Melanoma & Cutaneous Oncology Research Updates

In tumor-bearing mouse models (established melanoma and additional colorectal and triple-negative breast cancer models), a single dose of cyclophosphamide given one day before combined anti–PD-1 and anti–CTLA-4 immune checkpoint blockade delayed tumor progression and prolonged survival compared with ICB alone. The enhanced antitumor effect—also observed when other lymphodepleting treatments such as gemcitabine or radiation were used—was driven primarily by clonal expansion of activated/effector CD8+ tumor-infiltrating lymphocytes.

This first‑in‑human phase 1 study tested lomvastomig, an Fc‑silenced PD‑1–TIM‑3 bispecific antibody, in patients with advanced/metastatic solid tumors (39 in dose‑escalation, 95 in expansion across CPI‑experienced melanoma/NSCLC and CPI‑naïve SCLC/ESCC cohorts). Lomvastomig was tolerable up to 2,100 mg Q2W (one DLT of grade 3 troponin T at 1,200 mg; no MTD reached, RDE 2,100 mg), showed linear pharmacokinetics with >90% receptor occupancy at doses ≥70 mg, and produced objective responses at 2,100 mg in dose‑escalation (21%) and in expansion cohorts including CPI‑experienced melanoma (8%) and CPI‑naïve ESCC (20%), with limited activity in CPI‑experienced melanoma and NSCLC but an encouraging signal in CPI‑naïve ESCC.

This meta-analysis of patients with metastatic uveal melanoma compared percutaneous hepatic perfusion (PHP) (n=455) with best alternative care (BAC) (n=125) across 11 studies. PHP was associated with substantially higher overall response rate (47.4% vs 6.0%) and longer progression-free survival (pooled 1‑year PFS 30.1% vs 6.4%; median PFS 7.7 vs 2.6 months), but pooled overall survival differences were modest (median OS 17.3 vs 14.0 months) and did not demonstrate a clear survival benefit; hematologic toxicities were the most reported adverse events.