Physician discussion, October 23–25

Physician posts on X, October 23–25.

INTerpath-001: intismeran autogene plus adjuvant pembrolizumab

Phase 3, N=1,137 (757 vs 380), resected stage IIB–IV melanoma: intismeran autogene (V940/mRNA-4157, Moderna and Merck), an individualized mRNA neoantigen therapy, plus pembrolizumab vs placebo plus pembrolizumab. RFS HR 0.58 (95% CI 0.45–0.75), two-sided P<0.001; 24-month RFS 82.2% vs 70.0%. DMFS HR 0.62 (0.45–0.85); 24-month DMFS 88.5% vs 80.2%. OS is immature and did not meet its prespecified significance boundary: HR 0.77 (0.45–1.31), P=0.33. (ESMO 2026 LBA1, Georgina V. Long; data cutoff Jun 30, 2026; median follow-up 24.6 months) In a prespecified sensitivity analysis, the RFS HR was 0.99 (0.66–1.49) for months 0–6 and 0.42 (0.30–0.58) after month 6. (LBA1 piecewise HR slide) All-cause grade 3–5 AEs 23.6% vs 20.3%; treatment-related grade 3–5 AEs 14.2% vs 13.4%. All-cause AEs led to death in 8 (1.1%) vs 0 patients; 2 (0.3%) vs 0 were treatment-related, none related to intismeran. (LBA1 AE summary slide) Intismeran is investigational and not approved by the FDA or any other regulator. Merck and Moderna plan to engage regulators on filings. (KOL Pulse INTerpath-001 page)

Physicians agreed the trial was positive. The debate was the comparator (adjuvant pembrolizumab, when SWOG S1801 and NADINA moved immunotherapy before surgery for macroscopic stage III), the deaths in the experimental arm, OS, and access. The presenter’s post comes first, then the discussant’s points as reported from the room.

Presenter and discussant

Professor Georgina Long AO (Bluesky @gvlongphdmd) @ProfGLongMIA

medical oncologist, Melanoma Institute Australia; INTerpath-001 presenter · Oct 25

It was a great honour to present the results of the phase 3 INTerpath-001 clinical trial at the #ESMO26 Congress in Madrid. This international trial included 1137 patients, across 157 sites, whose melanoma had been surgically removed, but who were at very high risk of it returning. The trial showed adding #intismeran autogene, an mRNA based individualised neoantigen therapy, to pembrolizumab reduced the risk of recurrence or death by 42%. This is the first phase 3 study to show that a treatment built from the unique ‘fingerprint’ of a patient’s own tumour can reduce the risk of recurrence or death from cancer. That fingerprint is read by sequencing the tumour, then a ‘wanted poster’ of the cancer is made as mRNA, showing the immune system exactly what to look for and attack. Having succeeded in melanoma, this proof of concept could mark the beginning of a foundational shift in how we treat cancer. Read more >https://t.co/quxTAFfntb A huge thank you to all patients and teams involved. @myESMO @Sydney_Uni @syd_health @Science_Academy @AAHMS_health @FulbrightAUS @NthSydHealth @ausoftheyear

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Alfredo Addeo MD @Alfdoc2

medical oncologist, Geneva University Hospitals · Oct 24

Balanced 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

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Day 3: NADINA at three years and new options after anti-PD-1

Both readouts below came from the melanoma rapid oral session on October 25.

NADINA: neoadjuvant ipilimumab plus nivolumab vs adjuvant nivolumab, 3-year update

Phase 3 trial (NCT04949113) in resectable macroscopic stage III cutaneous melanoma: neoadjuvant ipilimumab plus nivolumab, then surgery with response-driven adjuvant therapy, vs surgery followed by adjuvant nivolumab. The 3-year update was presented by Sonja Witteveen (2076RO). (ESMO 2026 program) Three-year EFS was 72.9% vs 50.0%, HR 0.42 (95% CI 0.31–0.59), p<0.0001. (ESMO 2026 2076RO, Sonja J. Witteveen; data cutoff Mar 30, 2026; median follow-up 36 months; KOL Pulse NADINA page) Nivolumab is FDA approved as adjuvant therapy for completely resected stage IIB–IV melanoma, and nivolumab plus ipilimumab for unresectable or metastatic melanoma; neoadjuvant use is not an FDA-labeled indication. (FDA labels for Opdivo and Yervoy) Physicians read the update next to INTerpath-001 and asked whether patients with a near-pathologic complete response still need adjuvant therapy.

After anti-PD-1: PLUG-IN GEM 2301, HERTHENA-PanTumor01 and FS222

Three rapid orals tested new options in melanoma that progressed on anti-PD-1 therapy: enfortumab vedotin plus pembrolizumab in PLUG-IN GEM 2301 (Guillermo de Velasco, 2074RO), patritumab deruxtecan (HER3-DXd) in the melanoma cohort of HERTHENA-PanTumor01 (Meredith McKean, 2073RO), and the CD137/PD-L1 bispecific antibody FS222 (Muhammad A. Khattak, 2075RO). Session chair Teresa M. Amaral led the discussion. (ESMO 2026 program) Enfortumab vedotin is FDA approved in urothelial cancer; all three treatments are investigational in melanoma. In the room, physicians noted similar response signals across three different approaches and called for better patient selection, biomarkers and inclusion of acral and mucosal melanoma.

Discussion first, then the presenting team

Mario Balsa @MarioBalsaMD

medical oncologist, melanoma, Hospital Clínic Barcelona · Oct 25

👑 Brilliant discussion by @TeresaSAmaral (the BEST!!!!!!) at #ESMO26 on the evolving post–PD-1 melanoma landscape. Three very different strategies, remarkably similar signals: ▪️EV + pembro: ORR 32% ▪️HER3-DXd: ORR 21% ▪️FS222: ORR 36% But the real message: ORR 30% is no longer enough! We need smarter trial populations, earlier referral, meaningful biomarkers and better representation of acral/mucosal melanoma. @OncoAlert @OncoReporte @myESMO @_SEOM @GrupoMelanoma

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Pablo A. Ballesteros @pabloteros

medical oncologist, Hospital 12 de Octubre, Madrid (PLUG-IN presenting center) · Oct 25

A special moment for our team: PLUG-IN trial presented by @g_develasco at #ESMO26! 🇪🇸 EV + pembrolizumab: 25% ORR in PD-1 refractory melanoma (33.3% acral). Nectin-4: higher cytoplasmic expression; no link to response. Next: transcriptomics to explore the biology. Stay tuned! https://t.co/5J7plOnbgw

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Mario Balsa @MarioBalsaMD

medical oncologist, melanoma, Hospital Clínic Barcelona · Oct 25

🔥 #ESMO26 | FS222 in PD-1–resistant melanoma! A tetravalent CD137/PD-L1 bispecific with encouraging activity in a difficult setting! 👥 N=42 💥 ORR 36% | mDOR 5.5 mo | mPFS 3.7 mo ▪️ 8/15 responders had primary resistance to prior IO ▪️ >10× ↑ CD8+ T-cell proliferation & IFNγ Safety was manageable, although G≥3 TRAEs occurred in 45.2%…mainly immune-mediated hepatic/hematologic events @OncoAlert @OncoReporte @myESMO @_SEOM @GrupoMelanoma

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Other melanoma readouts physicians posted about

STARBOARD: encorafenib + binimetinib + pembrolizumab, first-line BRAF V600-mutant melanoma

Randomized, double-blind Phase 3 of the triplet vs placebo plus pembrolizumab in unresectable or metastatic BRAF V600-mutant melanoma, presented by Dirk Schadendorf (2071O). (ESMO 2026 program) Encorafenib plus binimetinib is FDA approved for BRAF V600E/K-mutant unresectable or metastatic melanoma; the triplet with pembrolizumab is investigational. Physicians called the PFS result impressive and questioned the control arm (pembrolizumab alone rather than ipilimumab-nivolumab) and the immature OS.

Strong PFS, open questions on the comparator and OS

Yago Garitaonaindía @YGaritaonaindia

medical oncologist; translational research fellow, Copenhagen · Oct 23

🔥 STARBOARD at #ESMO26: enco + bini + pembro vs placebo + pembro, 1L BRAF V600 melanoma (n=220) 🖋️ Dirk Schadendorf ➡️ ORR 70% vs 33% | mPFS 33.0 vs 3.4 mo, HR 0.33 | OS HR 0.71 (90% CI 0.48-1.05) 
☣️ G3-4 TEAEs 70% vs 39% | enco/bini discontinuation 43% My two issues:
⚠️ Was pembro mono the right control? Fit BRAF-mutant pts get ipi-nivo 
⚠️ Too few events for OS at 31 mo FU, though the trend favours the triplet @myESMO @_SEOM @OncoAlert @LARVOL

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Mario Balsa @MarioBalsaMD

medical oncologist, melanoma, Hospital Clínic Barcelona · Oct 23

My top 🥈💎 #Melanoma #ESMO26 STARBOARD - Triplet therapy in BRAF V600 melanoma: enco + bini + pembro vs pembro alone in 1L. 💥 ORR: 70% vs 32.7% || mPFS: 33.0 vs 3.4 mo ▪️G3/4 TEAEs: 70% vs 39% OS: positive trend, but immature after early trial closure. Impressive PFS! But STARBOARD has not reached the OS shore yet⚓ @OncoAlert @OncoReporte @myESMO @_SEOM @GrupoMelanoma

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Mustafa Özdoğan, MD @ozdogan_md

medical oncologist, Türkiye · Oct 23

🔥 THE RESULT IS IMPRESSIVE. THE COMPARATOR IS THE REAL QUESTION. In BRAF V600 melanoma, upfront BRAF/MEK + anti–PD-1 delivered striking disease control. But does beating anti–PD-1 monotherapy answer today’s first-line question? Presented by Dirk Schadendorf. #ESMO26 #Melanoma

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IOV-COM-202 cohort 1A: lifileucel + pembrolizumab in ICI-naive advanced melanoma

Final results from the lifileucel (TIL) plus pembrolizumab cohort, presented by Andrew J. Furness (2072O). (ESMO 2026 program) Lifileucel (Amtagvi) is FDA approved for advanced melanoma after anti-PD-1 therapy; first-line use with pembrolizumab is investigational. Physicians noted the responses and durability, and raised toxicity and the choice of comparator for the Phase 3 trial.

GC101 TIL (MIZAR-003): IL-2-free TIL in anti-PD-1-resistant melanoma

Extended follow-up of a randomized, open-label, pivotal phase II trial of GC101 TIL vs chemotherapy, presented by Lu Si (LBA55). (ESMO 2026 program) Most patients had acral or mucosal melanoma. GC101 TIL is not FDA approved. Physicians focused on the IL-2-free, lower-intensity lymphodepletion approach, the chemotherapy comparator and how GC101 compares with lifileucel.

IMA203CD8: PRAME-directed TCR T cells, phase 1

Phase 1 trial in HLA-A*02:01-positive, PRAME-positive solid tumors, including a melanoma cohort, presented by Antonia Busse. (presented slide) IMA203CD8 is investigational. Physicians highlighted durable responses in heavily pretreated patients.

HBI-8000-303: HBI-8000 + nivolumab in advanced melanoma

Randomized Phase 3 of nivolumab plus HBI-8000 or placebo, presented by Nikhil I. Khushalani (LBA54). (ESMO 2026 program) HBI-8000 plus nivolumab is investigational in melanoma. One physician post discussed it, raising toxicity and OS.

STARBOARD, IOV-COM-202, GC101 TIL, IMA203CD8 and HBI-8000-303 slides on the melanoma slide page.

KOL Voices: top physicians in melanoma at ESMO 2026

From the melanoma tab of the Top KOLs leaderboard on the conference page. One verbatim line each, labeled with the trial it is about; follow the link for the full post.

Melanoma leaderboard, October 25

Mario Balsa @MarioBalsaMD

medical oncologist, melanoma, Hospital Clínic Barcelona · leaderboard #1, 31.0K impressions, 36 posts · Oct 24

on INTerpath-001 →

“A clinically meaningful new mechanism, but the real question now is positioning”

Read the full post on X ↗

Balazs Halmos @BalazsHalmosMD

thoracic oncologist · leaderboard #2, 13.4K impressions, 9 posts · Oct 24

on INTerpath-001 →

“Indeed a landmark trial for precision medicine and hopefully not too Long before we see confirmation in nsclc/other trials!”

Read the full post on X ↗

Yago Garitaonaindía @YGaritaonaindia

medical oncologist; translational research fellow, Copenhagen · leaderboard #3, 11.7K impressions, 15 posts · Oct 24

on INTerpath-001 →

“Practice-changing? For a population, yes.”

Read the full post on X ↗

Professor Georgina Long AO (Bluesky @gvlongphdmd) @ProfGLongMIA

medical oncologist, Melanoma Institute Australia; INTerpath-001 presenter · leaderboard #5, 10.0K impressions, 2 posts · Oct 25

on INTerpath-001 →

“Having succeeded in melanoma, this proof of concept could mark the beginning of a foundational shift in how we treat cancer.”

Read the full post on X ↗

Mark Yarchoan @MarkYarchoan

physician-scientist, Johns Hopkins · leaderboard #7, 5.9K impressions, 2 posts · Oct 22

on INTerpath-001 →

“This hazard ratio puts it in the company of the most paradigm-changing adjuvant trials in oncology history”

Read the full post on X ↗

Yannick Buccella MD @YannickBuccella

GI and molecular oncologist, Zurich · leaderboard #8, 5.6K impressions, 3 posts · Oct 23

on INTerpath-001 →

“Nobody cured melanoma this week.”

Read the full post on X ↗

Eric D Whitman, MD @Melanoma_doctor

melanoma surgeon and IO specialist, Atlantic Health System · leaderboard #9, 4.2K impressions, 2 posts · Oct 23

on NADINA →

“Actually, neoadjuvant pembro is not necessarily the standard for resectable Stage III; based on the NADINA study and on clinical judgement, ipi/nivo combo neoadjuvant therapy is often used instead of single agent pembro.”

Read the full post on X ↗

What’s yet to come: melanoma at ESMO 2026, October 26–27

Times are Madrid time.

No melanoma late-breaking abstracts are scheduled for October 26–27. Regulatory next step on INTerpath-001: Merck and Moderna plan to engage regulators on filings. INTerpath-001 OS follow-up is ongoing. Physician posts on these sessions will appear on the ESMO 2026 trials page and the melanoma slide library.

FAQ

Which melanoma trials did physicians discuss most at ESMO 2026?

By physician posts on X on October 23-25, INTerpath-001 led by a wide margin (109 posts from 70 physicians), followed by NADINA (3-year update), STARBOARD, IOV-COM-202, GC101 TIL (MIZAR-003), PLUG-IN GEM 2301, IMA203CD8, FS222, HERTHENA-PanTumor01 and HBI-8000-303.

What did INTerpath-001 show?

Adding intismeran autogene to adjuvant pembrolizumab in resected stage IIB-IV melanoma gave an RFS HR of 0.58 (95% CI 0.45-0.75); 24-month RFS was 82.2% vs 70.0%. DMFS HR was 0.62. OS is immature (HR 0.77, P=0.33) (ESMO 2026 LBA1, data cutoff June 30, 2026).

What was presented on NADINA at ESMO 2026?

A 3-year update of the phase 3 NADINA trial of neoadjuvant ipilimumab plus nivolumab vs surgery and adjuvant nivolumab in resectable macroscopic stage III melanoma, presented by Sonja Witteveen (2076RO) on October 25. Neoadjuvant use is not an FDA-labeled indication.

Is intismeran autogene approved?

No. Intismeran autogene is investigational and not approved by the FDA or any other regulator. Merck and Moderna plan to engage regulators on filings.

What melanoma sessions remain at ESMO 2026?

On October 26: a Challenge your expert session on NGS in melanoma (Georgina V. Long, Rebecca Lee, chair Bart Neyns) and two translational rapid orals (4250RO, 4251RO). On October 27: congress highlights for melanoma and other skin tumors (Sapna P. Patel).

Related ESMO 2026 pages

• ESMO 2026 melanoma slide library
• ESMO 2026 trials: physician posts by trial
• ESMO 2026 conference page
• INTerpath-001 trial page
• NADINA trial page