📬 Melanoma Intelligence Digest — Week 2026-W33

FDA granted accelerated approval to RP1 (Tudriqev) plus nivolumab for advanced cutaneous melanoma after anti-PD-1 progression, and a SECOMBIT biomarker analysis reported circulating thymidine kinase activity stratifies survival and optimal treatment sequencing in BRAF-mutant metastatic melanoma.

⚡ TL;DR

📄 Publications

Circulating thymidine kinase activity predicts survival and optimal treatment sequencing in BRAF-mutated metastatic melanoma in the SECOMBIT trial. — In TKa-low (n=41) vs TKa-high (n=40) patients, 5-year first PFS was 43.3% vs 27.5% (p=0.062), total PFS 60.8% vs 35.0% (P=0.004) and OS 70.7% vs 36.9% (p<0.001)

🐦 Twitter / 🦋 Bluesky

FDA grants accelerated approval to RP1 (Tudriqev) plus nivolumab for advanced melanoma after anti-PD-1 progression — FDA granted accelerated approval to RP1 (Tudriqev) plus nivolumab for advanced melanoma after progression on anti-PD-1 therapy, following two prior FDA rejections and a 10-3 positive ODAC vote
Circulating thymidine kinase activity in SECOMBIT separates BRAF-mutant melanoma survival and points TKa-high patients to the sandwich sequence — In the SECOMBIT subset (n=81), 5-year OS was 70.7% vs 36.9% (HR 3.08) and 5-year total PFS 60.8% vs 35.0% (HR 2.47) by median TKa split, independent of LDH
Five-year update of KEYNOTE-942 for intismeran autogene plus pembrolizumab in high-risk resected melanoma is published — JCO published the 5-year update of the randomized phase 2b KEYNOTE-942 study of intismeran autogene plus pembrolizumab versus pembrolizumab alone in high-risk resected melanoma

Full details below ↓

📄 What's Being Published

Manuscripts:

Circulating thymidine kinase activity predicts survival and optimal treatment sequencing in BRAF-mutated metastatic melanoma in the SECOMBIT trial. — Helgadottir Hildur et al., Clin Cancer Res

In TKa-low (n=41) vs TKa-high (n=40) patients, 5-year first PFS was 43.3% vs 27.5% (p=0.062), total PFS was 60.8% vs 35.0% (P=0.004), and OS was 70.7% vs 36.9% (p<0.001). Longitudinal analyses revealed an early TKa rise in the majority of patients receiving ICI and increasing TKa levels at disease progression. TKa-high patients showed improved outcomes with the sandwich strategy compared with other sequences.

Clinical bottom line: A simple serum marker of proliferation separates BRAF-mutant metastatic melanoma patients by 5-year OS (70.7% vs 36.9%) and points TKa-high patients toward short targeted-therapy induction before immunotherapy rather than upfront immunotherapy.

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Circulating B cell and T cell activation states predict clinical outcomes in melanoma and reveal dynamic immune reinvigoration with checkpoint inhibitor immunotherapy. — Booth Lucy et al., J Immunother Cancer

Pretreatment elevated PD-1+ T cells predicted immune-related adverse events, whereas VEGF+TGF-β+ double-negative T cells were enriched in patients without subsequent toxicity. On-treatment, increased class-switched memory (IgG2+) B cells and activated T cells predicted improved survival, while persistent naive and double-negative B cells were associated with poorer outcomes. Anti-PD-1 monotherapy expanded naive (CD21hi) B cells and global T cells, whereas anti-PD-1/anti-LAG-3 combination contracted memory B cells.

Clinical bottom line: Peripheral blood B-cell and T-cell activation states, not T cells alone, track both checkpoint inhibitor benefit and toxicity risk in melanoma and are candidate blood-based monitoring markers.

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🗣️ 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).

FDA grants accelerated approval to RP1 (Tudriqev) plus nivolumab for advanced melanoma after anti-PD-1 progression

The FDA granted accelerated approval to vusolimogene oderparepvec-wtpg (Tudriqev) plus nivolumab for adults with unresectable advanced cutaneous melanoma who progressed on a PD-1-blocking antibody-based regimen, based on the IGNYTE trial — following 2 prior complete response letters, 3 submissions, and a July 30 10–3 vote by the Cellular, Tissue, and Gene Therapies Advisory Committee. Reported efficacy figures across sources include an ORR of 33.6% with a duration of response greater than 35 months in the IGNYTE trial, with label-cited figures of 24% response and a median response duration of 14.1 months; a separate source cited a 25% response rate with responses lasting a median of nearly 14 months. Clinicians are weighing how an ORR of 24% and a median duration of response of 14.1 months position RP1 plus nivolumab against other post-anti-PD-1 options.

Discussed by: @OncoAlert, @CureMelanoma, @ASCOPost, @OncoAlert, @Dr_ElvinaA, @OncoAlert, @MelanomaReAlli, @Melanoma_doctor, @OncLive, @CancerNetwrk

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Circulating thymidine kinase activity in SECOMBIT separates BRAF-mutant melanoma survival and points TKa-high patients to the sandwich sequence

In the SECOMBIT subset (n=81), splitting by median TKa yielded a 5-year OS of 70.7% vs 36.9% (HR 3.08) and a 5-year total PFS of 60.8% vs 35.0% (HR 2.47), both independent of LDH. Notably, 54% of TKa-high patients had a normal LDH, identifying aggressive biology that standard laboratory markers would otherwise miss; TKa also increased at progression, consistent with use as a dynamic disease marker. The central clinical question is whether, given that more than half of TKa-high patients carry a normal LDH, a proliferation marker should replace LDH as the trigger for short targeted-therapy induction before immunotherapy.

Discussed by: @YGaritaonaindia, @OncoAlert

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Five-year update of KEYNOTE-942 for intismeran autogene plus pembrolizumab in high-risk resected melanoma is published

JCO published the 5-year update of the randomized phase 2b KEYNOTE-942 study of intismeran autogene plus pembrolizumab versus pembrolizumab alone in high-risk resected melanoma, co-authored by Adnan Khattak. Oncologists are considering whether a 5-year randomized phase 2b readout for an individualized neoantigen therapy combined with pembrolizumab changes expectations for the ongoing phase 3 adjuvant program.

Discussed by: @JCO_ASCO, @JCO_ASCO

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🔥 Top Ranked Tweets

OncoAlert @OncoAlert

RT @DrChoueiri: JUST IN: Big news in #melanoma today.

@US_FDA grants accelerated approval to RP1 (Tudriqev) + nivolumab for advanced melanoma after progression on anti–PD-1 therapy. Drug from @Replimune

An oncolytic immunotherapy injected directly into tumors—aiming to turn the tumor itself into an immune stimulus.

Quite a regulatory journey: 2 prior FDA rejections → 10–3 positive ODAC vote → approval.

Important new option for a difficult-to-treat population. And an important reminder that promising science sometimes takes a complicated road to patients.

Link: https://t.co/YB7n6gFzsw

Confirmatory Phase 3 ongoing.

@OncoAlert @OncBrothers @DanaFarber_GU @DanaFarber @harvardmed @OmidHamidMD @HTawbi_MDPhD @DrSapnaPatel

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