IO102-IO103 Plus Nivolumab and Relatlimab Demonstrates Encouraging Activity in Unresectable Melanoma
Clinical Summary:
- Design/Population: This multicenter, phase 2 trial evaluated the investigational cancer vaccine IO102-IO103 in combination with nivolumab plus relatlimab in previously untreated patients with unresectable non-uveal melanoma.
- Key Outcomes: The combination met the study's primary end point, achieving a best overall response rate of 60%, including complete responses in 16% of patients. Median duration of response was not reached, and responses were observed regardless of PD-L1 expression. Grade 3/4 treatment-related adverse events occurred in 21% of patients, with no treatment-related deaths.
- Clinical Relevance: These findings suggest that adding IO102-IO103 may enhance antitumor activity without introducing unexpected safety signals, supporting further evaluation as first-line therapy for unresectable melanoma.
Results from a multicenter, phase 2 trial demonstrated that the investigational cancer vaccine IO102-IO103 combined with nivolumab plus relatlimab produced encouraging clinical activity in previously untreated patients with unresectable melanoma.
“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,” stated James William Smithy, MD, Memorial Sloan Kettering Cancer Center, New York, New York, and coauthors. “IO102-IO103 has not yet been assessed in combination with nivolumab [plus] relatlimab.”
In this trial, 43 patients with previously untreated, unresectable non-uveal melanoma received subcutaneous IO102-IO103 administered every 2 weeks for the first 8 weeks and every 4 weeks thereafter with intravenous nivolumab plus relatlimab for up to 2 years. Pre-treatment tissue samples were assessed for PD-L1 protein expression using the 28-8 pharmDx assay. The primary end point was best overall response rate (ORR), as assessed via RECIST version 1.1. Secondary end points included progression-free survival (PFS), duration of response, safety, and exploratory immune biomarker analyses.
At analysis, the best ORR was 60%, including 7 complete responses and 19 partial responses. At a median follow-up of 10.1 months, median duration of response had not been reached, and median PFS was 8.2 months. Among 25 patients with PD-L1-negative tumors, the best ORR was 52% and median PFS was 8.2 months, suggesting activity regardless of baseline PD-L1 expression.
Grade 3/4 treatment-related adverse events occurred in 21% of patients. The most frequently reported adverse events included adrenal insufficiency (n = 2), acute kidney injury (n = 2), aseptic meningitis (n = 1), arthritis (n = 1), maculopapular rash (n = 1), myositis (n = 1), neutropenia (n = 1), and colitis (n = 1). No treatment-related deaths were reported.
Exploratory T-cell receptor sequencing demonstrated on-treatment clonal T-cell expansion in both responders and non-responders compared with baseline, supporting the biologic activity of the combination.
“IO102-IO103 in combination with nivo-rela was associated with a higher [ORR] compared to historical data for nivo-rela alone, meeting the trial’s primary end point,” concluded Dr Smithy et al. “These findings support the further clinical investigation of IO102-IO103 with nivo-rela as an initial treatment for unresectable melanoma.”
Source:
Smithy JW, Kalvin HL, Thimar JR, et al. A phase 2 trial of IO102-IO103 and nivolumab-relatlimab in previously untreated, unresectable melanoma. Presented at the ASCO Annual Meeting; May 30–June 3, 2025; Chicago, Illinois. Abstract 9519.
