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

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.

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.

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).

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.