π¬ Melanoma Intelligence Digest β Week 2026-W41
INMC five-year pooled data show major pathological response after neoadjuvant immunotherapy carries ~98% 5-year OS with no added benefit from adjuvant ICI, FDA granted accelerated approval to vusolimogene oderparepvec plus nivolumab after anti-PD-1 failure, and tovorafenib showed 43% ORR in BRAF/CRAF fusion-altered tumors.
β‘ TL;DR
π Publications
- Five-year survival with neoadjuvant therapy in melanoma: updated pooled analysis from the International Neoadjuvant Melanoma Consortium (INMC). β Pooled analysis of 1,038 patients treated with neoadjuvant ICIs (n=735), BRAF and MEK inhibitors (n=119) or ICI plus any targeted therapy (n=184) across 26 international sites, 755 (72.7%) in trials and 283 (27.3%) nontrial
- Type II RAF Inhibitor Tovorafenib in Recurrent/Refractory Melanoma or Other Solid Tumors With BRAF Fusions or CRAF/RAF1 Fusions or Amplification: Phase II FIRELIGHT-1 Substudy. β Phase II DAY101-102a substudy of FIRELIGHT-1 (NCT04985604) enrolled patients aged 12 years or older with recurrent/refractory solid tumors harboring a BRAF fusion or CRAF fusion or amplification into a melanoma cohort or tumor-agnostic cohort, with ORR as primary endpoint
π¦ Twitter / π¦ Bluesky
- Blood-based neoantigen identification could remove the tumor biopsy requirement for personalized vaccines β Personalized neoantigen vaccines have improved outcomes in refractory malignant melanoma and in pilot studies of pancreatic cancer, glioblastoma, renal cell carcinoma and triple negative breast cancer
- INMC five-year pooled analysis: major pathological response after neoadjuvant immunotherapy means ~98% 5-year survival and no gain from adjuvant continuation β The pooled analysis included 1,038 patients with resectable melanoma treated before surgery; among the 735 who received immunotherapy, 58% had little or no viable tumor left at surgery
- False-negative initial melanoma diagnosis associated with an average loss of 8.2 years of life in a 9,063-patient German cohort β A German study of 9,063 melanoma patients found that among 206 patients with a missed diagnosis, the median delay to correct diagnosis was 24 months
- EVX-01 plus pembrolizumab two-year data: 75% objective response rate with responses maintained off anti-PD-1 β In a phase 2 trial of EVX-01 plus pembrolizumab in advanced melanoma, 12 of 16 patients had objective clinical responses at two years, a 75% objective response rate, including four complete responses
Full details below β
π What's Being Published
Cancer and the microbiome: from association to intervention. β Moradi Ali et al., Lancet Oncol
This review describes the gut microbiome as a clinically modifiable determinant of efficacy and toxicity across systemic cancer therapies, with the most mature evidence in patients receiving immune checkpoint inhibitors. In melanoma, non-small-cell lung cancer and renal cell carcinoma, higher microbial diversity, ecological stability and enrichment of immunostimulatory pathways have been associated with improved ICI response and survival. Antibiotics and proton pump inhibitors are linked to inferior outcomes because they disrupt the microbiome. Faecal microbiota transplantation, dietary modifications, prebiotics, probiotics and live biotherapeutic products remain investigational.
Clinical bottom line: For melanoma patients starting checkpoint blockade, avoid unnecessary antibiotics and proton pump inhibitors, and treat microbiome-directed interventions as investigational only.
Five-year survival with neoadjuvant therapy in melanoma: updated pooled analysis from the International Neoadjuvant Melanoma Consortium (INMC). β Long Georgina V et al., Nat Med
Across 1,038 patients from 26 international sites, MPR was achieved in 57.8% with ICIs, 51.4% with BRAF/MEKis and 44.6% with ICI + TT, and PD-1 + IO elicited higher MPR rates than PD-1 alone (61.4% versus 49.5%). The 5-year RFS rate was 61.0% with PD-1 alone, 73.9% with PD-1 + IO, 37.4% with BRAF/MEKis and 76.4% with ICI + TT; 5-year OS rates were 83.3%, 87.5%, 69.8% and 83.9%, respectively. ICI-treated patients with MPR had 5-year OS of 98.8% with PD-1 alone and 97.9% with PD-1 + IO and gained no benefit from continuing ICIs into the adjuvant setting. Neoadjuvant ICIs were also active in BRAF-mutant melanoma (MPR 46.3%), acral melanoma (38.1%), in-transit metastases (66.7%) and oligometastases (41.2%).
Clinical bottom line: Patients with a major pathological response after neoadjuvant checkpoint blockade have near-universal 5-year survival and can reasonably stop therapy after surgery; BRAF/MEK inhibitor-based neoadjuvant therapy should not be used.
Pembrolizumab vs Nivolumab as Initial Treatment for Advanced, Unresectable, or Metastatic Melanoma. β Strohbehn Garth W et al., JAMA Netw Open
This comparative effectiveness research study examines outcomes associated with pembrolizumab and nivolumab among US veterans with advanced, unresectable, or metastatic melanoma. The available abstract text reports the study design only.
Clinical bottom line: A veterans-cohort comparison of the two single-agent anti-PD-1 options in advanced melanoma; with only the design reported in the available abstract text, it does not by itself change agent selection.
Anti-PD-1 Therapy and Long-Term Toxic Effects Among Patients With Melanoma. β Kankaria Roma A et al., JAMA Netw Open
Among 303 patients with stage III to IV melanoma given adjuvant anti-PD-1 at 7 institutions in the US and Australia, 220 (73%) developed acute irAEs and 146 (48%) developed chronic irAEs, most commonly hypothyroidism (45 of 146 [31%]), arthritis (25 of 146 [17%]) and dermatitis (17 of 146 [12%]). Chronic irAEs had later onset (median 153.0 vs 99.0 days; P = .006) and more frequent corticosteroid exposure (35% vs 24%; P = .03) than nonchronic irAEs. Corticosteroid-treated patients with earlier-onset irAEs had higher odds of chronic irAEs (odds ratio 3.00; 95% CI 1.45-6.22), and eight cytokines, including VEGFA and CCL19, were elevated after FDR adjustment.
Clinical bottom line: Nearly half of patients given adjuvant anti-PD-1 for resected melanoma carry immune toxicity beyond therapy cessation, so survivorship plans must include long-term irAE monitoring, particularly when irAEs required corticosteroids.
Type II RAF Inhibitor Tovorafenib in Recurrent/Refractory Melanoma or Other Solid Tumors With BRAF Fusions or CRAF/RAF1 Fusions or Amplification: Phase II FIRELIGHT-1 Substudy. β Vieito Maria et al., JCO Precis Oncol
Twenty-three patients with BRAF fusion or CRAF fusion or amplification were enrolled (eight melanoma, 15 tumor-agnostic; 57% with β₯2 prior lines). The ORR was 43% (10/23), including 50% (4/8) in melanoma and 40% (6/15) in other tumors, with median time to response of 1.8 months and median duration of response of 9.2 months. The most common treatment-related adverse events were anemia (39%), pruritus (30%), increased creatine phosphokinase (26%) and rash (26%).
Clinical bottom line: In the rare melanoma patient whose tumor carries a BRAF or CRAF fusion or CRAF amplification rather than BRAF V600, weekly tovorafenib is a reasonable targeted option, though the cohorts are very small.
π Every paper considered this week, including the ones that didnβt make it β
π£οΈ What People Were Discussing This Week
How these are chosen: filtered for clinical relevance, grouped by the new development discussed, then ordered by engagement (bookmarks and reposts).
Blood-based neoantigen identification could remove the tumor biopsy requirement for personalized vaccines
Personalized neoantigen vaccines have improved outcomes in refractory melanoma, but they currently require a tumor biopsy; a new study shows antigens can instead be obtained from a blood sample. This comes alongside the first positive Phase 3 trial (N=1137) of an individualized neoantigen therapy, intismeran plus pembrolizumab in resected melanoma, which met RFS and DMFS endpoints, although hazard ratio data remain undisclosed and the therapy is not approved. The open question is which resected patients should be offered personalized vaccine trials while the Phase 3 hazard ratios are still unreported.
Discussed by: @EricTopol, @ozdogan_md, @curijoey
Sources cited: Peripheral Blood as the Sole Source for Cancer Neoantigen and Reactive T-Cell Discovery (Cancer Discovery, 2026) Β· A neoantigen vaccine generates antitumour immunity in renal cell carcinoma (Nature, 2025) Β· Merck press release
INMC five-year pooled analysis: major pathological response after neoadjuvant immunotherapy means ~98% 5-year survival and no gain from adjuvant continuation
In this pooled real-world and trial cohort, patients with a major pathological response after neoadjuvant immunotherapy had near-complete 5-year overall survival, and continuing immunotherapy after surgery added nothing for these responders. Clinicians framed it as "treat smarter, not longer," while noting the analysis is not randomized and that prospective trials are needed. The debate is whether MPR already justifies stopping therapy at surgery or whether adjuvant immunotherapy should continue until a prospective de-escalation trial reports.
Key numbers: 5-yr OS with MPR 98.8% (PD-1 alone) vs 97.9% (combination) Β· 5-yr RFS in MPR 90.8% vs 90.6% with vs without adjuvant IO
Discussed by: @ilyassahinMD, @MelanomaAus, @DrTrevanFischer, @ManuelDomine
Sources cited: Five-year survival with neoadjuvant therapy in melanoma: updated pooled analysis from the⦠(Nat Med)
False-negative initial melanoma diagnosis associated with an average loss of 8.2 years of life in a 9,063-patient German cohort
In a German study of 9,063 melanoma patients, the 206 with a missed diagnosis waited a median of 24 months for the correct diagnosis and had significantly lower 10-year recurrence-free and melanoma-specific survival. An initial false-negative diagnosis was associated with an average loss of 8.2 years of life. Clinicians are debating whether a 2-year diagnostic delay changes the outcome, and whether a benign-reported or nondiagnostic initial biopsy of a clinically suspicious lesion should trigger mandatory re-biopsy or second pathology review.
Discussed by: @weoncologists, @DrVilmaPBarcia
Sources cited: Years of life lost in patients with a false-negative diagnosis of primary melanoma. A pro⦠(Nature Communications, 2026)
EVX-01 plus pembrolizumab two-year data: 75% objective response rate with responses maintained off anti-PD-1
In the phase 2 trial of EVX-01 plus pembrolizumab in advanced melanoma, most patients had objective responses at two years, including complete responses, and nearly all were still responding with no relapses; patients received EVX-01 alone in the third year. Further oral and poster presentations are scheduled in Phoenix. With such a small cohort, the debate is how much weight the response rate should carry when counseling patients about personalized vaccine trials versus established combinations.
Key numbers: ORR 75% (12 of 16) Β· four complete responses Β· 92% still responding at two years, no relapses
Discussed by: @sitcancer, @sitcancer
π₯ Top Ranked Tweets
ClinicalOncologyNews @ClinOncNews
New hope in advanced melanoma: FDA grants accelerated approval to vusolimogene oderparepvec + nivolumab after PD-1 therapy. IGNYTE showed a 24.2% response rate and 14.1-month median duration. #Melanoma #FDA
https://t.co/KT1aNidfh0 https://t.co/WuepkZcdpJ
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ClinicalOncologyNews @ClinOncNews
FDA grants accelerated approval to Tudriqev (vusolimogene oderparepvec) plus nivolumab for advanced melanoma that progressed on anti-PD-1 therapy. Nearly 1 in 4 evaluable patients responded in the pivotal trial.
https://t.co/RkXjSmwpMN
#Melanoma #Immunotherapy https://t.co/caxtn7Avyg
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G Curigliano MD PhD @curijoey
Donβt miss the data at #ESMO2026!!!!!
[Quoting @PTarantinoMD: Positive 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]
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G Curigliano MD PhD @curijoey
Donβt miss the data at #ESMO2026
[Quoting @DrChoueiri: JUST IN and via @Merck + @moderna_tx: A landmark moment for cancer immunotherapy. π―
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 patientβs tumor seemed aspirational. Now we have the first positive Phase 3 trial (N=1137) of an individualized neoantigen therapyβand 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 fieldβand hopefully for our patients. π
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]
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Melanoma Institute Australia @MelanomaAus
An international study led by Professor Georgina Long AO has been published in Nature Medicine, providing the first five-year survival outcomes for patients with melanoma treated with neoadjuvant therapy in clinical trials and routine practice.
"Thrilled to share that our international collaboration has just been published in Nature Medicine!
We analysed data from 1,038 patientsΒ across 26 centers worldwide treated with neoadjuvant immunotherapy for melanoma on trials and as standard therapy. It confirms what we've hoped: trial results translate into everyday practice.
Key findings:
*Patients whose tumors responded well to immunotherapy before surgery (a "major pathological response") had outstanding 5-year survival: 98.8%Β with PD-1 therapy alone, 97.9%Β with combination therapy
*Continuing immunotherapy after surgery gave these responders no extra benefit
*Immunotherapy before surgery also worked in melanoma types that are traditionally harder to treat β BRAF-mutant, acral, in-transit, and oligometastatic disease
Our next step is to identify who needs less treatment (avoiding unnecessary toxicity) and who needs a different approach. This is real progress toward personalised care and being tested in the NeoIRENIE trial.
Deep thanks to our incredible global team of collaborators." - Prof Georgina Long Β
Other authors from Melanoma Institute Australia faculty and team include Assoc Prof Ines Pires da Silva, Kristen Perry, Prof Serigne Lo, Assoc Prof Matteo Carlino, Assoc Prof Alexander van Akkooi, Dr Robert Rawson and Prof Alexander Menzies.
Read more and see publication > https://t.co/z9NULTGvM2
#Immunotherapy #MelanomaResearch #Oncology
@sydney_uni @syd_health
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Dermatology Times @DermTimesNow
π¨ Merck & Modernaβs phase 3 trial found #intismeran + #pembrolizumab significantly improved recurrence-free and distant metastasis-free survival in resected high-risk #melanoma, marking a milestone for personalized mRNA therapy.
https://t.co/8zZ6sgWP9N #SkinCancer #DermTwitter
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Mustafa ΓzdoΔan, MD @ozdogan_md
A milestone for cancer vaccines: #intismeran + #pembrolizumab delivered the worldβs first positive Phase 3 result for a personalized mRNA cancer therapy in resected melanoma. RFS and DMFS were met, but HR data remain undisclosed; the therapy is not approved.
#Melanoma #mRNA https://t.co/eDOddOhGgj
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Elad Sharon @EladSharonMD
RT @EricTopol: Personalized neoantigen vaccines have already been shown to improve outcomes for refractory malignant melanoma and in pilot studies of pancreatic cancer, glioblastoma, renal cell carcinoma and triple negative breast cancer. But they require a tumor biopsy to identify the antigens. A new study shows it's possible to get this from a blood sample.
https://t.co/v2cupJHwZA
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Eric Topol @EricTopol
Personalized neoantigen vaccines have already been shown to improve outcomes for refractory malignant melanoma and in pilot studies of pancreatic cancer, glioblastoma, renal cell carcinoma and triple negative breast cancer. But they require a tumor biopsy to identify the antigens. A new study shows it's possible to get this from a blood sample.
https://t.co/v2cupJHwZA
π 81 β€οΈ 253 π 62 π 33,527
Oncology Brothers @OncBrothers
RT @ilyassahinMD: Big melanoma data in @NatureMedicine π
A pooled analysis of 1,038 patients with resectable melanoma treated before surgery. Among the 735 who received immunotherapy, 58% had little or no viable tumor left at surgery.
Those patients? ~98% alive at 5 years.
And their 5-year recurrence-free survival was similar with or without additional immunotherapy after surgery (90.8% vs 90.6%).
So if treatment already worked this well, do patients need more?
Not randomized, so prospective trials are needed. But very encouraging.
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John Cramer, MD @Jdcramer
RT @ilyassahinMD: Big melanoma data in @NatureMedicine π
A pooled analysis of 1,038 patients with resectable melanoma treated before surgery. Among the 735 who received immunotherapy, 58% had little or no viable tumor left at surgery.
Those patients? ~98% alive at 5 years.
And their 5-year recurrence-free survival was similar with or without additional immunotherapy after surgery (90.8% vs 90.6%).
So if treatment already worked this well, do patients need more?
Not randomized, so prospective trials are needed. But very encouraging.
π 35 β€οΈ 83 π 22 π 11,401
Paolo Tarantino @PTarantinoMD
RT @ilyassahinMD: Big melanoma data in @NatureMedicine π
A pooled analysis of 1,038 patients with resectable melanoma treated before surgery. Among the 735 who received immunotherapy, 58% had little or no viable tumor left at surgery.
Those patients? ~98% alive at 5 years.
And their 5-year recurrence-free survival was similar with or without additional immunotherapy after surgery (90.8% vs 90.6%).
So if treatment already worked this well, do patients need more?
Not randomized, so prospective trials are needed. But very encouraging.
π 35 β€οΈ 83 π 22 π 11,401
ilyas sahin, MD @ilyassahinMD
Big melanoma data in @NatureMedicine π
A pooled analysis of 1,038 patients with resectable melanoma treated before surgery. Among the 735 who received immunotherapy, 58% had little or no viable tumor left at surgery.
Those patients? ~98% alive at 5 years.
And their 5-year recurrence-free survival was similar with or without additional immunotherapy after surgery (90.8% vs 90.6%).
So if treatment already worked this well, do patients need more?
Not randomized, so prospective trials are needed. But very encouraging.
π 35 β€οΈ 83 π 22 π 11,402
Lindsey Draper @Lindsey__Draper
@drkomanduri and I share our thoughts on lifileucel in clinical practiceβand the challenge of reducing patient attritionβin our commentary in Transplantation and Cellular Therapy.
https://t.co/v4DmAgcHhB
#TILtherapy #Melanoma #CellTherapy
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Oncology Tube @oncologytube
VIDEO: ESMO Oct 23β27 Madrid β which Top 10 LBAs for US clinics? πΈ
https://t.co/4zqOT4u04I
β #1 INTerpath-001 melanoma RFS+DMFS met (LBA1)
#2 VOLGA MIBC β EFS+OS improved; FDA Priority Review
β HRs/medians embargoed
Countdown #10β#1.
#ESMO2026 #LBA #Oncology https://t.co/GZ2npxHn0t
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π§ͺ Newly Recruiting Trials
1 trial (1 phase II) opened this week, testing pembrolizumab versus ipilimumab plus nivolumab
Phase 2 Β· UNC Lineberger Comprehensive Cancer Center Β· pembrolizumab versus ipilimumab plus nivolumab Β· North Carolina Β· CT.gov β
Open it on the trials page β
Agent descriptions from the NCI Thesaurus.
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