Combined Targeting of PD-1 and TIM-3 in Patients with Locally Advanced or Metastatic Melanoma: AMBER Cohorts 1c, 1e, and 2A

Abstract

PURPOSE: The phase I, open-label, multicenter AMBER study (NCT02817633) is evaluating cobolimab, an anti-T-cell immunoglobulin and mucin-domain containing protein-3 humanized mAb, as a monotherapy and combination therapy in patients with solid tumors. In this study, the safety and efficacy of cobolimab plus dostarlimab, a PD-1 inhibitor, in patients with locally advanced/metastatic melanoma who were either immunotherapy-naïve or had progressed on prior anti-PD-(L)1 therapy, are reported. PATIENTS AND METHODS: Adults with adequate organ function and either immunotherapy-naïve (parts 1c/1e) or anti-PD-(L)1 relapsed or refractory (part 2A) melanoma were enrolled and received cobolimab 100, 300, or 900 mg and dostarlimab 500 mg every 3 weeks. Treatment continued until disease progression, unacceptable toxicity, withdrawal of consent, or death (whichever occurred sooner). Endpoints included safety, tolerability, overall response rate, and disease control rate. RESULTS: The current integrated analysis included 28 patients who received treatment in parts 1c/1e and 43 patients who received treatment in part 2A. Treatment-related serious adverse events were observed in 14.3% and 9.3% of patients in parts 1c/1e and 2A, respectively. The overall response rate (95% confidence interval) was 42.9% (24.5-62.8) and 4.7% (0.6-15.8) for patients in parts 1c/1e and 2A, respectively, and the disease control rate (95% confidence interval) was 53.6% (33.9-72.5; 1c/1e) and 20.9% (10.0-36.0; 2A). CONCLUSIONS: In this exploratory setting, cobolimab plus dostarlimab was well tolerated, with reported preliminary efficacy similar to other anti-T-cell immunoglobulin and mucin-domain containing protein-3 treatments in patients with locally advanced/metastatic melanoma. See related article by Davar et al., p. 3443.

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