Physician reactions and the comparator debate
After the abstract release, several physicians compared INTerpath-001 with SWOG S1801, where neoadjuvant plus adjuvant pembrolizumab was tested against adjuvant pembrolizumab alone. Others pointed out that the two trials enrolled different populations and used different endpoints. The posts below are full and verbatim, newest first, and linked to the originals; they run from ESMO 2026 week (October 17–24, 2026) back to the August 2026 topline announcement.
𝕏🔴 Avrupa Onkoloji Kongresi (ESMO 2026)’nde açıklandı! Malign melanomda immünoterapiye, kişiye özel hazırlanmış mRNA kanser aşısının eklenmesi kanserin tekrarlaması veya ölüm riskini %42 azaldı Uzak metastaz riskini de %38 azaldı. Faz 3 INTerpath-001 çalışması. #cancer #oncology #ESMO2026
𝕏🆙#ESMO26 Presidential Symposium I 🔥INTerpath-001: Phase 3 Study of the mRNA-Based Individualized Neoantigen Therapy (INT) Intismeran Autogene (Intismeran) Plus Pembrolizumab (Pembro) vs Pembro Alone for Adjuvant Treatment of Resected Stage IIB-IV Melanoma (MEL) 🎙️ @ProfGLongMIA 🔢LBA1 🎯Met Primary Endpoint: Significantly Improved RFS 🎯24-Mo 82.2% vs 70.0%, HR 0.58 🎯DMFS HR 0.62 🎯Grade≥3 AEs 23.6% vs 20.3% ☑️NCT05933577 🔗 https://t.co/Lb6tzuMm0z @OncoAlert @Larvol @myESMO
𝕏🌟AND finally, #ESMO26 wouldn't be complete without some of the HEAVY hitters. I expect these data to change practice! 1⃣Tarlatamab plus durvalumab (durva) vs durva as 1L maintenance (1LM) therapy following durva, platinum, and etoposide (1L durva + EP) in extensive-stage small cell lung cancer (ES-SCLC): Primary analysis of the phase 3 DeLLphi-305 trial. I fully expect this trial to establish DLL3 TCE as the dominant first line strategy in SCLC and will likely be practice changing. 2⃣Krascendo 1: Efficacy and safety of divarasib (diva) vs sotorasib (soto) or adagrasib (ada) in previously treated locally advanced or metastatic KRAS G12C-mutated NSCLC. Given the evolution of KRAS G12Ci in this space, what is notable here is the direct prospective comparison to current KRAS G12Ci (adagrasib / sotorasib). Looking forward to ascertain magnitude of potential benefit and safety differences. 3⃣INTerpath-001: Phase 3 study of the mRNA-based individualized neoantigen therapy (INT) intismeran autogene (intismeran) plus pembrolizumab (pembro) vs pembro alone for adjuvant treatment of resected stage IIB-IV melanoma (MEL) Technically not a lung cancer study, but I believe this trial to be game-changing from a proof-of-concept approach. In my mind, this study establishes personalized mRNA-based approaches as a viable approach and worthy of research and clinical investment. @lcsmchat @OncoAlert @OncLive @Onco_Nexus @LungCancerEu @Lung_Cancers @LungCancerRx @MedwatchHQ @KRASKickers @SclcSMASHERS @YoungLungCancer
𝕏Twelve more patients in a hundred stay recurrence-free at 2 years — on top of pembrolizumab alone. INTerpath-001 (LBA1, #ESMO26): resected stage IIB–IV melanoma; intismeran autogene + pembrolizumab vs pembrolizumab (n=1,137). Early release after embargo breach — confirm at PS I (Long). @ProfGLongMIA
𝕏Enjoyed @MarcoGerlinger's take on INTerpath & the discontinued BNT-122 CRC study at #ESMO26. What can each teach us? A reminder: we’re testing a strategy: that includes tumour biology, combination therapy and patient selection and not just a vaccine. #ESMOAmbassadors https://t.co/NfRxtIrsui
𝕏Congratulations on bringing INTerpath-001 to PS I — a positive Phase 3 on an active control is a high bar. What I most want from Long’s slides: stage IIB vs III/IV subgroup RFS, timing of toxicity relative to immunization doses, and manufacturing turnaround / treatment-start delay in the personalized arm. Circulating: RFS HR 0.58, +12.2 pp at 24 mo; G≥3 23.6 vs 20.3. OS still the endpoint that decides clinic adoption.
𝕏#ESMO26 INTerpath-001 8 Grade 5 AEs in the experimental arm, 0 in the control arm. Of course, it could all be pure coincidence! After all, 6 of the 8 events were not considered TRAE Perhaps it was just the excitement of being randomized to the experimental arm? I'm genuinely curious about the independent causality assessment.
𝕏#ESMO26 | INTerpath-001: My Personal Perspective Ahead of the Presidential Session This innovation deserves recognition: a groundbreaking result for personalized cancer vaccines. However, in patients with macroscopic stage III melanoma who are eligible for neoadjuvant IO, this trial does not establish the added value over contemporary perioperative strategies. Neoadjuvant treatment can produce substantial responses while allowing some patients to avoid adjuvant therapy. The trial design I would prioritize is: Neoadjuvant IO → surgery → standard adjuvant therapy ± a personalized vaccine in patients without a major pathological response. Here, “failure to achieve a major pathological response” is a more appropriate selection criterion than “any residual disease.” Patients with minimal residual viable tumor who still achieve a major pathological response should not automatically receive additional treatment. This approach would direct treatment intensification toward patients at higher risk of recurrence. The key biological uncertainty, however, is that IO-resistant residual disease is not necessarily vaccine-sensitive. Whether vaccination can overcome that resistance needs to be demonstrated. This criticism should remain specific to that population: INTerpath-001 retains distinct clinical value for patients with stage IIB/IIC disease and those who underwent surgery without neoadjuvant therapy.
𝕏Superb presentation by Georgina Long! INTerpath-001: adding personalized mRNA vaccine intismeran to pembrolizumab reduced recurrence/death risk by 42% in resected stage IIB-IV melanoma (HR 0.58). A major step for cancer vaccines! #ESMO26 @OncoAlert @myESMO #ESMO26 https://t.co/9miRzK7fhb
𝕏I admit i am very much into intismeran…and it seems many others too as it is standing room only here… Fabulous presentation/data on the Interpath-001 trial demonstrating clear benefit of this space age bespoke neoantigen vaccine along w pembro for pts w resected high risk melanoma as to 40% or so improvement in RFS/distant met free survival Indeed a landmark trial for precision medicine and hopefully not too Long before we see confirmation in nsclc/other trials! Interpath- indeed makes us foresee a wonderful path and light ahead for our field! #ESMO26
𝕏🔥 #ESMO26 INTerpath-001, full data (now yes) On top of RFS HR 0.58 and DMFS HR 0.62: • Manufacturing success >99% • >90% of patients got the maximum 34 neoantigens 🔍 Practice-changing? For a population, yes. Two things still to prove: • Can an mRNA strategy rescue patients primary refractory to neoadjuvant ipi-nivo (no pathologic response)? • Will it move OS in stage II-IIIB too? Resuls in @NEJM soon @myESMO @OncoAlert @Larvol @_SEOM #Melanoma #Immunotherapy
𝕏👑 Presidential #ESMO26! INTerpath-001: personalized mRNA vaccination reaches phase III in melanoma. Resected stage IIB–IV melanoma, N=1,137: intismeran + pembrolizumab vs pembrolizumab. 💥 At 24 months: • RFS: 82.2% vs 70.0% → HR 0.58 • DMFS: 88.5% vs 80.2% → HR 0.62 • Absolute gains: +12.2% RFS / +8.3% DMFS • Benefit emerges mainly after 6 months • Grade ≥3 AEs: 23.6% vs 20.3% • OS still immature A clinically meaningful new mechanism, but the real question now is positioning 🤔 For macroscopic stage III: adjuvant personalized vaccine after surgery, or neoadjuvant ipi/nivo before it? Biomarkers may ultimately decide. Congrats to @ProfGLongMIA and all the team! 👏🏼 @OncoAlert @OncoReporte @myESMO @_SEOM @GrupoMelanoma
𝕏🔥 Personalized cancer vaccines delivering impressive results at #ESMO26! @ProfGLongMIA presents the phase III INTerpath-001 trial in resected high-risk melanoma. Individualized neoantigen mRNA vaccine intismeran autogene + pembrolizumab vs pembrolizumab alone. Key results: 🔹 DMFS: HR 0.62 (95% CI 0.45–0.85), p=0.002 🔹 24-month DMFS: 88.5% vs 80.2% 🔹 RFS: HR 0.58 (95% CI 0.45–0.75) A major milestone for personalized cancer vaccines! A promising step towards truly individualized immunotherapy. #ESMOAmbassador #ESMO26 #Melanoma #CancerVaccines #Immunotherapy
𝕏A long-awaited breakthrough in cancer vaccines. One patient. One tumor. One personalized mRNA vaccine. INTErpath-001 brings this vision closer to clinical reality. Are we ready to deliver it? @myESMO @OncoAlert @OpenMedicineHQ #ESMO26 @ProfGLongMIA @FAndreMD @curijoey @YJanjigianMD
𝕏🆙#ESMO26 Presidential Symposium I 🔥INTerpath-001: Phase 3 Study of the mRNA-Based Individualized Neoantigen Therapy (INT) Intismeran Autogene (Intismeran) Plus Pembrolizumab (Pembro) vs Pembro Alone for Adjuvant Treatment of Resected Stage IIB-IV Melanoma (MEL) 🎙️ @ProfGLongMIA 🔢LBA1 🎯Met Primary Endpoint: Significantly Improved RFS 🎯24-Mo 82.2% vs 70.0%, HR 0.58 🎯DMFS HR 0.62 🎯Grade≥3 AEs 23.6% vs 20.3% ☑️NCT05933577 🔗 https://t.co/Lb6tzuMm0z @OncoAlert @Larvol @myESMO
𝕏#ESMO26 | INTerpath-001👇 https://t.co/9zQwLrfkBe https://t.co/jA8OFWtQqd
𝕏A milestone for personalized cancer vaccines. INTErpath-001: 42% lower recurrence/death risk; 24-month RFS 82.2% vs 70%. Can we extend this benefit to other cancers? @myESMO @OncoAlert @OpenMedicineHQ #ESMO26 https://t.co/567xy0e42L
𝕏#ESMO26 Starting the Presidential Session with INTerpath-001 Intismeran + pembro shows ⬇️risk of recurrence and of distant mets including high-risk stages. A major step forward for personalised cancer vaccines, looking forward to see the data in other tumour types @OncoAlert https://t.co/SBGq9djNGK
𝕏Presidential symposium 1️⃣!! Interpath-001: adjuvant INT (intismeram) plus pembro impact in RFS & DMFS for stage II-IV resectable melanoma #ESMO26 @ProfGLongMIA @myESMO #personalizedmedicine https://t.co/G5Pf70eb1x
𝕏Practice-changing at #ESMO26 Presidential @ProfGLongMIA INTerpath-001: personalized mRNA neoantigen Tx (intismeran) + pembro vs pembro alone in resected stage IIB–IV melanoma (n=1,137) RFS HR 0.58, 2-yr RFS 82% vs 70% DMFS HR 0.62, 2-yr DMFS 89% vs 80% It's the 1st phase 3 win for an individualized cancer vaccine against an active IO control. OS is pending, but the adjuvant melanoma bar just moved. Kudos to the entire team! Moving moment as @ProfGLongMIA paid tribute to Dr. Jeff Weber, who designed this trial and enrolled patients until his passing. Jeff was a dear friend and my colleague at @MoffittNews and today's results are his legacy 💙 Bladder next: INTerpath-005 in MIUC, look forward to seeing the data in future!
𝕏with 1st neoantigen vaccine intismeran w pembro vs placebo w pembro, increased recurrent free & metastasis free survival in resected melanoma. Congrats to the teams!! @oncoalert @myESMO #ESMO26 https://t.co/2orLB7ug7y
𝕏INTerpath-001 - the result of decades of scientific advances and research led to this moment! And brilliant delivery by @ProfGLongMIA Personalized mRNA vaccines + Pembro as adjuvant trt improve RFS for pts with resects IIB-IV Melanoma!! Important points: Tox: a significant number of adverse events occurred BEFORE the vaccine was started Access: the vaccines was given globally #ESMO26 @OncoAlert
𝕏There is clear additive activity with a personalized mRNA vaccine with intismeran autogene with pembrolizumab in melanoma where dual PD1 failed before. Presented by @ProfGLongMIA - I hope the same will come in the future for RCC #ESMO26 #Oncoalert https://t.co/Owe1QY5Uuh
𝕏#ESMO26 @myESMO Presidential session presentation by session @ProfGLongMIA INTerpath-001: intismeran + pembro vs pembro in resected stage IIB–IV melanoma (n=1,137) RFS HR 0.58, 2-yr RFS 82% vs 70% DMFS HR 0.62, 2-yr DMFS 89% vs 80% 1st phase 3 win for an individualized cancer vaccine against an active IO control. OS is pending, but the adjuvant melanoma bar just moved! Moving moment as @ProfGLongMIA paid tribute to Dr. Jeff Weber, who designed this trial and enrolled patients until his passing. Jeff was a dear friend and my colleague at @MoffittNews and today's results are his legacy 💙 Bladder next: INTerpath-005 in MIUC, look forward to seeing the data in future!
𝕏#INTerpath001 amazing adjuvant melanoma trial of a personalized vaccine plus pembrolizumab. 17% of patients didn’t have sufficient tumor sample to create the neoantigen vaccine. DFS highly positive and OS immature. @oncoalert #ESMO26 excited to see other tumor data coming soon! https://t.co/VyUKabIWE2
𝕏First positive trial with individualized neoantigen therapy! Adding intismeran (personalized mRNA vaccine) to pembro improves RFS and DMFS in stage IIB/IIC, III, or IV resected melanoma Opening the door to this approach across different solid tumors! @OncoAlert #Esmo26 https://t.co/lcNNegQ5S0
𝕏#ESMO26 Interpath-01; 🚨addition of individual tumour directed mRNA vaccine intismeran n=1137 patient phIII trial in resected #melanoma to pembro anti-PD1. ⬇️ risk of distant mets or death by 38%. Similar G3-5 TRAEs similar ~14%. OS not mature. 💥A new era in personalised mRNA therapy?
𝕏Welcome INTERpath-001 first mRNA vaccine for melanoma treatment with no potentiation of Pembro AE https://t.co/ZKEYemE2k2
𝕏INTerpath-001 adjuvant Intismeran Autogene + Pembro vs Pembro for resected stage IIB-IV #Melanoma Impressive RFS and distant metastasis free survival improvement with a truly personalized and neoantigen-driven approach @ProfGLongMIA #ESMO26 @myESMO https://t.co/NQ1xb6krW8
𝕏Balanced discussion by prof Svane of the phase III INTerpath-001 trial at #ESMO26. Personalized cancer vaccines represent a major step forward, but: 🔹 Will the RFS benefit translate into improved OS? 🔹 Where should adjuvant vaccination fit alongside neoadjuvant ipilimumab/nivolumab? 🔹 Who benefits most? Predictive biomarkers remain urgently needed. 🔹 Manufacturing complexity, treatment delays, costs and access are major challenges. 👏 Compelling data and a milestone for personalized oncology, but clinical positioning and real-world feasibility will be crucial! #ESMOAmbassador #ESMO26 #Melanoma #CancerVaccin
𝕏In INTerpath-001, the combination of adjuvant Intismeran plus pembro is superior to pembro alone in resected melanoma mproves RFS in ITT 70% vs 82.2% HR 0.58 #ESMO2026 @darioT_ @myESMO @DrChoueiri @FAndreMD @OncoAlert https://t.co/lKvGZajEEZ
𝕏Georgina Long presented INTerpath-001 at #ESMO26: intismeran + pembrolizumab vs placebo + pembrolizumab as adjuvant therapy for resected melanoma. It met the primary RFS endpoint (42% reduction in risk of recurrence or death) and the key secondary DMFS endpoint (38% reduction). OS is still immature, and follow-up is ongoing.
𝕏🧬 Personalized mRNA vaccines work‼️ 📈 INTERPATH-001 met its primary endpoint in resected melanoma patients, paving the way to other tumor types and combinations, including lung 🫁 #cancer 🚀 🌓 One small step for a vaccine, one giant leap for personalized medicine. #ESMO26 @myesmo
𝕏When urologists are paying attention to Melanoma trials: exciting times for personalized cancer vaccines with the data from INTERPATH-001 excellently presented by @ProfGLongMIA at #ESMO2026! Curious for what’s to come in GU! https://t.co/DvwMBcBTMB
𝕏🔥 Presidential Symposium I #ESMO26 INTerpath-001: double-blind phase 3 study of intismeran (mRNA vaccine) + pembro as adjuvant therapy for resected stage IIB–IV #melanoma ✔️ RFS 82.2 vs 70% HR 0.58 ✔️ DMFS 88.5 vs 80.2% HR 0.62 ☣️ No increased risk of toxicity in the combination ✅🧫 mRNA Vaccine in adjuvant melanoma treatment together with anti-PD1 @OncoAlert @myESMO @ASCO @_SEOM @UTMDAnderson @brunolarvol 👇🏽👇🏽
𝕏#ESMO26 | LBA1 – INTerpath-001 ✅ First positive Phase 3 of individualized mRNA neoantigen therapy in adjuvant melanoma Intismeran autogene + pembrolizumab vs pembrolizumab alone (Resected stage IIB–IV | N=1,137 | median FU 24.6 mo) ✅ RFS: HR 0.58 (0.45–0.75) | p<0.001 → 24-mo RFS 82.2% vs 70.0% ✅ DMFS: HR 0.62 (0.45–0.85) | p=0.002 → 24-mo DMFS 88.5% vs 80.2% ✅ Benefit across most subgroups ✅ Manageable safety (no potentiation of pembro AEs) ✅ OS still immature New benchmark for adjuvant melanoma. Presented by Georgina V. Long #ESMO26 #Melanoma #mRNA #INTerpath001 @myESMO @OncoAlert
𝕏ESMO 2026 | Personalized mRNA Cancer Vaccines Deliver Phase III Success! INTerpath-001: Intismeran + pembrolizumab in resected high-risk melanoma. • RFS: HR 0.58 (42% risk reduction) • 24-month RFS: 82.2% vs 70.0% (+12.2%) • DMFS: HR 0.62 (38% risk reduction) 3 Key Takeaways: 1. Personalized neoantigen vaccines have demonstrated clinically meaningful Phase III efficacy. 2. No major increase in severe treatment-related toxicity, but overall survival data remain immature. 3. Predictive biomarkers, ctDNA/MRD, and optimal sequencing versus neoadjuvant immunotherapy are the next critical questions. A major milestone for personalized oncology. #ESMO26 @myesmo @oncodaily @OncoAlert #CancerVaccines #Melanoma
𝕏Phase 3 results from the INTerpath-001 trial confirm that the individualized mRNA vaccine plus pembrolizumab significantly improves outcomes in adjuvant treatment of malignant melanoma. The era of mRNA vaccines in oncology has officially begun!👏 #ESMO26! https://t.co/BO9n6VKQpp
𝕏Surgeon's view: they want different things from the operation. Neoadjuvant pembro treats the disease before it comes out. The vaccine is built from the tumour after it's out. INTerpath-001 enrolled patients with no prior systemic therapy, so it doesn't answer the "both" question.
𝕏One Patient. One Tumor. One mRNA Vaccine. 🧬💉 INTErpath-001: Cancer’s custom nightmare just arrived. Ready? 🚀
𝕏Merck and Moderna's personalised mRNA melanoma vaccine (intismeran) plus pembrolizumab cut recurrence or death by 42% vs pembrolizumab alone in INTerpath-001: 1,137 patients, completely resected stage IIB–IV. 2-year recurrence-free 82.2% vs 70.0%. Overall survival not mature yet. The detail surgeons should notice: each vaccine is built from that patient's own resected tumour, coding up to 34 neoantigens. So the operation is no longer just the end of the cancer pathway. It's the first step in making the drug. How we handle the specimen, whether there's enough tissue, how fast it reaches sequencing: all of that now sits inside the treatment.
𝕏Topline ESMO data from INTerpath-001 (#Moderna's personalized cancer vaccine) reportedly leaked elsewhere: RFS HR 0.58 (Honestly shame on people for breaking embargo’s). There is a huge divide here between physicians and non-physicians on the outcome. To me, this was huge and clearly worked. This hazard ratio puts it in the company of the most paradigm-changing adjuvant trials in oncology history. Yes, the same outcome can be generated from giving pembro in the neoadjuvant space [SWOG S1801 neoadjuvant + adjuvant pembro vs adjuvant pembro alone: EFS HR 0.58.] That isn't the point. A peptide vaccine strategy yielded the same outcome as having a tumor in vivo. This demonstrates the tech worked, now it can be applied more broadly or potentially even supercharge the neoadjuvant space with less immunogenic tumors. Time to do better and apply to more things (like colon cancer pls). #ESMO26 @OncoAlert @TheGutOncLab
𝕏🚨 #ESMO26 | Phase III INTerpath-001 🚨 After an early embargo breach, @myESMO brought the abstract release forward!!!!!! And yes, it’s clearly positive: 📉 RFS HR 0.58 📉 DMFS HR 0.62 But here’s the uncomfortable part: SWOG S1801 also reported an HR 0.58…simply by moving 3 doses of pembrolizumab BEFORE surgery… ☝🏼Not the same population. Not the same endpoint. Not a cross-trial comparison. Still, in 2026, should a personalized mRNA vaccine really be benchmarked against adjuvant pembro alone? Before calling this a new standard, I want to see the vaccine face the NEOADJUVANT era. Same HR. Different path. And that may be the real INTerpath question 👀 @OncoAlert @OncoReporte @myESMO @_SEOM @GrupoMelanoma What do you think? @SuyogCancer @OncBrothers @A_May_MD @Dr_R_Kurzrock
𝕏Some thoughts on the INTerpath-001 backlash, and the simplistic "neoadjuvant already does better, so why bother" take. I think it misses a few important things. ➡️ First, the neoadjuvant data (S1801, NADINA) come from patients with macroscopic, clinically detectable nodal disease. INTerpath-001 also includes node-negative IIB/IIC and patients whose nodal disease only showed up on sentinel node biopsy. In the big SLN trials, about two thirds of SLN+ patients had deposits ≤1 mm. None of these patients are neoadjuvant candidates. We see the same confusion in #NSCLC all the time, when people compare stage IIIA from adjuvant trials (pathological staging) with stage IIIA from neoadjuvant trials (clinical staging). Same stage on paper, not the same patients. ➡️ Second, INTerpath-001 was designed before NADINA read out, when adjuvant anti-PD-1 was still the default for resected stage III. Judging it against today's practice is a bit of hindsight. ➡️ Third, I suspect the most logical place for a neoantigen vaccine is after neoadjuvant ICI in patients who don't reach pCR. INTerpath-009 is already testing exactly this in NSCLC, so we'll get some hints there. ➡️ And all of this comes with only an absolute ~3% increase in grade ≥3 toxicity, which also belongs in the balance. For macroscopic stage III, the critique lands. I want to see the full data and the stage breakdown at LBA1. But I'd be careful firing at this result before we've even seen it properly. @OncoAlert @Larvol @KolPulseAI @_SEOM @myESMO #Melanoma #ESMO26
𝕏ADJUVANT MELANOMA | ESMO 2026 INTerpath-001: How Much Benefit Are We Actually Adding? Adding a personalised mRNA vaccine to pembrolizumab improved 2-year RFS from 70.0% to 82.2%. Absolute gain: +12.2 percentage points | HR 0.58 Unlike earlier adjuvant trials against placebo or ipilimumab, this benefit was demonstrated on top of pembrolizumab. ⚠️ Cross-trial comparisons are not valid: populations, comparators and follow-up differ. OS benefit remains unproven. The key question: Will this RFS advantage translate into improved long-term survival? #MVOnco #ESMO2026 #INTerpath001 #Melanoma #CancerVaccine #Immunotherapy
𝕏Cautionary note – personalized mRNA neoantigen vaccine (intismeran / mRNA-4157) in resected melanoma. The reported reduction in recurrence is real, yet several core uncertainties remain unresolved. The control was an inactive placebo, not a scrambled or irrelevant mRNA matched for mass and antigen number. Non-specific innate effects of the mRNA-LNP platform therefore cannot be separated from antigen-specific activity. No published in vitro data have tested whether the encoded neoantigen peptides or mRNA constructs exert any direct stimulatory or pro-proliferative effect on melanoma cells independent of the immune system. This possibility has not been experimentally excluded. Overall survival benefit is still immature, and the contribution of the vaccine outside the adjuvant Keytruda combination is unproven. Manufacturing time, cost, and scalability constraints are substantial; generalizability beyond highly selected resected melanoma remains limited. These open questions do not erase the clinical signal. They do limit how confidently the mechanism and the true incremental value of the personalized neoantigens can be asserted.
𝕏🚨 Scientific embargoes exist for a reason: fair access to data, scientific integrity and, ultimately, patients. Seeing a major #ESMO26 study disclosed ahead of schedule is disappointing. I think ESMO takes its embargo policy seriously, and I would expect a breach of this magnitude to have consequences. Science should set the timeline, not the stock market 😡 With INTerpath-001, someone clearly took a shortcut on the path to the data. @OncoAlert @OncoReporte @myESMO @_SEOM @GrupoMelanoma
𝕏I note of skepticism that the the adjuvant individualized neoantigen therapy data is not meaningful progress In case of NSCLC- we shall learn as there are 3 separate studies ongoing (one just completing accrual!) But scientifically… Neoadj IO works better compared to adj IO as activated T cells need to see the “in situ vaccine” of the native tumor for long-standing benefit. Postop in micromet setting simply stated there is just no cancer cells to work with- as an analogy, for T cells to build muscles they need machines in the gym… otherwise, no lifting- no muscle… Now the beauty of INT is that it does provide an excellent gym with the best tailored neoantigen weight machines for the immune system to work with! So w results of Interpath-001 i’d say- T cells and all of us, lets go to the gym and Cheers on a first set of great results!
𝕏💉لقاح mRNA شخصي يقلل خطر عودة سرطان الجلد أو الوفاة بنسبة 42% 📉 أعلنت شركتا Moderna و Merck نتائج تجربة INTerpath-001 من المرحلة الثالثة 📉 اختبرت التجربة لقاح Intismeran autogene المصمم خصيصاً وفق الطفرات الجينية لورم كل مريض بشكل شخصي بالإضافة إلى العلاج المناعي Pembrolizumab بعد الاستئصال الجراحي لسرطان الجلد الميلانيني عالي الخطورة 📉 شملت التجربة أكثر من 1,100 مريض 📉 النتيجة 🔹انخفاض الخطر النسبي Relative Hazard Reduction لعودة السرطان أو الوفاة 42% 🔹انخفاض الخطر النسبي للانتشار البعيد أو الوفاة 38% 🔹البقاء دون عودة السرطان مع العلاج المركب 82.2% و تمثل نسبة المرضى الذين بقوا دون عودة السرطان أو الوفاة خلال عامين Recurrence-Free Survival 🔹البقاء دون عودة السرطان مع Pembrolizumab وحده 70% 📉 الأهمية السريرية: يمثل هذا أول دليل من المرحلة الثالثة على فائدة سريرية للقاح سرطاني شخصي قائم على تقنية mRNA عند إضافته إلى العلاج المناعي ❗️النتائج مشجعة انخفاض الخطر النسبي بنسبة 42% لا يعني انخفاض الوفيات وحدها بهذه النسبة بيانات البقاء الكلي غير مكتملة و لم يحصل اللقاح بعد على الموافقات التنظيمية https://t.co/Znw4S3Pl7Z https://t.co/wGMx1VeKui https://t.co/FXD240UPQd
𝕏with med onc pearls for neoantigen mRNA vaccines. The future is happening now — esp w readout of INTERPATH-001 trial this #ESMO26 @myESMO @oncoalert https://t.co/EhNz2A40yG
𝕏#Madrid #ESMO26 | Main findings from INTerpath-001 released: #Intismeran + #pembrolizumab reduced risk of recurrence or death by 42% (HR, 0.58), risk of distant metastasis or death by 38% (HR, 0.62); 24-monRFS rates 82.2% vs 70.0% | Proud to be part of this effort @MoffittNews
𝕏Encouraging developments in personalised cancer immunotherapy. Phase 3 results from the INTerpath-001 trial suggest that an investigational mRNA-based treatment, intismeran autogene, combined with pembrolizumab, reduced the relative risk of melanoma recurrence or death by 42% compared with pembrolizumab alone. At two years, 82.2% of patients receiving the combination remained free from recurrence, compared with 70% in the control group. The treatment is individually designed using mutations identified in each patient's tumour. Overall survival outcomes remain under evaluation, but these findings represent promising progress towards more personalised approaches to cancer treatment. #Melanoma #CancerResearch #mRNA #Immunotherapy #PrecisionMedicine https://t.co/7gPUjc3Bjh
𝕏When INTerpath-001 opened, neoadjuvant pembro had only one randomized phase 2 behind it. The phase 3 evidence came later with NADINA. Adjuvant pembro was a justified control arm. Evidence often moves faster than trials, that's everyday oncology. But I insist, it only applies to macroscopic disease, not to IIB-IIC or cN0 stage III.
𝕏ツチノコ的ESMOレビュー① いきなり情報解禁前にデータが漏れるという大波乱の幕開けです。 モデルナの株価が25%下落の 大・暴・落！！ 個別化mRNAがんワクチン 「intismeran autogene」 の第Ⅲ相試験、INTerpath-001ですね。 すでにデータが世に出てしまったため、ESMOが正式に情報解禁を前倒ししました。 これ、何をやっているかというと、、 患者さんのがんの遺伝子情報を調べて、その人のがんに特有の目印を狙うmRNAワクチンを作る。 それを使って、免疫に 「この目印のあるがん細胞を攻撃してくれ」 と教える治療です。 患者さんごとに作る、オーダーメイドのがんワクチンですね。 今回の対象は完全切除後のStage IIB〜IVの悪性黒色腫の患者さん1,137人。 ①個別化mRNAがんワクチン＋キイトルーダ（Pembrolizumab） ②キイトルーダ単独 を比較しています。 結果は、、 【2年無再発生存率】 82.2％ vs 70.0％ HR 0.58、p＜0.001 再発または死亡のリスクが42％低下。 【2年遠隔転移無生存率】 88.5％ vs 80.2％ HR 0.62、p＝0.002 遠隔転移または死亡のリスクが38％低下。 Grade 3〜5の治療関連有害事象は 14.2％ vs 13.4％でした。 全生存期間はまだ追跡が必要ですが、キイトルーダに上乗せして再発を減らしたというのは、臨床的には重要な結果だと思います。 ところが、、 モデルナの株価は、データ公開後に25％超下落したと報じられています。 「え、効いてるのに何で？」 ってなりますよね。 そもそもモデルナ株は、今回の治療への期待などから年初来500％超も上昇していました。 なので、良い結果が出ること自体は、すでに株価に織り込まれていたという話です。 加えて、先行する第Ⅱ相試験から期待されていたほどには 遠隔転移を抑える効果が大きくなかった、という受け止めもあったようです。 ただし、対象や追跡期間の違う試験をそのまま比較して「効果が落ちた」とは言えません。 個人的には、患者さんごとに作るmRNAがんワクチンが、第Ⅲ相で再発抑制効果を示したこと自体が大きいと思います。 ただ、これで色々ながんに効くと決まったわけではありません。 まずはメラノーマでの結果として評価して、OSと他のがん種の試験の結果を今後は見ていきたいですね。 ツチノコ的には数十年もすればゲノム含めがん治療は完全に個別化される可能性があると思っているので 標準治療の教育体系から変えていかなくてはならないのでは？ という印象です。 公式資料： https://t.co/NWcEXu7k0B #ESMO26 米モデルナの株価が一時26%安 治験データ漏洩、期待に届かず：日本経済新聞 https://t.co/ZM4mZ3zM9N
𝕏‼️ Interesting commentary on INTerpath-001 No need for vaccine if pembro given neoadjuvant? Wow, await further details / data here, but what a dud! Precision/Personalized dud https://t.co/i1SNiVUjfz
𝕏How to improve outcomes in patients with metastatic melanoma post-surgical resection, and specifically, vs controls: —Reduce 2-year mortality from 82 to 70% —Reduce recurrence by 42% Treat with a personalized mRNA neoantigen vaccine @statnews @adamfeuerstein
𝕏🚨 #ESMO26 INTerpath-001 leaked before the embargo, so @myESMO released it early ➡️ Intismeran (mRNA-4157) + pembro vs placebo + pembro, adjuvant stage IIB-IV #melanoma • 24-mo RFS 82.2% vs 70.0% | HR 0.58 • 24-mo DMFS 88.5% vs 80.2% | HR 0.62 • G≥3 AEs 23.6% vs 20.3% 👇👇
𝕏Topline ESMO data from INTerpath-001 (#Moderna’s personalized cancer vaccine) reportedly leaked elsewhere: DFS HR 0.58 This hazard ratio puts it in the company of the most paradigm-changing adjuvant trials in oncology history:
𝕏@moderna_tx will ultimately find its strength in solid tumors including melanoma that have poor response to neoadjuvant as adjuvant combo including #nsclc - don't forget that there are many stage 3 patients that aren't offered neoadjuvant. Also a broader group of III melanoma based on sentinel node - benefit for a broader group. The head to head comparison is false.
𝕏🚨 ESMO 2026 | INTErpath-001 (LBA1) - as data is released by Esmo 🔹 24-month RFS: 82.2% vs 70.0% HR 0.58 (95% CI 0.45–0.75); P<0.001 🔹 24-month DMFS: 88.5% vs 80.2% HR 0.62 (95% CI 0.45–0.85); P=0.002 🔹 Grade ≥3 adverse events: 23.6% vs 20.3% The trial randomized 1,137 patients with resected stage IIB–IV melanoma. Both arms received pembrolizumab; the experimental arm added an individualized mRNA neoantigen therapy. The key question now: will better recurrence control translate into an overall survival benefit? Looking forward to full dataset on day 2 . #ESMO26 @myESMO
𝕏🤷🏽♀️Proof that the market is irrational. This now officially released Merck/Moderna cancer vaccine (mRNA-457) results from a Phase 3 study of 1,100 pts w high-risk melanoma to be presented at #ESMO26 look impressive to me- cuts melanoma death or recurrence risk by 42% and cancer metastases by 38% but shares fall ?
𝕏An embargo breach at a congress as prestigious as ESMO is unacceptable. If I remember correctly, something similar happened in 2023. It is deeply troubling to feel that sharing scientific data is driven more by stock market movements than by patients and science…!!!
𝕏@OncoAlert @brunolarvol @adamfeuerstein An alleged third-party leak of the top plenary presentation of the #interpath-001 at #ESMO2026 . Source still unknown. #Intismeran autogene + pembro reportedly reduced recurrence or death (EFS) risk by 42% (HR 0.58) for resected IIB-IV #melanoma Possible #PracticeChanging pending safety and full text publication
𝕏Looking forward to the presentation and discussion. #LBA1 Phase 3 INTerpath-001 trial results at #ESMO26 👉🏽The Kaplan-Meir curves don’t always tell the whole story. Side effects, cost, access matter but 👉🏽Its is very exciting that a personalized mRNA technology can be used to control cancer recurrence.
𝕏Personalised mRNA therapy reaches Phase 3 in melanoma: INTerpath-001 met RFS and DMFS with intismeran autogene + pembrolizumab. The key question now is magnitude-HRs, absolute benefit and detailed toxicity are still awaited. Presented by @ProfGLongMIA at @myESMO. Developed by @moderna_tx + @Merck. #ESMO26 #Melanoma
𝕏I’d applaud these trials, but I’d remain seated 😅😅 INTerpath-001 is an innovative treatment approach. However, there is no comparison with neoadjuvant nivo + ipi, a strong option particularly in macroscopic stage III melanoma. DeLLphi-305 showed a survival benefit with maintenance tarlatamab + durvalumab. But the comparator is durvalumab monotherapy. We also have positive results from IMforte with maintenance atezo + lurbinectedin. So this is another potential maintenance option; its place among the existing options remains to be defined. In HARMONi-GI1, even if not one but three trucks could fit between the Kaplan–Meier curves, global validation will still be expected because the trial was conducted exclusively in China 🫣 For me, VOLGA’s most interesting feature is the omission of adjuvant EV. As for the survival benefit of perioperative EV + immunotherapy, we already have strong data.
𝕏🧬 HOW DOES A PERSONALIZED mRNA CANCER VACCINE ACTUALLY WORK? As an oncologist, and also as a university professor, I strongly believe that understanding how a new treatment works is often the best way to understand why it may eventually change our clinical practice. So, what exactly is a personalized mRNA cancer vaccine? The concept is both sophisticated and surprisingly intuitive. 1️⃣ Start with the patient's own tumor 🧬 Every cancer is genetically different. By sequencing tumor DNA and RNA, and comparing this information with normal tissue , we can identify tumor-specific mutations. Some of these mutations generate abnormal proteins that are not present in healthy cells. These are called neoantigens. And importantly, they can become molecular "flags" allowing the immune system to distinguish cancer cells from normal cells. 2️⃣ Select the best targets 🎯 Not every mutation will generate an effective immune response. Bioinformatic algorithms therefore analyze the patient's tumor and predict which neoantigens are most likely to be recognized by their immune system. In the case of intismeran autogene, up to 34 patient-specific neoantigens can be selected. 3️⃣ Build an individualized mRNA therapy 💉 Here comes the fascinating part. A synthetic mRNA sequence encoding those selected neoantigens is manufactured specifically for that individual patient. Think about what this means. We are no longer simply choosing the best available drug for a patient. We are manufacturing a treatment based on the molecular identity of that patient's own cancer. 4️⃣ Teach the immune system what to recognize 🛡️ After administration, the mRNA enters cells and provides the instructions to produce the selected neoantigens. These neoantigens are processed and presented to the immune system, activating tumor-specific CD4+ and CD8+ T cells. The objective is to generate an immune response capable of recognizing cells carrying those same neoantigens. 5️⃣ Let T cells search for the cancer 🔎 Those activated T cells can then recognize tumor cells displaying the corresponding antigens and potentially destroy them. This is why combining personalized vaccination with PD-1 blockade such as pembrolizumab makes so much biological sense: 🎯 The vaccine may teach the immune system WHAT to attack. 🔓 Checkpoint inhibition may help the immune system KEEP attacking it. And this is where, in my view, the concept becomes much bigger than one drug or one tumor type. For many years, we have defined precision oncology as: “the right treatment for the right patient.” Personalized mRNA vaccines introduce an even more ambitious paradigm: “a treatment designed and manufactured specifically from the molecular characteristics of one patient's cancer.” @OncoAlert @_SEOM @moderna_tx @GEPAC_ Figure adapted from: doi:10.3390/cancers17091408.
𝕏Don’t miss the data at #ESMO2026 https://t.co/vFiJ0ruccU [QUOTED] JUST IN and via @Merck + @moderna_tx: A landmark moment for cancer immunotherapy. 🎯 Phase 3 INTerpath-001 is positive: the individualized mRNA neoantigen therapy intismeran (V940/mRNA-4157) + pembrolizumab significantly improved both RFS/DMFS vs pembrolizumab alone after resection of high-risk melanoma. For years, the idea of designing a treatment around the unique mutations of each patient’s tumor seemed aspirational. Now we have the first positive Phase 3 trial (N=1137) of an individualized neoantigen therapy—and of an mRNA-based cancer therapy. Personalized cancer vaccines are moving from promise to reality. Now we need to see the magnitude of benefit, durability, and ultimately OS. But today is an important day for the field—and hopefully for our patients. 👏 Congrats to #CathyWu @DanaFarber for her trailblazing research that is materializing in tangible outcomes! At @DanaFarber_GU we are closely working with Cathy + @DFCI_NeoVax team on several GU protocols, after our @Nature work with @BraunMDPhD et al (https://t.co/BdbKJqMKOw) https://t.co/Akd0XQt3ml
𝕏💉 Personalized mRNA cancer vaccines like intismeran autogene (V940/mRNA-4157) can work in genitourinary cancers? Three ongoing studies are particularly interesting. 🔵 KIDNEY CANCER — INTerpath-004 This randomized, double-blind Phase II study is evaluating adjuvant: V940 + pembrolizumab vs placebo + pembrolizumab following nephrectomy in patients with RCC at increased risk of recurrence. The primary endpoint is disease-free survival, with distant metastasis-free survival and overall survival among the secondary endpoints. If individualized neoantigen vaccination works in RCC, it could therefore tell us something very important about the biology of this platform: its potential may extend beyond simply selecting tumors with very high mutational burden. 🟠 MUSCLE-INVASIVE BLADDER CANCER — INTerpath-005 Here the development strategy is even more ambitious. INTerpath-005 is a Phase I/II program exploring V940 in two different settings. One cohort evaluates a perioperative strategy combining: V940 + pembrolizumab + enfortumab vedotin in cisplatin-ineligible patients undergoing radical cystectomy. Another randomized cohort evaluates adjuvant: V940 + pembrolizumab vs placebo + pembrolizumab in patients with high-risk resected muscle-invasive urothelial carcinoma. Could we combine three completely different therapeutic principles? 💥 EV → rapidly kills Nectin-4-expressing tumor cells 🔓 Pembrolizumab → releases PD-1-mediated immune inhibition 🎯 V940 → potentially generates an individualized T-cell response against that patient's unique tumor neoantigens ADC + checkpoint inhibition + personalized vaccination. Three mechanisms. One objective: eradicate micrometastatic residual disease before it can become clinically visible. And there is another bladder cancer study that should not be overlooked. 🟡 NON-MUSCLE-INVASIVE BLADDER CANCER — INTerpath-011 This ongoing randomized Phase II study is evaluating: V940 + BCG vs BCG alone in treatment-naïve high-risk NMIBC. I find this particularly intriguing. BCG has successfully exploited the immune system against bladder cancer for decades. Combining this established local immunotherapy with a systemic, individualized neoantigen-directed immune strategy represents a completely different way of thinking about treatment intensification in early bladder cancer. Of course, none of these studies is guaranteed to reproduce what we have seen in melanoma. For someone who has spent much of his career developing new treatments for kidney and bladder cancer, I find the possibility particularly exciting. Precision oncology has traditionally meant finding the right drug for the right patient. Personalized mRNA vaccines introduce an even more ambitious concept: creating a different drug for each individual patient's cancer. @OncoAlert @_SEOM @GuardConsortium @urotoday @GUOncologyNow @LACOG_group @GEPAC_
𝕏The mRNA vaccine success vs melanoma in a Phase definitive 3 randomized trial today is on top of signs of success for personalized mRNA neoantigen vaccines vs pancreatic cancer, triple negative breast cancer, and non-small cell lung cancer https://t.co/cv4iXW11mw
𝕏Positive phase 3 data for adjuvant pembro +/- personalized mRNA-based neoantigen vaccine for melanoma just announced by Merck and Moderna. Welcome to the future! https://t.co/rlKAvv7sbo https://t.co/BxYKh4NKKw
𝕏Newly minted twins- Intismeran and pembro are feeling pretty good today https://t.co/62jEnUt1mk https://t.co/5F8aw2rFqf [QUOTED] Are you into Intismeran- the new “individualized neoantigen therapy” (graciously avoiding the term “vaccine”) from Merck/Moderna? If you haven’t- you should! Maybe biggest news in onc for some time along w daraxonrasib- positive results in pivotal melanoma trial as to RFS improvement of this Space age technology which still makes my head spin- whole genome seq- neoantigen selection- personalized “INT” delivered to your patient in just a few weeks… and it works! Many studies ongoing in lung/bladder etc- eager to learn results (and continue to offer to our pts at Monte @BrendonStilesMD !) Now Back to the Future and let’s keep enrolling!
𝕏JUST IN and via @Merck + @moderna_tx: A landmark moment for cancer immunotherapy. 🎯 Phase 3 INTerpath-001 is positive: the individualized mRNA neoantigen therapy intismeran (V940/mRNA-4157) + pembrolizumab significantly improved both RFS/DMFS vs pembrolizumab alone after resection of high-risk melanoma. For years, the idea of designing a treatment around the unique mutations of each patient’s tumor seemed aspirational. Now we have the first positive Phase 3 trial (N=1137) of an individualized neoantigen therapy—and of an mRNA-based cancer therapy. Personalized cancer vaccines are moving from promise to reality. Now we need to see the magnitude of benefit, durability, and ultimately OS. But today is an important day for the field—and hopefully for our patients. 👏 Congrats to #CathyWu @DanaFarber for her trailblazing research that is materializing in tangible outcomes! At @DanaFarber_GU we are closely working with Cathy + @DFCI_NeoVax team on several GU protocols, after our @Nature work with @BraunMDPhD et al (https://t.co/BdbKJqMKOw) https://t.co/Akd0XQt3ml
𝕏🔥INTerpath-002: Adj Pembrolizumab + V940 (mRNA-4157) vs. Pembro 🆙 @Merck @moderna_tx 🎯Primary completion: 2030-06-25 👥Patients: Completely resected (R0) Stage II, IIIA or IIIB (N2) NSCLC, post-surgery and adjuvant chemotherapy 3⃣Phase III ⚖️Intismeran autogene (mRNA-4157) + pembrolizumab ⚖️Pembrolizumab alone (+ placebo) 🔢NCT06077760 #LCSM @OncoAlert @Larvol
𝕏A milestone for individualised neoantigen therapy and encouraging for the broader V940 (mRNA-4157) programme! Will the melanoma signal translate to GU cancers? - INTerpath-004: V940 + pembro vs pembro in adjuvant RCC - INTerpath-005: V940 + pembro vs pembro in MIUC @OncoAlert https://t.co/Q16XNfFHJX https://t.co/leaRqALAaQ
𝕏mRNA-4157-P201/KEYNOTE-942: Pembrolizumab +/- mRNA-4157 (V940, personalized cancer vaccine) as adjuvant therapy in resectable melanoma, a randomized phase 2, open-label study by Dr. Jeffrey Weber. What happens in melanoma will happen in lung cancer. #AACR23 #LCSM https://t.co/Rebrpl0Ltb
Note: per the ESMO 2026 LBA1 abstract, 82.2% vs 70.0% are 24-month recurrence-free survival rates (intismeran + pembrolizumab vs placebo + pembrolizumab), not mortality rates.
INTerpath-001 Key Takeaways
Results — ESMO 2026 LBA1 (presented Oct 24, 2026)
ITT, N=1,137 (757 vs 380); DCO 30-Jun-2026, median follow-up 24.6 mo. RFS (primary): 136 (18.0%) vs 111 (29.2%) events; HR 0.58 (95% CI 0.45–0.75), two-sided P<0.001 (multiplicity-adjusted significance level 0.024692); 24-month RFS 82.2% (79.3–84.8) vs 70.0% (65.0–74.5). DMFS (key secondary): 89 (11.8%) vs 71 (18.7%) events; HR 0.62 (0.45–0.85), two-sided P=0.002 (significance level 0.01608); 24-month DMFS 88.5% (86.0–90.6) vs 80.2% (75.6–84.0). Overall survival (secondary): immature and did not meet the prespecified significance boundary — HR 0.77 (0.45–1.31), two-sided P=0.33; follow-up is ongoing. RFS sensitivity analyses: piecewise HR 0.99 (0.66–1.49) for months 0–6 and 0.42 (0.30–0.58) after month 6 (ITT); mITT (patients who received intismeran or placebo as assigned, 726 vs 365) HR 0.51 (0.39–0.67), 24-month RFS 84.2% vs 70.4%. Topline (Aug 19, 2026): met the primary endpoint (RFS) and the key secondary endpoint (DMFS) — per the PR, the “first and only combination regimen” to do so in this adjuvant melanoma population; effect sizes were not announced at topline.
RFS HR 0.58 · DMFS HR 0.62 · OS immature (HR 0.77, P=0.33)
Source: ESMO 2026 LBA1 RFS/DMFS slides (Long) · LBA1 piecewise + summary slides (OS footnote) · LBA1 mITT slide · Merck/Moderna topline PR
Presented: ESMO 2026 Presidential Symposium (LBA1, Oct 24, 2026)
Moderna announced three intismeran autogene abstracts at ESMO Congress 2026 (October 23–27, Madrid). The INTerpath-001 Phase 3 full results were presented in the Presidential Symposium as LBA1 on October 24, 2026 by Professor Georgina V. Long (invited discussant: Inge Marie Svane). ESMO had released the abstract on October 22 after the embargo was breached; its figures are in the collapsed October 22 abstract-release panel near the bottom of this page, and the presented slides are in the Slides section. Moderna PR, Sept 21, 2026
Safety
As-treated population 755 vs 380 (DCO 30-Jun-2026, median follow-up 24.6 mo). All-cause grade 3–5 AEs 23.6% vs 20.3%; treatment-related grade 3–5 AEs 14.2% vs 13.4%; all-cause serious AEs 17.6% vs 15.8% (treatment-related 9.8% vs 11.1%). All-cause AEs led to discontinuation of any drug in 16.6% vs 9.5% (treatment-related 14.0% vs 8.7%); all-cause discontinuation of both drugs simultaneously 6.5% vs 5.3%. All-cause AEs led to death in 8 (1.1%) vs 0 patients, none related to intismeran; treatment-related AEs leading to death 2 (0.3%) vs 0. The presenter concluded that safety was generally consistent with previous experience, with no potentiation of pembrolizumab-associated AEs. Source: ESMO 2026 LBA1 adverse event summary slide (Long) · LBA1 summary slide
The KEYNOTE-942 antecedent — where today’s circulating numbers come from
The randomized Phase 2b KEYNOTE-942 (n=157, resected stage III/IV) first showed the benefit, consistent across every analysis (per Dr. Carlino’s ASCO 2026 slide, transcribed on this page): primary (Nov 14, 2022 cut) RFS HR 0.561 (95% CI 0.309–1.017, P=0.0266); 3-year (Nov 3, 2023) HR 0.510 (0.288–0.906); 5-year (Dec 15, 2025) HR 0.510 (0.294–0.887) — plus 5-year DMFS HR 0.411 (0.200–0.843, per the topline PR). ⚠ Hazard ratios circulating on announcement day are these Phase 2b figures — INTerpath-001’s own figures come from its LBA1 abstract (RFS HR 0.58, 95% CI 0.45–0.75) (ESMO 2026 LBA1 abstract, DCO 30-Jun-2026, median f/u 24.6 mo). Merck: KEYNOTE-942 5-year data
Regulatory status & clinical implications
⚠ Investigational — not approved by FDA or any other regulator. Merck and Moderna plan to engage regulators on filing submissions for intismeran + pembrolizumab based on these results. If the presented magnitude holds up, adjuvant melanoma would gain its first individualized therapy on top of PD-1 blockade — and the INT modality gains randomized Phase 3 validation with read-through to the sibling INTerpath programs (NSCLC, bladder, 1L melanoma). Physicians on this page flag the open questions: magnitude of benefit, durability, OS, manufacturing turnaround and cost. Merck topline PR
![INTerpath-001 ESMO 2026 slide: RFS and DMFS prespecified subgroup forest plots (Long, ESMO 2026) [too blurry] (3 of 3) (shared by Yago Garitaonaindía)](https://pbs.twimg.com/media/HVZ1fadXQAAQEkh.jpg?format=jpg&name=medium)
