🚨 This may be the most consequential oncology study of 2026. Yes, on par with daraxonrasib. At #ASCO26# we highlighted the 5-year KEYNOTE-942 data for the individualized mRNA cancer vaccine intismeran + pembrolizumab in resected high-risk melanoma. And the numbers were 👀 RFS HR 0.51 5-year RFS: 68.8% vs 49.1% DMFS HR 0.41 OS HR 0.47 (still immature) Amazing data. But 157 patients. Phase IIb. The big question: does it hold up in phase III? Apparently, yes. 🔥 INTerpath-001 randomized 1,137 patients with resected stage IIB-IV melanoma to intismeran + pembrolizumab vs pembrolizumab alone. At the prespecified interim analysis: ✅ RFS met ✅ DMFS met ✅ Statistically significant AND ✅ No new safety signals We don’t have the HRs yet. So some restraint until we see the actual data (also this is a press release, so grain of salt) But why is this such a big deal? Because this isn’t really about melanoma. 🧬 Sequence YOUR tumor 🎯 Identify YOUR neoantigens 💉 Manufacture a vaccine specifically for YOUR cancer 🦠 Train YOUR immune system to recognize it And now that approach has succeeded in a randomized phase III trial. This is actually personalized. And if this platform works across tumor types, the implications are enormous. Daraxonrasib may change how we treat RAS-driven cancers. INTerpath-001 may change how we think about cancer vaccines altogether. 2026 has been an amazing year for oncology advances. 🔥 @OncoAlert @Onco_Nexus @TheGutOncLab

A randomized phase III rectal cancer trial out of China just reported some great results for Locally Advanced Rectal Cancer (and confirms our modern TNT practice). TNTCRT randomized 458 patients with high-risk LARC to conventional long-course CRT → surgery → adjuvant chemotherapy versus CAPOX before, during, and after long-course radiation. Yep. Doublet chemo, all the way through. 3-year DFS: 74.8% vs 66.0% HR 0.67 MFS: 77.7% vs 67.6% HR 0.66 pCR: 26.4% vs 9.8% Big numbers, much win. But the criticism is the comparator. The control arm is not how we treat high-risk rectal cancer in the US. We already know TNT is better than CRT → surgery → adjuvant chemotherapy based on OPRA's modern benchmark. With CRT followed by consolidation FOLFOX/CAPOX, 3-year DFS was 76%, essentially the same as the 74.8% seen here. But OPRA also comes with the added benefit of TME-free survival of 54%. I think what is still impressive is the scale and speed of this trial. The Chinese trial infrastructure is fully operational and anyone in drug development should take note. @TheGutOncLab @OncoAlert

Great experience working on this editorial. Always love when I have an opportunity to comment on the absolute magic that is Radiation Oncology. RTOG 1010 may not have been a success in the conventional sense, but the lessons learned are absolutely worth reflecting on. Thanks @NiuSanford @UGrewalMD and @TimothyJBrownMD ! @TheGutOncLab @Onco_Nexus @OncoAlert

What should patients (and the physicians guiding them) know when considering a clinical trial? In this episode of @TheGutOncLab, Dr. Nicholas Hornstein (@GIMedOnc), Dr. Timothy Brown, MD MSCE (@TimothyJBrownMD), & Dr. Udhayvir Singh Grewal, MD (@UGrewalMD) unpack how to evaluate trial design, treatment phase, control arms, potential benefit, and the realities behind survival endpoints. A practical conversation for clinicians counseling patients and for patients trying to better understand their options:

Clinical trials are among the most opaque parts of modern medicine. They can be dense and difficult to understand for clinicians, let alone patients. So, @TheGutOncLab recorded an episode designed to make clinical trials a little more approachable. Not just what they are, but how patients can find, evaluate, and enroll in them. This episode is geared more toward patients than clinicians, but we hope it is helpful for anyone looking for an entry point into the world of clinical trials. Video Below: Spotify: @OncoAlert @Onco_Nexus @oncodaily @cancerGRACE

Hear me out. On paper COMMIT is a "Positive" trial. It is also a spectacular demonstration that Atezolizumab monotherapy should never be used for metastatic MSI-H CRC (we can talk about adjuvant). COMMIT was a randomized first-line study in metastatic MSI-H/dMMR CRC. It began as a 3-arm trial of: • mFOLFOX6/bevacizumab (this sucks) • atezolizumab alone • mFOLFOX6/bevacizumab/atezolizumab After KEYNOTE-177 changed the standard of care, the chemotherapy-only arm closed after 20 patients. The trial continued with 82 patients randomized between atezo alone and the four-drug combination. The headline is that adding FOLFOX/bevacizumab to atezo improved PFS: HR 0.42 Median PFS: 24.5 vs 5.3 months ORR: 86% vs 46% Primary progression: 2.8% vs 32.4% The truth is Atezolizumab PALES in comparison to its contemporary PD1/PDL1 agents in this setting. Single-agent atezo: 12-month PFS 35% 24-month PFS 32% For comparison: Pembrolizumab in KEYNOTE-177: 12-month PFS 55% 24-month PFS 48% Nivolumab in CheckMate 8HW: 12-month PFS 63% 24-month PFS 56% This is not evidence that every patient with metastatic MSI-H CRC needs chemotherapy, bevacizumab, and immunotherapy. It is evidence that NO ONE SHOULD BE USING ATEZOLIZUMAB IN METASTATIC MSI-H CRC. And now, drumroll please… The only positive randomized adjuvant immunotherapy strategy in stage III dMMR colon cancer is ATOMIC: FOLFOX + atezolizumab. That makes COMMIT more than a roast. It raises a important question about ATOMIC. Should we be using Atezolizumab in the adjuvant setting? Do we need to be giving chemotherapy here? Looking forward to what others make of this but this is the real question. @TheGutOncLab @OncoAlert @oncodaily

New episode of @TheGutOncLab . With a twist: we got a surgeon on. 🔪 Dr. Robert Martin joined @TimothyJBrownMD and me to talk colorectal cancer liver metastases. CRLM is one of the few spaces in metastatic GI oncology where “curable” is still on the table. But the window is narrow, and biology matters. A few highlights: 🔪 The question is not just “can we remove it?” but “how and what should we remove it?” 🩸 ctDNA is getting hard to ignore, but it should not automatically mean “more chemo forever.” Repeat it. Watch the kinetics. Get the right imaging. Discuss as a team. Surgery with biology-first thinking. New episode out now with Dr. Robert Martin, @TimothyJBrownMD, and me. OncoNexus (Out Now): Spotify (To Be Posted 7/27): Apple (To Be Posted 7/27): @UGrewalMD @OncoAlert @Onco_Nexus

This is the daraxonrasib news I’ve been refreshing the RevMed site for! The NDA has been accepted for FDA review. And before anyone says it: no, this is not “late.” NDA packets are enormous. Clinical data, CMC, safety, labeling, subgroup analyses, QA, regulatory back-and-forth. It takes time to package a drug for FDA review, especially when the goal is not “nice phase 1 signal” but actual approval. Now the timer starts. ⏱️ Why does this matter? An oral RAS inhibitor with phase 3 PFS and OS benefit is a big deal. I think we've all said that enough by now. Now the FDA gets to do what it has said it wants to do: Get life-saving drugs into patients’ hands as quickly as possible (outside of an EAP program). FDA clock officially started. ⏱️ @TheGutOncLab @OncoAlert @oncodaily @Onco_Nexus

How often does a company stop an actively enrolling global phase III trial and open an entirely new registration study? Well, it happened last week. Agenus is moving from BATTMAN to ROBBIN (which certainly has some ethical implications for starting/stopping a study I won't comment on). BATTMAN was testing BOT/BAL against best supportive care in refractory MSS metastatic colorectal cancer. An important question, but a best supportive care control was never likely to gain traction in the United States. ROBBIN moves BOT/BAL where it may have its best chance to work: previously untreated, high-risk stage II/III MSS colon cancer, before surgery and while the primary tumor remains intact. The rationale borrows from FOxTROT and builds on early neoadjuvant immunotherapy work from MSK and others like @pashtoonkasi . The early BOT/BAL data are compelling: • Pathologic response in approximately 60–70% • Major pathologic response in ~35–40% • pCR in ~30% Those are extraordinary numbers for MSS colon cancer and outperform the chemotherapy experience from FOxTROT. ROBBIN will randomize 850 patients to short-course neoadjuvant BOT/BAL followed by standard care versus standard care alone, with event-free survival as the primary endpoint. Will the pathologic responses translate into fewer recurrences? I think there is a real chance they will. The tradeoff will be toxicity. Grade 3 colitis/diarrhea occurred in 13% in one of the early cohorts, although there were no grade 4 events and almost no impact on surgical timing. So yes, you can still smell the colitis. But it may be worth it. @TheGutOncLab @Onco_Nexus @oncodaily @OncoAlert

New episode of the @TheGutOncLab ! Pancreatic cancer is finally be entering a true era of targeted therapy (and no, this isn't just another discussion of RAS, although it does come up). In this episode of we have special guest and queen of pancreatic cancer, @KReissMD who join myself, @TimothyJBrownMD, and @UGrewalMD to discuss why 2026 feels different in PDAC. BRCA/PALB2-directed treatment. PARP maintenance. The next wave of RAS-targeted therapies. The pipeline is moving quickly, and for the first time in a long time, there is real momentum beyond chemotherapy. 🎧 Watch the full episode (with video) on OncoNexus: Spotify: @Onco_Nexus @OncoAlert @oncodaily

Top Trending GI Cancer Oncologists in Q2 2026, curated by @Larvol CLIN ranked by views on oncologists posts on 𝕏. Explore more about oncology conferences, top trials, and reactions from oncologists: #LARVOL# #CancerResearch# #CancerData# #Oncology# #OncologyInsights# #ClinicalTrials# #ClinicalOncology# #GICancer# #GastrointestinalCancer# #GICSM# #ColorectalCancer# #GastricCancer# #LiverCancer# #PancreaticCancer# | @Aiims1742 | @marklewismd | @arnavmehta3 | @GIMedOnc | @Erman_Akkus | @ilyassahinMD | @ronanhsieh | @GillSharlene | @DraMartinezLago | @DaisukeKotani

#ESMOGI26# An interesting exploratory analysis from ATOMIC asks an important question: How much chemotherapy do patients receiving adjuvant FOLFOX + atezolizumab actually need? (Remember, this is our only adjuvant prospective study in MSI-H CRC and is with FOLFOX + Atezolizumab vs FOLFOX. If you can catch these patients before surgery, almost certainly better to treat neoadjuvantly). Quick takeaways: • Patients receiving >6 cycles of FOLFOX appeared to derive the greatest DFS benefit from the addition of atezolizumab (adjusted HR 0.45). • That benefit was not apparent among patients receiving ≤6 cycles (HR 0.84), although this subgroup was relatively small. • Receiving ≥12 cycles of atezolizumab was associated with numerically better DFS than shorter treatment, but this analysis is difficult to interpret given treatment discontinuation for toxicity and other confounders. My interpretation: This actually makes biological sense. Atezolizumab has consistently appeared less active than PD-1 inhibitors in MSI-H CRC. If that's true, then maintaining adequate chemotherapy intensity may be particularly important in this regimen. I don't think these exploratory data answer whether 3 months of CAPOX is sufficient in dMMR disease. If anything, they reinforce that ATOMIC should probably be viewed as the regimen that was studied, than the exact regimen used in clinical practice. Slides nabbed from @GillSharlene @TheGutOncLab @OncoAlert @Onco_Nexus @ESMO

#ESMOGI2026# Surprising news for mCRC out of ESMOGI. KRYSTAL-10: Adagrasib + cetuximab misses its primary endpoint in 2L KRAS G12C mCRC. After the accelerated approval and encouraging activity from KRYSTAL-1, many expected dual KRAS/EGFR inhibition to outperform chemotherapy in the second line. That didn't happen. Quick hits: • Primary endpoint (PFS): Negative • mPFS 7.5 vs 8.1 months • HR 0.89 (95% CI 0.71-1.13) • Response rate dramatically improved • ORR 47% vs 16% • CR 7% vs <1% • No improvement in OS at the final analysis despite the higher response rate. So what happened? This is a reminder that response rate ≠ durable disease control. Nearly half of patients responded, but those responses did not translate into longer PFS or OS compared with modern chemotherapy. Targeted therapy works, but mCRC can overcome via resistance mechanisms (such as via massive KRAS upregulation). Will be interesting to see how novel degraders come into the mix here... Remember, this is a first gen KRASi, the future is still bright here. What does this mean for clinic tomorrow? Honestly, I still love a chemo-free option that is at least on par with chemotherapy. This isn't the end of KRAS G12C in CRC. Far from it. The focus now shifts to moving targeted therapy earlier, where combinations with chemotherapy may produce deeper, more durable responses before resistant clones emerge. Multiple frontline studies are already underway. @TheGutOncLab @OncoAlert @Onco_Nexus @myESMO

#ASCO26# This one is special. This is the hottest paper of 2026 and potentially in the history of pancreatic cancer. Let’s dive in. RASolute 302: Daraxonrasib vs investigator’s choice chemotherapy in previously treated metastatic pancreatic cancer Abstract LBA5 (soon!) Presentation: May 31, 2026, 3:21-3:33 PM CDT For decades, pancreatic cancer has been where good ideas go to die. We have optimized chemotherapy. We have sequenced chemotherapy. We have celebrated modest gains. But the central driver of PDAC has always been sitting there in plain sight: RAS. More than 90% of pancreatic cancers have oncogenic RAS mutations, and until recently, we had essentially nothing direct to do about it. Daraxonrasib is an oral RAS(ON) multiselective inhibitor targeting the active GTP-bound state of mutant and wild-type RAS. And in RASolute 302, it delivered. Quick hits: 📌 Phase 3 international randomized trial 500 patients with previously treated mPDAC Daraxonrasib vs investigator’s choice chemotherapy 🧬 RAS G12 population 91.8% of patients had RAS G12 mutations 📈 OS in RAS G12 population 13.2 vs 6.6 months HR 0.40 P<0.001 📈 OS in overall population 13.2 vs 6.7 months HR 0.40 P<0.001 📊 PFS in RAS G12 population 7.3 vs 3.5 months HR 0.45 P<0.001 📊 PFS in overall population 7.2 vs 3.6 months HR 0.49 P<0.001 🔥 12-month OS Overall population: 53.2% vs 17.3% ⚠️ Toxicity matters, but this was not just more efficacy for more toxicity Grade ≥3 AEs: 61.8% vs 69.6% TRAEs leading to discontinuation: 1.2% vs 11.2% This is the kind of survival curve we almost never get to see in pancreatic cancer. This validates RAS(ON) inhibition in the most RAS-addicted major cancer. It takes a target we have talked about for decades and turns it into a clinically meaningful survival benefit in a randomized phase 3 trial. The next questions come fast: 1L combinations, maintenance, perioperative disease, sequencing, resistance, toxicity management, and whether this becomes a new backbone. RAS is here, and it couldn’t have come sooner. @TheGutonclab @UGrewalMD @TimothyJBrownMD @OncoAlert @Onco_Nexus @ASCO @NazliDizman @LauraAlderMD @DVAraujoMD @DrBarbiOnc @LauraEsfeller @FunchainMD @YGaritaonaindia @DrSAHaddad @jgong15 @iandresmeraz @SakditadMD @RamilaShilpakar @RohitBanwar @lungoncdoc