Optimization of immunotherapy duration for advanced melanoma: The prospective OTIMAS trial.

Abstract

1608 Background: Anti-PD1 monotherapy is a common option for first-line treatment for advanced melanoma in resource-constrained settings. A shorter duration of therapy and associated biomarkers of response can reduce financial burden for healthcare systems. Methods: In this phase 2 single-arm trial, pts with unresectable stage III-IV melanoma received pembrolizumab (Pem) 200mg intravenously every 3 weeks for a maximum of 12m. Primary endpoint was 24m progression-free survival (PFS); secondary endpoints included overall response rate per RECIST 1.1 and overall survival (OS) and safety. An additional course of therapy was allowed if progression was observed after 6m of treatment interruption. Exploratory analysis included miRNA cargo of small extracellular vesicles (sEVs) and cost-effectiveness analysis of 12m vs. 24m in the context of the universal Brazilian health system. Results: 29 pts were enrolled from Jan 2022 to Jan 2025. As of Sep 2025, all had completed treatment, with a median follow-up of 19.1m (0.6-45.3). Median age was 59 years (28-85), 55.2% were male, 72.4% had metastatic disease and 20.7% had ECOG-PS >1. 41.4% presented with high baseline LDH. 2 pts had acral melanoma. 20.6% had received previous chemotherapy. Median PFS was 5.7m (IC95% 3.1-8.4) and 24m-PFS, 23.8%. 2-y OS was 42.8% (IC 95% 24.2-61.4). ORR was 34.5% (10/29), with 51.7% DCR. Among 24.1% who completed 12m of Pem, only one pt experienced PD less than 6m after completion of Pem. One death due to immune related pneumonitis was observed. The percentage of variable expressed regions in sEVs differed according to immunotherapy (IO) response profile. Cost analysis showed that the medication cost was reduced by 53.75% when compared to the 2-year strategy. Conclusions: This trial demonstrated that one year treatment with IO is feasible and provides comparable outcomes to a standard 24m treatment (mPFS 5.6 range 3.4–8.2; 2-year OS 55% IC 95% 49-61%), regardless of response. This strategy can be cost effective and provide broader access to immunotherapy and improve resource allocation in public health systems. Specific miRNAs were identified for a potential response signature to select patients with long-term benefit. Clinical trial information: NCT07376317 .