📬 Melanoma Intelligence Digest — Week 2026-W30
A biology-matched antibody-drug conjugate showed activity in GNAQ/GNA11-mutant uveal melanoma, a Swedish cohort validated neoadjuvant immunotherapy in routine practice, and a bias-corrected SWOG S1404 analysis overturned the immunotherapy infusion-timing hypothesis.
⚡ TL;DR
📄 Publications
- An anti-PMEL antibody-drug conjugate with a Gq/11 inhibitor payload in GNAQ/GNA11-mutant melanomas: a phase 1 trial. — Objective responses were seen in 13 out of 66 patients (19.7%) and tumor reduction in 47 out of 66 patients (71.2%)
- Neoadjuvant immunotherapy for resectable cutaneous melanoma: a nationwide population-based cohort. — Nationwide cohort of 279 consecutive patients with resectable stage III-IV cutaneous melanoma treated with neoadjuvant ICI in Sweden
🐦 Twitter / 🦋 Bluesky
- Long-term survivors after anti-PD-1 in advanced melanoma show early rise in 4-1BB+ CD4 T cells — In long-term survivors after anti-PD-1 in advanced melanoma (n=58), baseline CD4/CD8 T-cell subsets did not differ by survival, but long-term survivors showed an early increase in 4-1BB+ CD4 T cells during treatment
- Jedd Wolchok traces melanoma immunotherapy arc toward realistic 10-year survival in stage IV — Wolchok's career arc has resulted in 10-year survival being a realistic goal in stage IV melanoma
- Pathway-targeted therapy expands options for NRAS-driven melanoma in preclinical work — Research led by Martin McMahon and Mona Foth could help expand future treatment options for people with advanced NRAS-driven melanoma
Full details below ↓
📄 What's Being Published
An anti-PMEL antibody-drug conjugate with a Gq/11 inhibitor payload in GNAQ/GNA11-mutant melanomas: a phase 1 trial. — Carlino Matteo S et al., Nat Med
In this phase 1 trial, objective responses were seen in 13 out of 66 patients (19.7%) and tumor reduction in 47 out of 66 patients (71.2%). Median progression-free survival was 7.2 (95% CI: 5.3–7.8) months. Grade 3 treatment-related adverse events occurred in five patients (7.6%), including one dose-limiting toxicity of grade 3 hypotension.
Clinical bottom line: DYP688, a PMEL-directed antibody-drug conjugate delivering a Gq/11 inhibitor payload, was well tolerated and produced a 19.7% objective response rate in GNAQ/GNA11-mutant uveal melanoma, an area with few options.
Neoadjuvant immunotherapy for resectable cutaneous melanoma: a nationwide population-based cohort. — Nelson Axel et al., J Natl Cancer Inst
This nationwide, population-based cohort study included 279 consecutive patients with resectable stage III–IV cutaneous melanoma treated with neoadjuvant ICI in Sweden. Major pathological response occurred in 43%, including 37% with complete response. After a median follow-up of 20 months, estimated 24-month EFS was 69%, DMFS 75%, and OS 87%.
Clinical bottom line: In a nationwide Swedish cohort, neoadjuvant PD-1 inhibitor therapy reproduced randomized-trial outcomes in routine practice, but withholding adjuvant therapy after major pathological response was associated with recurrence.
🗣️ 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).
Long-term survivors after anti-PD-1 in advanced melanoma show early rise in 4-1BB+ CD4 T cells
In a cohort of long-term survivors after anti-PD-1 therapy in advanced melanoma (n=58), baseline CD4/CD8 T-cell subsets did not differ by survival status; however, long-term survivors showed an early increase in 4-1BB+ CD4 T cells during treatment. This early rise was associated with increased LAG3+TIM3+ CD4 T cells and later reduced FOXP3+ CD4 T cells. The central debate is whether on-treatment immune dynamics, rather than baseline T-cell subsets, better identify patients who achieve durable responses to anti-PD-1.
Discussed by: @OncoAlert, @MarioBalsaMD
Jedd Wolchok traces melanoma immunotherapy arc toward realistic 10-year survival in stage IV
Jedd Wolchok offered a tour of melanoma immunotherapy spanning the tyrosinase vaccine through CTLA-4, PD-1, TILs, CARs, and TCRs, and described a soon-to-be-published paper in Cancer Research on lymphodepletion as an IO sensitizing strategy. Clinicians noted the arc of this work has resulted in 10-year survival becoming a realistic goal in stage IV melanoma. The open question is how close the field now is to making that outcome a routine expectation rather than an exceptional one.
Discussed by: @DrBetofMDPhD, @FunchainMD, @StanfordCancer
Pathway-targeted therapy expands options for NRAS-driven melanoma in preclinical work
A research team from Huntsman Cancer Institute at the University of Utah, led by Martin McMahon and Mona Foth, reported preclinical findings on a pathway-targeted therapy as a potential treatment for advanced NRAS-driven melanoma. The work was described as a step toward expanding treatment options for a patient population with limited targeted-therapy choices. Specialists are weighing whether pathway-targeted approaches such as daraxonrasib can fill the gap for NRAS-mutant melanoma following progression on immunotherapy.
Discussed by: @EladSharonMD, @OncLive, @Cancer_Buzz
🔥 Top Ranked Tweets
Dr. Patrick Hwu @PatrickHwuMD
🧬 #ScienceSaturday
❓ What if cancer treatment decisions could be guided not only by the tumor cells themselves, but by the ecosystem around them?
➡️ A new study in @Nature introduces a machine-learning approach to study the tumor microenvironment, or the “neighborhood” around tumor cells made up of immune cells, blood vessel cells, fibroblasts and other supporting cells.
➡️ Researchers analyzed more than 10 million single-cell and spatial transcriptomic profiles across multiple cancer types to understand not only which cells are present in tumors, but where they are located and how they interact.
➡️ They identified nine recurring “spatial ecotypes,” or tumor neighborhoods, each with distinct biology and location patterns. Some were found near the tumor core, others at the tumor edge or surrounding tissue.
➡️ Importantly, some of these tumor neighborhoods were linked to patient outcomes and response to immune checkpoint inhibitors, a type of immunotherapy that helps the immune system recognize and attack cancer.
➡️ The most exciting part: the team showed that these spatial patterns could also be detected using cell-free DNA from blood samples, offering a potential non-invasive way to better understand the tumor microenvironment.
➡️ In patients with melanoma, these blood-based signals were strongly associated with response to immunotherapy, suggesting this approach could one day help guide treatment decisions.
💡 The takeaway: tumors are more than just cancer cells. Their surrounding ecosystem plays a major role in how cancer grows, hides and responds to treatment. This study points to a future where liquid biopsies may help us read that ecosystem in real time, bringing us closer to more personalized cancer care.
@AaronNewmanLab @Stanford @czbiohub @MayoClinic @Yale @rondell_graham @YaleGenetics @YaleCancer @SmilowCancer @StanfordCancer @Columbia @columbiacancer @columbiamed @MedicalCollege @Oslounivsykehus @WashUMedicine @UniOslo @WilmotCancer
Read more: https://t.co/OOwjAAFtzm
🔖 57 ❤️ 78 🔁 25 👁 7,083
OncoAlert @OncoAlert
RT @MarioBalsaMD: 🤔 Long-term survivors after anti–PD-1 in advanced melanoma (n=58)! What about 4-1BB⁺ CD4 T cells?
https://t.co/KVhlKD6dzv
▪️Baseline CD4/CD8 T-cell subsets did not differ by survival
💥 Long-term survivors showed an early increase in 4-1BB⁺ CD4 T cells during treatment
🎯 This was associated with increased LAG3⁺TIM3⁺ CD4 T cells and later reduced FOXP3⁺ CD4 T cells
🩸 On-treatment immune dynamics, rather than baseline, may better identify durable responders
@OncoAlert
@OncoReporte @myESMO @_SEOM
🔖 12 ❤️ 23 🔁 7 👁 2,013
OncoAlert @OncoAlert
RT @OncoAlert: 🕒 Does the time of day of immunotherapy matter?
It is NOW time for This #WeekInOncology by @OncoAlert 🚨, this time with our AF colleague @MarioBalsaMD 🇪🇸Discussing the latest in #Melanoma
A multicenter analysis of 628 patients with high-risk #melanoma treated with adjuvant #Pembrolizumab found no significant association between infusion timing and recurrence-free or overall survival after accounting for important sources of bias.
These findings challenge previous reports suggesting earlier immunotherapy infusions improve outcomes and highlight the importance of rigorous statistical methodology in interpreting timing-related treatment effects.
JCO OP Publication👇being discussed:
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
https://t.co/8vj4fyzaLS
@EladSharonMD
@KenGrossmannMD
@jmkirkwood
@VernSondakMD
@DrSapnaPatel
@mihalcioiui
Pinging #OncoAlertAF Faculty
@nataliagandur
@realbowtiedoc
@FernandoOnco
@ElisaAgostinett
@to_be_elizabeth
@MarioBalsaMD
@BRicciutiMD
@HHorinouchi
@UOzkerim
@p_ciracimd
@AmandaNizamMD
@scocmem
@DrVilmaPBarcia
@DraMartinezLago
@DrMirallas
@GIMedOnc
@BettinaRyll
@DrBetofMDPhD
pinging @FunchainMD @CureMelanoma @Melanoma_doctor @HTawbi_MDPhD @Chrystal_Paulos @JaniceM10 @ProfGLongMIA @ProfRAScolyer
@JeffGershenwald @MelanomaAus @AIMatMelanoma
🔖 3 ❤️ 20 🔁 6 👁 6,850
OncoAlert @OncoAlert
🕒 Does the time of day of immunotherapy matter?
It is NOW time for This #WeekInOncology by @OncoAlert 🚨, this time with our AF colleague @MarioBalsaMD 🇪🇸Discussing the latest in #Melanoma
A multicenter analysis of 628 patients with high-risk #melanoma treated with adjuvant #Pembrolizumab found no significant association between infusion timing and recurrence-free or overall survival after accounting for important sources of bias.
These findings challenge previous reports suggesting earlier immunotherapy infusions improve outcomes and highlight the importance of rigorous statistical methodology in interpreting timing-related treatment effects.
JCO OP Publication👇being discussed:
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
https://t.co/8vj4fyzaLS
@EladSharonMD
@KenGrossmannMD
@jmkirkwood
@VernSondakMD
@DrSapnaPatel
@mihalcioiui
Pinging #OncoAlertAF Faculty
@nataliagandur
@realbowtiedoc
@FernandoOnco
@ElisaAgostinett
@to_be_elizabeth
@MarioBalsaMD
@BRicciutiMD
@HHorinouchi
@UOzkerim
@p_ciracimd
@AmandaNizamMD
@scocmem
@DrVilmaPBarcia
@DraMartinezLago
@DrMirallas
@GIMedOnc
@BettinaRyll
@DrBetofMDPhD
pinging @FunchainMD @CureMelanoma @Melanoma_doctor @HTawbi_MDPhD @Chrystal_Paulos @JaniceM10 @ProfGLongMIA @ProfRAScolyer
@JeffGershenwald @MelanomaAus @AIMatMelanoma
🔖 3 ❤️ 19 🔁 6 👁 6,664
OncoAlert @OncoAlert
RT @MarioBalsaMD: 📄 Surgical feasibility and outcomes following neoadjuvant ICI before surgery in resectable stage III/IV melanoma (Systematic review & meta-analysis, 20 studies, n=1,384)
https://t.co/bt4k1TaH03
🎯 pCR 33% | MPR 46% | Overall pathological response 59%
🔴 Failure/delay to surgery: 9%
⚠️ Major surgical complications: 8%
💥 Lower recurrence risk vs adjuvant approaches
@OncoAlert
@OncoReporte @myESMO @_SEOM
🔖 3 ❤️ 9 🔁 7 👁 808
OncoAlert @OncoAlert
RT @MarioBalsaMD: Does timing matter? Maybe.
Does methodology matter? Absolutely!
Happy to discuss this elegant SWOG S1404 analysis showing how rigorous statistics can overturn an appealing clinical hypothesis 💥
If you’re interested in melanoma, adjuvant immunotherapy, and why bias matters, I hope you enjoy this week’s #WeekInOncology with @OncoAlert 🧡
@hospitalclinic @myESMO @_SEOM
🔖 1 ❤️ 15 🔁 6 👁 9,153
PeerView @PeerView
Melanoma immunotherapy continues to evolve. Hear Geoffrey T. Gibney, MD, and Meredith McKean, MD, MPH (@MeredithMcKean), discuss the latest evidence across resectable and metastatic disease: https://t.co/sI37NNZyQ2
#ASCO26 #Melanoma #CME #MedEd
🔖 1 ❤️ 4 🔁 2 👁 157
Targeted Oncology @TargetedOnc
🔬 Tucidinostat plus nivolumab extends PFS in treatment-naive advanced #melanoma, offering a promising oral, chemo-free boost to frontline immunotherapy.
The treatment demonstrated a 58% improvement in PFS.
Read more: https://t.co/1A4UYHRCUw
#SkinCancer #Oncology
🔖 1 ❤️ 0 🔁 0 👁 246
Elad Sharon @EladSharonMD
RT @nataliagandur: ⏰ Does the timing of immunotherapy really matter?
This week's #WeekInOncology by @OncoAlert 🚨 features an outstanding review by our AF colleague @MarioBalsaMD 🇪🇸, who breaks down the latest evidence in #Melanoma with his trademark clarity and clinical insight.
📄 Discussing the JCO OP analysis of the NCI/SWOG S1404 trial:
A multicenter study of 628 patients receiving adjuvant #Pembrolizumab found no significant association between infusion timing and recurrence-free or overall survival after rigorous adjustment for time-related biases.
💡 An important reminder that robust methodology is just as critical as the clinical question itself—and that not every appealing hypothesis withstands careful analysis.
📖 JCO OP:
https://t.co/GzSkN3zG0P…
👏 Excellent summary by @MarioBalsaMD!!
@EladSharonMD @KenGrossmannMD @jmkirkwood @VernSondakMD @DrSapnaPatel @mihalcioiui
#WeekInOncology #OncoAlert #Immunotherapy #SkinCancer #ClinicalResearch
🔖 0 ❤️ 7 🔁 3 👁 696
Dra. María Natalia Gandur Quiroga @nataliagandur
⏰ Does the timing of immunotherapy really matter?
This week's #WeekInOncology by @OncoAlert 🚨 features an outstanding review by our AF colleague @MarioBalsaMD 🇪🇸, who breaks down the latest evidence in #Melanoma with his trademark clarity and clinical insight.
📄 Discussing the JCO OP analysis of the NCI/SWOG S1404 trial:
A multicenter study of 628 patients receiving adjuvant #Pembrolizumab found no significant association between infusion timing and recurrence-free or overall survival after rigorous adjustment for time-related biases.
💡 An important reminder that robust methodology is just as critical as the clinical question itself—and that not every appealing hypothesis withstands careful analysis.
📖 JCO OP:
https://t.co/GzSkN3zG0P…
👏 Excellent summary by @MarioBalsaMD!!
@EladSharonMD @KenGrossmannMD @jmkirkwood @VernSondakMD @DrSapnaPatel @mihalcioiui
#WeekInOncology #OncoAlert #Immunotherapy #SkinCancer #ClinicalResearch
[Quoting @OncoAlert: 🕒 Does the time of day of immunotherapy matter?
It is NOW time for This #WeekInOncology by @OncoAlert 🚨, this time with our AF colleague @MarioBalsaMD 🇪🇸Discussing the latest in #Melanoma
A multicenter analysis of 628 patients with high-risk #melanoma treated with adjuvant #Pembrolizumab found no significant association between infusion timing and recurrence-free or overall survival after accounting for important sources of bias.
These findings challenge previous reports suggesting earlier immunotherapy infusions improve outcomes and highlight the importance of rigorous statistical methodology in interpreting timing-related treatment effects.
JCO OP Publication👇being discussed:
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
https://t.co/8vj4fyzaLS
@EladSharonMD
@KenGrossmannMD
@jmkirkwood
@VernSondakMD
@DrSapnaPatel
@mihalcioiui
Pinging #OncoAlertAF Faculty
@nataliagandur
@realbowtiedoc
@FernandoOnco
@ElisaAgostinett
@to_be_elizabeth
@MarioBalsaMD
@BRicciutiMD
@HHorinouchi
@UOzkerim
@p_ciracimd
@AmandaNizamMD
@scocmem
@DrVilmaPBarcia
@DraMartinezLago
@DrMirallas
@GIMedOnc
@BettinaRyll
@DrBetofMDPhD
pinging @FunchainMD @CureMelanoma @Melanoma_doctor @HTawbi_MDPhD @Chrystal_Paulos @JaniceM10 @ProfGLongMIA @ProfRAScolyer
@JeffGershenwald @MelanomaAus @AIMatMelanoma]
🔖 0 ❤️ 7 🔁 3 👁 696
OncLive.com @OncLive
🎙️ NEW EPISODE: #OncLiveOnAir: In this episode, @DrNeilGross, of @UTMDAnderson, discusses:
🔑 Key biological differences between CSCC and BCC
🔑 Why resectability is the critical first branch point in treatment planning
🔑 The role of adjuvant cemiplimab
🔑 Toxicity considerations for elderly & immunocompromised patients
🔑 The actively accruing phase 3 NRG-HN014 trial comparing neoadjuvant therapy vs upfront surgery in advanced resectable CSCC
🎧 Listen now: https://t.co/Rsj5XFsznp #Oncology #MedTwitter
🔖 0 ❤️ 3 🔁 1 👁 365
Melanoma Research Foundation @CureMelanoma
Your voice can help shape the future of melanoma treatment. 💙
The FDA is once again reviewing RP1 (vusolimogene oderparepvec) in combination with nivolumab for the treatment of advanced melanoma, with an Advisory Committee meeting scheduled for July 30.
If you are a patient, survivor, caregiver or loved one impacted by advanced melanoma, we encourage you to submit a respectful public comment sharing your experience and why access to new treatment options matters. Personal stories help provide important perspective as the FDA considers this potential therapy.
If you submitted a comment previously, we encourage you to submit again. This review involves a new advisory committee, and current patient experiences are incredibly valuable.
Public comments must be submitted by July 20 at 12:00 PM ET.
Click here to submit your comment: https://t.co/65N1oz4GNm
🔖 0 ❤️ 0 🔁 0 👁 193
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? Just forward them this email.