๐ฌ Melanoma Intelligence Digest โ Week 2026-W27
This week spans new melanoma genetics, real-world ITM and uveal melanoma analyses, post-TIL checkpoint salvage data, a retraction of the infusion timing study, and RP1 regulatory progress.
โก TL;DR
๐ Publications
- Predicting immune-related thyroiditis using polygenic risk scores in patients with advanced melanoma. โ Germline DNA from 744 participants in a phase 3 adjuvant trial was analyzed
- Percutaneous hepatic perfusion versus best alternative care as treatment for metastatic uveal melanoma: A meta-analysis. โ PHP higher ORR 47.4% vs 6.0% versus best alternative care
- Response and survival in unresectable in-transit metastatic melanoma according to treatment strategy. โ ORR comparable: anti-PD1 53.1%, T-VEC 52.2%, BRAF(/MEK)i 62.7%
- Immune checkpoint inhibitor therapy after tumor-infiltrating lymphocytes in unresectable melanoma. โ ORR for ICI after TIL progression was 11% (n=14), with 3 complete responses
- Addressing Biases in Analysis of Time of Infusion: NCI/SWOG Trial S1404 Among Participants With High-Risk Resectable Melanoma Who Received Adjuvant Anti-PD-1 Therapy. โ 628 participants received pembrolizumab with time of first infusion recorded
๐ฆ Twitter / ๐ฆ Bluesky
- Update: Nature Medicine retracts the immunotherapy infusion-timing study, removing the only prospective time-of-day evidence โ The article claiming early morning immunotherapy works better than afternoon is now retracted, removing the only prospective evidence that time-of-day matters
- Liquid EcoTyper infers spatial tumor ecotypes from cfDNA methylation tied to immunotherapy benefit in melanoma โ Liquid EcoTyper infers spatial tumor ecotypes from cfDNA methylation associated with immunotherapy benefit in melanoma
- Gut microbiome associated with recurrence-free survival in resected high-risk melanoma on adjuvant immunotherapy โ Gut microbiome is associated with recurrence-free survival in patients with resected high-risk melanoma receiving adjuvant checkpoint blockade
- Update: FDA accepts third RP1 plus nivolumab BLA resubmission with priority review and August 2 PDUFA date โ The FDA accepted the resubmission of the RP1 plus nivolumab BLA for advanced melanoma with an accelerated review and a response goal date of August 2
- Imneskibart Phase 2 data in checkpoint-refractory metastatic melanoma at ASCO26 โ Phase 2 imneskibart in doublet checkpoint inhibitor-refractory metastatic melanoma showed a 33% ORR and 67% DCR
Full details below โ
๐ What's Being Published
Predicting immune-related thyroiditis using polygenic risk scores in patients with advanced melanoma. โ Tarhini Ahmad A et al., J Immunother Cancer
Germline DNA from 744 participants in a phase 3 adjuvant trial was analyzed following genome-wide genotyping. The custom 10-SNP polygenic risk score achieved an area under the curve of 0.82 for thyroiditis risk discrimination, demonstrating stronger performance than prior approaches.
Clinical bottom line: A custom 10-SNP polygenic risk score predicts immune-related thyroiditis after checkpoint therapy and supports risk-adapted monitoring.
Percutaneous hepatic perfusion versus best alternative care as treatment for metastatic uveal melanoma: A meta-analysis. โ van den Hoek Linde et al., Eur J Cancer
Percutaneous hepatic perfusion (PHP) was associated with a higher ORR (47.4% vs 6.0%), longer 1-year PFS (30.1% vs 6.4%), and median PFS (7.7 vs 2.6 months) compared with best alternative care. The pooled 2-year OS was 35.4% (95% CI 28.5โ42.4%) for PHP and 28.1% (95% CI 9.6โ50.2%) for best alternative care, with median OS of 17.3 months (95% CI 11.8โ22.8) and 14.0 months (95% CI 4.3โ23.6), respectively.
Clinical bottom line: PHP improves response and PFS over best alternative care in metastatic uveal melanoma but shows no clear survival benefit.
Response and survival in unresectable in-transit metastatic melanoma according to treatment strategy. โ Boreel Cato et al., Eur J Cancer
ORR were comparable between treatments: anti-PD1 53.1%, T-VEC 52.2%, and BRAF(/MEK)i 62.7%. However, median PFS was significantly shorter for T-VEC (5.6 months; 95% CI 4.2โ8.1) than for anti-PD1 (8.1 months; 95% CI 5.9โ13.8) and BRAF(/MEK)i (9.2 months; 95% CI 6.9โ14.3).
Clinical bottom line: In unresectable in-transit melanoma, anti-PD1, T-VEC, and BRAF(/MEK)i all produce durable responses, with treatment choice driven by patient and disease characteristics.
Immune checkpoint inhibitor therapy after tumor-infiltrating lymphocytes in unresectable melanoma. โ Smithy James William et al., J Immunother Cancer
Among 133 patients assessed for response to ICI therapy after progression on TIL therapy, the ORR was 11% (n=14; 95% CI 5.9% to 17%), including 3 complete responses (2.3%) and 11 partial responses (8.3%). At a median follow-up among survivors of 21 months, median OS from post-TIL ICI was 8.8 months (95% CI 6.5 to 12 months).
Clinical bottom line: Checkpoint inhibition after TIL progression has limited efficacy without synergistic toxicity, underlining the need for novel therapies in this setting.
Addressing Biases in Analysis of Time of Infusion: NCI/SWOG Trial S1404 Among Participants With High-Risk Resectable Melanoma Who Received Adjuvant Anti-PD-1 Therapy. โ Othus Megan et al., JCO Oncol Pract
A total of 628 participants received pembrolizumab and had time of first infusion recorded. The optimal cut point for first infusion time for OS was 15:48 with hazard ratio (HR) = 1.40; changing the cut point by 30 minutes earlier to 15:18 decreased HR to 0.98, indicating lack of robustness of the threshold.
Clinical bottom line: Bias-corrected analysis of adjuvant pembrolizumab found no significant association between time of day of infusion and recurrence-free or overall survival.
Pregnancy Outcomes After in Utero Exposure to Immune Checkpoint Inhibitors. โ Bou Zerdan Morgan et al., Curr Oncol
The literature review identified 21 reported pregnancies with ICI exposure and variable outcomes. Most resulted in live births (85.7%), though preterm delivery occurred in approximately 50% of cases, often due to maternal or fetal indications.
Clinical bottom line: In utero ICI exposure often results in live births but may carry increased maternal and fetal risk, reinforcing the importance of contraception during therapy.
Personalized targeting of BCL2 family proteins overcomes acquired resistance to BRAF-MEK inhibitors in preclinical melanoma. โ Y N Vashisht Gopal et al., Nat Commun
Combining BCL2 inhibitors (navitoclax or venetoclax) with BRAFi+MEKi induces tumor regressions in a subset of resistant patient-derived xenografts. High basal BCL2 predicts response whereas high basal MCL1 predicts resistance to this strategy.
Clinical bottom line: Personalized BCL2-family inhibition combined with BRAF-MEK inhibition reverses acquired resistance in preclinical melanoma models with BCL2/MCL1 as predictive biomarkers.
๐ฃ๏ธ 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).
Update: Nature Medicine retracts the immunotherapy infusion-timing study, removing the only prospective time-of-day evidence
The article claiming that early morning immunotherapy works better than in the afternoon has been retracted, removing the only prospective evidence that time-of-day matters for checkpoint therapy outcomes. A bias-corrected analysis of 628 pembrolizumab recipients from NCI/SWOG Trial S1404 found no significant association between infusion time and outcomes, with an optimal OS cut point at 15:48 (HR 1.40) that fell to HR 0.98 when the threshold was shifted by just 30 minutes. With the prospective infusion-timing study retracted and a bias-corrected adjuvant analysis null, the question for clinicians is whether time-of-day scheduling should be abandoned entirely.
Discussed by: @JaniceTNBCmets, @PTarantinoMD
Liquid EcoTyper infers spatial tumor ecotypes from cfDNA methylation tied to immunotherapy benefit in melanoma
Zhang et al. introduced Liquid EcoTyper, which infers spatial tumor ecotypes from cfDNA methylation associated with immunotherapy benefit in melanoma. The inferred ecotypes outperformed cfDNA burden, TMB, and PD-L1 as predictors of outcome. Specialists are weighing whether a cfDNA methylation-based readout of tumor spatial organization can replace TMB and PD-L1 for immunotherapy selection.
Discussed by: @EladSharonMD, @EytanRuppin
Gut microbiome associated with recurrence-free survival in resected high-risk melanoma on adjuvant immunotherapy
A publication in Cell reported that gut microbiome composition is associated with recurrence-free survival in patients with resected high-risk melanoma receiving adjuvant immune checkpoint blockade. Oncologists are debating whether gut microbiome profiling could stratify recurrence risk in this patient population.
Discussed by: @VivekSubbiah, @OncoAlert
Update: FDA accepts third RP1 plus nivolumab BLA resubmission with priority review and August 2 PDUFA date
The FDA accepted the resubmission of the Biologics License Application for RP1 (vusolimogene oderparepvec) in combination with nivolumab (Opdivo) for the treatment of advanced melanoma, with a commitment to an accelerated review for approval. This is the third BLA resubmission for the combination; the agency has prioritized its review and set a PDUFA date of August 2nd. Clinicians are watching whether this date will deliver the first approved oncolytic immunotherapy for anti-PD-1 refractory melanoma.
Discussed by: @CureMelanoma, @Melanoma_doctor
Imneskibart Phase 2 data in checkpoint-refractory metastatic melanoma at ASCO26
Phase 2 data for imneskibart in doublet checkpoint inhibitor-refractory metastatic melanoma were presented at ASCO26, showing a 33% objective response rate (ORR) and 67% disease control rate (DCR). Specialists are debating whether an IL-2 redirecting antibody offers a meaningful option for patients who have progressed on doublet checkpoint therapy.
Discussed by: @AulosBioscience, @BiotechTV
๐ฅ Top Ranked Tweets
CancerNetworkยฎ @CancerNetwrk
45-mg binimetinib tablets received tentative approval from the FDA for its ANDA to be used with encorafenib in BRAF V600E or V600K+ unresectable or metastatic melanoma, or for NSCLC with a BRAF V600E mutations.
https://t.co/v5U0CEBfXQ
#melsm #lcsm #NSCLC #oncology https://t.co/6X7O4Pbbf3
๐ 1 โค๏ธ 0 ๐ 0 ๐ 187
Melanoma Research Foundation @CureMelanoma
#MelanomaTreatmentUpdate โ Today, the @US_FDA accepted the resubmission of the Biologics License Application (BLA) for RP1 (vusolimogene oderparepvec) in combination with nivolumab (Opdivo) for the treatment of advanced melanoma. With a commitment to an accelerated review for approval, this announcement underscores immense hope for patients with anti-PD1 refractory metastatic melanoma who do not find success with other FDA approved therapeutics or clinical trials.
The treatment sponsor expects a response goal date of August 2. Enrollments are ongoing for the IGNYTE-3 study for advanced melanoma patients and the REVEAL trial which evaluates RP2 + nivolumab in metastatic uveal melanoma patients.
For more information, visit - https://t.co/Il0FZV7DsN
๐ 2 โค๏ธ 3 ๐ 1 ๐ 335
Elad Sharon @EladSharonMD
RT @EytanRuppin: Can a blood test read the spatial organization of a tumor?
In a recent @Nature study, Zhang et al. (@Wubing44589261, @AaronNewmanLab) introduced Liquid EcoTyper, which infers spatial tumor ecotypes from cfDNA methylation, associated with immunotherapy benefit in melanoma. ๐งต1/4 https://t.co/1AqeUXQfGG
๐ 61 โค๏ธ 92 ๐ 25 ๐ 8,215
Vivek Subbiah, MD @VivekSubbiah
Gut microbiome is associated with recurrence-free survival in patients with resected high-risk melanoma receiving adjuvant immune checkpoint blockade: Cell https://t.co/o1ci95LCTJ
๐ 12 โค๏ธ 19 ๐ 6 ๐ 1,719
Society for Immunotherapy of Cancer @sitcancer
RT @jitcancer: New #JITC article: "Melanoma cell states shape spatial tumor-immune ecosystems to dictate the efficacy of anti-PD1 immunotherapy" https://t.co/LlvquQKRjf
@CARAMELJulie1 https://t.co/JecMkWvnPR
๐ 9 โค๏ธ 45 ๐ 19 ๐ 3,174
European Society of Pathology (ESP) @ESP_Pathology
๐ฌ Complete regression of melanoma liver metastases after #immunotherapy!
๐กA visualy striking example of how modern treatments can transform disease!
Dr Rui Caetano Oliveira, University of Coimbra, Portugal. #ESPAlumni
#EveryDayPathology
#PathX #PathTwitter https://t.co/TwdTHIxw4Y
๐ 1 โค๏ธ 16 ๐ 4 ๐ 536
OncoAlert @OncoAlert
RT @Sarbaji85064063: As cancer immunotherapy moves beyond PD-1/PD-L1 and CTLA-4, we must recognize that each new immune target may have its own toxicity fingerprint.
Kudos to @waraonc23 on publishing this important systematic review and meta-analysis in JNCI Cancer Spectrum.
Across 27 trials and 3,946 patients, the key findings were:
โข LAG-3โdirected therapy was associated with increased adrenal insufficiency, and arthralgia.
โข TIGIT blockade was associated with increased rash, without a significant increase in severe adverse events.
โข Pooled analyses identified additional toxicity signals: pneumonitis and hepatitis with TIM-3, rash with CD40 agonists, and diarrhea with OX40 agonists.
The key message for clinicians and drug developers: emerging checkpoints should not be assumed to share the safety profile of established immunotherapies. Target-specific monitoring must become part of trial design and clinical implementation.
Congratulations, Fuji, @MrinaliniR57669 and to our entire collaborative team!
@BrainTumorDoc @BaptistHealthSF @BHAcademics @MiamiCancerInst @RoswellPark @RoswellHemOnc @UBIMResidency @OncBrothers @OncoAlert @OncUpdates @OxUniPress
https://t.co/rJYZtIxcha
๐ 1 โค๏ธ 11 ๐ 7 ๐ 1,976
OncoAlert @OncoAlert
RT @JournalCancer: ๐งฌ A new #CancerScope covers findings published in The Lancet Oncology showing no recurrence-free survival benefit from adding vibostolimab to pembrolizumab in high-risk melanoma.
Section Editor Dr. @diwakardavar discusses the lessons learned:
https://t.co/xUyW973SiW
@OncoAlert https://t.co/TpSC24150Z
๐ 0 โค๏ธ 5 ๐ 7 ๐ 652
Eric D Whitman, MD @Melanoma_doctor
Excellent next step
[Quoting @Replimune: Today, we announced that the FDA has accepted our resubmission of the RP1 BLA for the treatment of advanced melanoma.
Read more: https://t.co/xTyZoWpNhY https://t.co/KqV7fsmQph]
๐ 0 โค๏ธ 4 ๐ 1 ๐ 1,296
OncoAlert @OncoAlert
RT @CACancerJournal: ๐ Our latest Perspectives: Research in Context covers the final analysis of the CheckMate 238 trial. Results support a sustained finding of longer recurrence-free survival with nivolumab than with ipilimumab for stage III or IV #melanoma.
https://t.co/7hEc5gqjTl
@OncoAlert https://t.co/frOhUiBNWh
๐ 0 โค๏ธ 2 ๐ 2 ๐ 515
OncLive.com @OncLive
๐ฐโAs a surgeon, I believe strongly that these patients should get a surgical opinion early, because one of the first branch points is to sort out if they are resectable or not," said Neil D. Gross, MD of @UTMDAnderson on how antiโPD-1 therapy is changing treatment approaches in advanced CSCC.
Read more here โก๏ธ: https://t.co/fAJ8U2ZuFm
#oncology
๐ 0 โค๏ธ 2 ๐ 1 ๐ 710
DermImmunoTherapy.com @dermimmuno.bsky.social
At #ASCO26, Katharina Kรคhler, of @uni-kiel.de, discussed results from the PIVOTAL trial, which looked at the intralesional agent #daromun for #melanoma.
๐น Watch the full interview:
www.docwirenews.com/post/daromun...
๐ 0 โค๏ธ 1 ๐ 0 ๐ 0
OncLive.com @OncLive
The @FDAOncology has accepted the third BLA resubmission for vusolimogene oderparepvec (RP1) plus nivolumab in advanced melanoma, marking another key regulatory milestone for the investigational oncolytic immunotherapy.
The agency will prioritize its review and has set an PDUFA date of August 2nd.๐๏ธ
Read more about the latest update and what it means for the program โฌ๏ธ #melsm #Oncology
https://t.co/GvLf3Rj7pg
#melanoma #oncology
๐ 0 โค๏ธ 1 ๐ 0 ๐ 428
Aulos Bioscience @AulosBioscience
At #ASCO26, CEO Aron Knickerbocker joined @BiotechTV to discuss our new Phase 2 data for imneskibart in doublet checkpoint inhibitor-refractory metastatic melanoma, including a 33% objective response rate (ORR) and 67% disease control rate (DCR).
Aron walks through the positive results from the cohorts evaluating imneskibart and low-dose, subcutaneous aldesleukin with and without a checkpoint inhibitor (nivolumab), and outlines the next steps in our clinical development path.
#CancerResearch #Immunotherapy
[Quoting @BiotechTV: ๐๐๐๐ ๐๐๐๐: @AulosBioscience presented updated phase 2 data in checkpoint inhibitor-refractory metastatic melanoma for its IL-2 redirecting antibody, imneskibart. #ASCO26
Full video: https://t.co/6dCpG3OzhD https://t.co/sXCpaDdvYa]
๐ 0 โค๏ธ 0 ๐ 0 ๐ 22
Prepared by Rafael Santana-Davila, M.D. Questions or feedback? Just reply to this email.
Disclaimer: This digest is AI-generated. Content may contain errors -- always verify with original sources.
Know a colleague who would find this useful? Forward this email or have them subscribe here.
If you find this useful, ☕ buy me a coffee.