Cobolimab and dostarlimab in the first-line treatment of unresectable hepatoma: A multi-center, single arm, phase 2 trial.

4099 Background: TIM-3 is highly expressed in cancer and mediates T cell exhaustion/dysfunction that can be an important mechanism of immune escape. Cobolimab, an anti-TIM-3 monoclonal antibody, in combination with dostarlimab (a PD-1 inhibitor), has been shown to enhance T-cell activity in preclinical assessments. This study aimed to investigate the efficacy and safety of cobolimab and dostarlimab in the treatment of unresectable hepatocellular carcinoma (HCC). Methods: This is a multi-center, single-arm, phase II study. Eligible patients with unresectable hepatoma (Barcelona Clinic Liver Cancer Stage B or C) and Child Pugh A or B7 (limit 6) liver function received cobolimab 300mg and dostalimab 500mg every 3 weeks for up to 2 years. The primary endpoint was the objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors version1.1. Secondary endpoints were disease control rate (DCR) and duration of response (DoR), progression-free survival (PFS), overall survival (OS), and safety. Results: 40 patients were treated (mean age 67 years [range: 24–85]). The analysis presented here is for all 34 Child Pugh A patients. As of November 6, 2024, the median follow-up was 12.9 months. The ORR and DCR were 37.1% and 85.2% respectively (3.7% CR, 33.3% PR, 48.1% SD). The median PFS was 11.0 mo (95% CI: 4.6-17.4), and the median OS was 27.3 mo (95% CI: 21.1-33.5). The median DoR was 14.8 mo (95% CI: 9.4-20.2). Overall incidences of adverse events (AEs) of any grade was 97.1% and immune-related AEs (irAEs) of any grade was 64.7%. The most common irAEs of any grade were dermatologic (47.1%) and endocrine (14.7%). There were two patients (5.8%) who experienced mild elevations of AST and ALT. Grade ≥3 irAEs were observed in two patients (5.8%), which included decreased neutrophil count, hypophysitis, and hypothyroidism. There were no treatment-related discontinuations or deaths. Conclusions: Cobolimab plus dostarlimab yielded promising response rates and survival outcomes with acceptable safety as first-line treatment in patients with CP A, unresectable HCC. This represents a potential therapy regimen for this population. Clinical trial information: NCT03680508 .