Marco Donia, Professor at University of Copenhagen (Københavns Universitet), shared Yago Garitaonaindia’s, Translational Research Fellow at CCIT-DK – National Center for Cancer Immune Therapy of Denmark, post on LinkedIn, adding:
“What to watch: Melanoma at ASCO26
- Novel Cell Therapies in Melanoma
- New combinations for Neoadjuvant Immunotherapy
- Update on Neo-Antigen Vaccines
- Targeted Therapy for Uveal Melanoma
The whole story from the brilliant ASCO featured voice Yago Garitaonaindia.”
Quoting Yago Garitaonaindia’s post:
“ASCO26 guide and how to navigate it: Melanoma edition.
6 abstracts, many open questions, and some context to navigate them.
Disclaimer: this is just my personal view.
1. Cell therapy is back, and this time the toxicity profile looks different
- OBX-115 (engineered TIL with ACZ-inducible membrane-bound IL-15): ORR 67% in 15 patients post-ICI doublet. No high-dose IL-2. Read that line twice. 1/15 CRS G3, no ICANS, no treatment-related deaths.
- Anzu-cel (PRAME TCR-T, n=33): ORR 56%, mOS 16.2 months. CRS G3 18%, CR 1/33. Only 1 new CNS lesion at progression, worth a slide on its own. 16/33 uveal in the cohort, no subtype split published.
Worth comparing toxicity and ICU admissions with the lifileucel trials and Rohaan et al. Too early to talk about efficacy, but the toxicity profile looks really promising (in TIL therapy, early toxicity is what matters). OBX-115 targets one of the most important bottlenecks of TIL therapy: the high-dose IL-2. Two recent reviews in JITC demystify this complex treatment,
Happy to call the old and wise Marco Donia 🧙♂️ to discuss
𝟮. Two neoadjuvant abstracts that only make sense together
- Nivo + Rela + Ipi: pCR 63%, 1 toxic death from myocarditis, encephalitis, 26% G3 irAEs. Toxicity matters, especially in the curative setting.
- Nivo + Rela in stage II: pCR 60% with far fewer G3 events. n=20, so wait for the full dataset. Real unmet need in node-negative disease.
What I’m missing: biomarker-guided selection rather than uniform escalation. New CPI approaches seem to add a different profile of toxicity but not clearly increasing pCR (see MORPHEUS trial, Amaria et al., Long et al.). In this setting, the work by Prof Dr Christian Blank and Minke Lucas around treatment selection is simply superb
𝟯. KEYNOTE-942 at 5 years: intismeran + pembro
RFS benefit sustained at 5 years. No OS signal yet. No new toxicity
The combo is doing what it promised in 2023. INTerpath-001 will settle the regulatory question; the open one is positioning. For those interested in the development, see John Haanen review in Nat Med.
Hypothesis to test in a world of neoadjuvant IO in melanoma, could intensification after non-pCR be the right fit? That is exactly the INTerpath-009 design in NSCLC.
𝟰. Darovasertib + crizotinib in HLA-A2 negative metastatic uveal
Data not available yet, but will this open a new line for a population with a genuine unmet need? Even in HLA-A2+ patients, outcomes need to be improved (see the 5-year tebentafusp survival update).
Happy to be wrong on any of these. That is what discussants are for.
Full Library (worth reading) in the first comment.”
Other articles featuring Marco Donia and Yago Garitaonaindia on OncoDaily.