A phase 2 trial of IO102-IO103 and nivolumab-relatlimab in previously untreated, unresectable melanoma.

Abstract

9519 Background: IO102-IO103 is an investigational cancer vaccine that targets both tumor and immune-suppressive cells in the tumor microenvironment. IO102-IO103 has demonstrated clinical activity in combination with anti-PD-1 monotherapy in advanced melanoma, with concordant clonal T cell expansion observed in the tumor and peripheral blood in patients with radiographic response. IO102-IO103 has not yet been assessed in combination with nivolumab-relatlimab (nivo-rela). Methods: In this multicenter, phase 2 trial (NCT05912244) patients with unresectable, previously untreated non-uveal melanoma were treated with subcutaneous IO102-IO103 and intravenous nivo-rela for up to two years. IO102-IO103 was administered every two weeks for eight weeks, and every four weeks thereafter. PD-L1 protein expression was assessed using the 28-8 pharmDx assay on pre-treatment tissue. The primary endpoint was best overall response rate (BORR) by RECIST v1.1, with a plan to reject the null hypothesis based on the proportion of patients with ≥1% membranous PD-L1 staining in the tumor compartment. Secondary endpoints included progression-free survival (PFS), safety assessed by Common Terminology Criteria for Adverse Events v 5.0, and duration of response (DOR). PFS and DOR were summarized using Kaplan-Meier methods. Bulk T cell receptor (TCR) sequencing was performed on peripheral blood mononuclear cells using an RNA-based assay at baseline, week 4 and week 8. Results: Among 43 evaluable patients, the BORR was 60% (95% confidence interval [CI]: 44-75%), including 19 patients with partial response and 7 patients with complete response. At database lock (Dec 1 2025), median follow up was 10.1 months (interquartile range 6.1-19.3). The median duration of response was not reached (95% CI: 14, NR) and median PFS was 8.2 months (95% CI 6.8, not reached [NR]). Among patients with PD-L1 negative tumors (n = 25), the BORR was 52% (95% CI 31-72%) and median PFS was 8.2 months (4.2, NR). Grade 3-4 treatment-related adverse events occurred in 9 patients (21%), including adrenal insufficiency (2 patients), acute kidney injury (2), aseptic meningitis (1), arthritis (1), maculopapular rash (1), myositis (1), neutropenia (1), and colitis (1). There were no treatment related deaths. T cell clonal expansion was observed at on-treatment time points compared to baseline in patients with and without radiographic response. Conclusions: IO102-IO103 in combination with nivo-rela was associated with a higher objective response rate compared to historical data for nivo-rela alone, meeting the trial’s primary endpoint. No unexpected safety signals were observed. These findings support the further clinical investigation of IO102-IO103 with nivo-rela as an initial treatment for unresectable melanoma. Clinical trial information: NCT05912244 .