AMBER parts 1c and 1e: A phase 1 study of cobolimab plus dostarlimab in patients (pts) with advanced/metastatic melanoma.

Abstract

9513 Background: TIM-3 and PD-1 are markers of T-cell suppression that are upregulated in melanoma. AMBER (NCT02817633) is evaluating cobolimab (TSR-022/GSK4069889), an anti-TIM-3 therapy, monotherapy or with PD-1 inhibitors, including dostarlimab, in pts with solid tumors. Methods: This multicenter, open-label study was conducted in 2 parts: dose escalation (Parts 1 A–D and F–H) and cohort expansion (Parts 2 A–D). Part 1C and exploratory cohort 1E (reported here) included pts with advanced/metastatic melanoma; prior therapies, except for immunotherapies, were permitted. Pts received cobolimab (100 [1C only], 300, or 900 mg IV) with dostarlimab (500 mg IV) Q3W. Part 1C primary endpoints were safety, tolerability, and recommended Phase 2 dose. Objective response rate (ORR; complete [CR] or partial [PR] response per RECIST v1.1) was a secondary endpoint in 1C and the primary endpoint in 1E (ad hoc efficacy analysis reported). An integrated safety analysis for all pts (Parts 1 and 2) receiving cobolimab with dostarlimab, regardless of tumor type or cobolimab dose, is reported here. Results: 28 pts were enrolled in 1C (n=10) and 1E (n=18). Most pts (n=23; 82.1%) had cutaneous disease of the skin. One pt had anorectal mucosal disease and 3 pts in the 900-mg cohort had uveal melanoma. Most pts (67.9%) had an ECOG PS=0. At data cut-off (May 19, 2021), treatment was ongoing in 5 pts. In the integrated safety analysis of pts who received cobolimab 100 mg (n=41), 300 mg (n=167), or 900 mg (n=69) with dostarlimab, treatment-related treatment-emergent AEs (TR-TEAEs) occurred in 53.7%, 57.5%, and 59.4%, respectively. The most common TR-TEAEs (any grade, ≥10% in 100 mg, 300 mg, or 900 mg groups, respectively) were fatigue (22.0%, 13.2%, 24.6%), rash (9.8%, 5.4%, 11.6%), diarrhea (4.9%, 6.0%, 10.1%), and dyspnea (2.4%, 0%, 10.1%). Grade ≥3 TR-TEAEs occurred in 12.2% (100 mg), 10.8% (300 mg), and 20.3% (900 mg); serious TR-TEAEs occurred in 7.3%, 7.8%, and 11.6%, respectively. No pts died due to TR-TEAEs; 2.4% (100 mg), 4.2% (300 mg), and 7.2% (900 mg) discontinued due to TR-TEAEs. ORR and disease control rate (DCR: stable disease [SD] ≥16 weeks, PR, or CR) are shown in the Table. Twelve pts achieved a PR and an immune-related (ir)PR (1 in 100 mg; 8 in 300 mg; 3 in 900 mg groups). Three pts achieved SD (2 in 300 mg; 1 in 900 mg groups); 8 pts had irSD (1 in 100 mg; 4 in 300 mg; 3 in 900 mg groups). Conclusions: Cobolimab with dostarlimab showed preliminary clinical responses in pts with advanced/metastatic melanoma and an acceptable safety profile across advanced cancers. Funding: GSK (213348). Clinical trial information: NCT02817633. [Table: see text]