? Yeah, so I think we know we all know that FGFR to directly therapies work for this disease. The problem with the study was that it requires the availability of the results to start treatment patients could get one cycle of chemo, but in reality, not a whole lot of patients could get on the study. They actually had screened 4,000 patients to get their very few patients on the study and that cannot just be explained by the lack of this by marker because it is present in a drug biologic carcinoma at a 20 25 30% rate. So I think the harder part is like how to implement it. So in this particular study, frontline patients got either chemo therapy with cisplatin gym side of being versus chemo get never if they had an FGFR tool re-arrangement. They were allowed to have one cycle of chemo so in clinical practice if you were patient and you start them on chemo and you get the results of FGFR to testing in their positive that a patient should be considered for the results that we see from the study. So unfortunately the study closed early because they couldn't accrue enough patients again all the issues associated with getting biomarker testing in this really frail population. So if you look at the results for this study, you know, it was very interesting to see as you see here the pomegranate arm was better, slightly better 8.3 versus 6.8 months and the hazard ratio was about 0.58. So very good hazard ratio which actually suggests that these patients, even the median wasn't as good, but they had like a longer term response to it which led to the increase hazard ratio was very significant. Now the problem is it's not statistically significant overall because the study didn't meet the number of patients it's needed. What's important to see is a response rate like the response rate of the study were over 40% compared to chemotherapy it was only about 15%. So that's an important finding so if you need a response you need this and then if you look at toxicities, pomegranate is an oral drug. It has you know, veered side effects, the hyperphosphatemias and the hand foot syndrome and the eyes issues that we have to deal with, but other than doesn't have the typical chemo side effects. So I think these are all important considerations. In my practice today, I think the harder part is trying to get these results in time for testing. So incorporating liquid biopsy before you start treatment is a very important thing so that you can get FGFR to rearrangement results. And if they're positive, I think even though this data was not significant, you really have an option to do this in case your patient has a weird side effect or is it into tolerate frontline therapy. Always remember the cis gem here was without the IO that's the compare around current compare around and maybe that was included that difference that we're seeing in benefit maybe obliterated to some degree. So I think both are great options chemo IO or FGFR to direct a therapy. I just want to make sure that I always think of my next step when I'm on my first step. So make sure you order those tests and get those results fast because it's a very effective therapy. But in the future, I think it's a very important thing to do. that will only be effective if we're able to give it to the patient. So, haven't ready. I just think that this study is highlighting a few things. First, the importance of NGS and biomarker testing. I think that's very critical. This is a tough disease to treat, but so if we're able to find that actionable mutation, we can dissect the data a little more. Are you going to use it in frontline settings or second line, but it's giving you that extra treatment option. And then again, you brought up liquid NGS. I think that's very important. That's sad, but if it ends up being a low shedding tumor and that CT DNA liquid is negative, make sure we're going back to that tissue to confirm that it's truly negative. As if now, I still think that IO with chemo ends up being our standard of cure here, but for that patient where I can't use IO or chemotherapy, in that case, if you have that FGF or mutation, this might be the right option. Are you touched on some of the side effects for us to keep in mind as a class here, diarrhea, fatigue, ocular toxicities, and hyperphosphatemia is important? All right, now on to circulate study. Can you touch on this study and based on the findings here? Have you changed your practice? I think it's a form of my practice is how I will start it by. So I think CT DNA has time and again been proven to be a very prognostic marker. I think we can move past that point. The question is how can we use it better to guide our treatments? So in this study, this was only stage two colon cancer patients. So if you remember long time ago, we also had the Cobra trial in US, which also tried to study this particular question in stage two colon cancer, whether we can use CT DNA, but here the user tumor informed CT DNA. And what they found was patients who were CT DNA positive versus negative were randomized to get Adrien chemo versus observation and observation versus off study. Like that was a very confusing thing what they did, but that's how the study was done. It was not done in US. It's different than how we are. We typically do it. But the important point was here that patients were blinded. So if you're CT DNA negative, you were blinded to the results of it that you could go and observation or go of study. Now what they found in this study, the problem was out of all the patients that were tested, 1500 or more patients were tested, only 2.9% for CT DNA positive. So it had a very low rate of CT DNA positivity that actually affected the results of the study that we saw. Because if you only have 15 patients that are CT DNA positive, it will be hard to infer if that actually made a difference of how you treated them. So keep that in mind. But when they looked at it, typically CT DNA positive worse outcomes. They had time to recurrence was less. They had 62% for year recurrence. If you're treated with chemotherapy and you were CT DNA positive, you actually did pretty well. There was only a 19% for year recurrence rate. And the CT DNA negative only had a 12% see, you know, recurrence rate. So these are important numbers when you educate your patients that hey, we are stage two, we're going to do CT DNA testing for you. What is the chance that your cancer will come back even if you're CT DNA negative? I usually coded between 10 to 20% and this study falls in that category. And if you're CT DNA positive, I say no observation, it was 62% in the stage two patient. Again, not every patient that was CT DNA positive recurred in three years. I don't know what's going to happen in the future. But the three year recurrence was 62% not 100% in that group. So always have to keep that in mind. But the CT DNA positive group, which was treated with chemotherapy, their outcomes were much better. As you see in the third slide here, that the CT DNA negative group had a three or DFS of 87%. Patients who were treated with chemo had a three or DFS of 61%. But CT DNA positive patients who did not get chemo, it was only 38%. So giving chemotherapy to the CT DNA positive group patients helped and kept them disease free for longer. So I think what I learned from this study, it affirmed my practice that if I have a stage two patient, I have started incorporating CT DNA testing into the stage two group. We have the dynamic study from before, which showed us that if you're negative versus positive, if you just base your decision on that, you actually end up giving chemotherapy to less people, nearly half of a number of people that you would have otherwise. This particular study confirms that if you're CT DNA positive, giving chemo helps. So both of these help me. And if I have a stage two patient, and they have no other risk factors, but CT DNA is positive, I am going to give them chemotherapy. So it's like one of those high risk features that we call for CT DNA. And I typically prefer dual agent chemotherapy if they are CT DNA positive in this side. If they are CT DNA negative, but they still have a high risk feature of like obstruction perforation, I ignore the CT DNA results. I still give them chemo. I consider CT DNA as a piece of the puzzle, not the sole decision maker. Thanks for summarizing that Nina. Just to summarize here, for that MSI high disease in stage two setting, I'm not relying on CT DNA because it's a low risk impact there. As a result, not doing chemotherapy. For MSI low disease is where the utilization is. If CT DNA positive, relying on chemotherapy, and if not, and know the risk factors present, CT DNA negative, no chemotherapy. And again, despite all this where we stand, there is still quite a bit of confusion. Now Nina, this was for stage two. How are you utilizing this in stage three or stage four setting outside of clinical trials, especially for that stage four patient where you've given six months of therapy, patient had metastatic disease in lung or liver, which has been resected. Any role of CT DNA there? I think yes, it's an evolving space. We have clinical trials in that space, yes. Right. But in my clinical practice, I don't do it as a blanket for everyone. I do it on a case by case basis. And the way I do it, like for example, a stage three patient who is MSI high. They come to me after they've had their surgery, and now I would either be doing atomic regimen for them, worse, you know, not. And usually the MSI high patients are the 80 year old women who get sporadic MSI high population. And it's hard to give chemo and like full-fogs, but IO, you cannot give them five FU alone. That's something you don't do for MSI high patients. What would you do? You could do IO alone. Or you do one dose of full-fogs, and then go to IO alone. But there I use CT DNA very happily. If you're CT DNA negative, I tend to do two tests. Not just one. The sensitive two tests rises from 50% to 80%. If you have two tests that are negative. And once you get one test, the second one comes back very quickly. So I tend to do it three and seven weeks that our dynamic was done too. You have results from dynamic three study that actually CT DNA testing did not help. And you couldn't de-escalate or escalate based on the results of that study. And that's the only study we have that's perspective right now. So I don't routinely use it. Definitely don't use it for more escalating in a regular population. But if I want to de-escalate for other reasons, I use it to conform my decision. I rarely escalate based on just these results. - Again, there's a lot going on here, right? It's also that clearance, it's not just positive. Was it tested before surgery? What's the status there? After surgery, what's the status there? And again, we can spend the whole day just talking about this. But personally, I feel like the more we talk about this, the more confused I get. Because the data and clinical practice around this all over the place. - Five people and exactly 20 different decisions. And the same person may want to order for everybody on one day and three days later, not. But I am still in the population who goes by the book and there is no known data that's positive, that's telling me that escalating or de-escalating based on it is appropriate. So I just use it on a case by case basis, not everyone. - Absolutely. All right, now on to our last study, Matterhorn Study. This was initially presented last year at Asco Plenary with Derva Float, a front then surgery, followed by additional Derva Float and post-op settings for that resectable GE Junction or gastric adenocarsenoma. And you know, I hear at Asco 2020-26, we're seeing an update from Matterhorn. What can we learn from this update? And in your clinical practice, do you check PDL1 score for that resectable disease? - So yeah, so this particular study, right? It had patients, it had all comeers in it. So this particular study at every patient, anybody who's with stage two, three or four, eight, like just live, no positive or T-four disease, those patients could get perioperative chemo therapy with Flod and Derva Lumap and then maintain the Derva Lumap for a year. So that was the idea of this particular study. Very clearly showed that this is a systemic disease, right? That's the point of Matterhorn that yes radiation may help, but people die from distant disease here. That's why intensifying therapy for distant disease actually helps outcomes. We saw it improved overall survival, improved overall survival, like all of these were improved significantly, as you see in these results here, like the EFS went from 11 to 22 months in this study, which is pretty impressive. If you start looking at the tail of the car's right, you start seeing them at 24 months, you go from 30 to 45% of the event-free survival, which is pretty amazing and that just maintains for a very long time, even at 36, you're seeing the same numbers as you were seeing at 24. So that is very exciting, very good for our patients. Now the question is, right, is the benefit, majority of the patients on these studies were PDL-1 positive, more than 75% of the patients were. And is the effect being driven just by PDL-1 positive patients or is it actually helping the PDL-1 negative population? It's still a question that is not answered statistically because the number of patients that were PDL-1 negative were so small that you cannot make assumptions just based on the results that come from this study. So whenever in oncology, unless we can prove it, we give patients benefit of doubt. That's how I practice. The reason I check it's our offer to everybody, the reason I do check it is that if I run into any grade 1AE, would I continue with the risk of become that grade 1 becoming grade 2 or not? Sometimes patients just get grade 1 diary or they had an immunitis episode, was grade one, two and they got better should I re-challenge them or not? My risk-taking behavior depends on what is the rate of a pausivity in that patient and that's why I check it. I don't check it to initiate therapy. I think the update from the study basically they just presented longer follow data from the study. As you can see here maintained pretty much everything that we had known initially, right? The event free survival initially was 11 versus 22 maintaining that. They were looking at data. They were trying to show us because we know that flood is a drug regimen that everybody cannot get. Right? Patients get some part of it. Some patients get other part of it. The bottom line is no matter how you do it, it helps. So the bottom line was yes, not everybody can get flot, not everybody can get flot for eight cycles, but whatever you can give to them, do it, do it, flood IO, systemic therapies, the key in this disease. Ultimately, I think as you can see here, giving the drug helps. Indeed. And we have argued about even immunotherapy is it needed in the tail end of adjuvant setting at all. We have done that in lung press. We continue to argue how much is it adding in adjuvant setting, but as of now we are seeing that we should still continue to valumaf for total one year time. Well, Nina, we have covered quite a bit here. Biggest story at Ask a 2020-26 was around pancreatic cancer, but besides that, we still have a lot of data to touch on. Nina, thank you for taking the time to walk us through these studies. For those tuning in, let's go over a quick recap from today's discussion. In today's discussion with Dr. Nina Vigia Varghia, we touched on four studies in GI malignancies from Ask a 2020-26. M-Roll-3 in HCC, 5302 in Colngio carcinoma, circulate update to touch on CTDNA role in colon cancer and Matterhorn update to discuss periop chemo IO and postop chemo IO in that resectable GE junction and gastric adenocarsinoma. We covered Resolute 302 in a separate discussion. We also touched on M-Roll-3 that is TASE with dervalamab and one dose of tremolimamab, like we have seen in metastatic HCC where we use one dose of tremolimamab and then ongoing dervalamab as per stride regimen. Here we are seeing positive PFS data. I speculate this will likely get approved and multi-D discussion around this option is going to be extremely important. Then we touched on Fight 302 study for FGFR inhibitor in front line setting for a small subset which might be a potential option. As in this study, we see Pemigatinib improved PFS when compared to chemotherapy alone. There will again, this was with chemotherapy being comparison where the stannular care is chemo IO. Then off to circulate study, here we saw an update which continues to show that if CTDNA is positive after surgery in early disease, this is a very poor prognostic marker. Chemotherapy in adjuvant settings here has improved outcomes but this still remains a tough problem to tackle. Then to close, we touched on Matterhorn study which showed that patients that complete their full course of post-op therapy had better outcomes. This is not surprising but it continues to reiterate that dervalumab flot and pre-op and post-op settings followed by dervalumab is our current standard of care and we need to try our best to keep our patients on this regimen as long and as safely as we can. Thanks for tuning in. We look forward to seeing you in our next episode where we continue with conference highlights, treatment algorithms, challenging cases and talk-check discussions. We are the oncology brothers.