Phase II study of cobolimab in combination with dostarlimab for the treatment of advanced hepatocellular carcinoma.

580 Background: Immunotherapy is the backbone of hepatocellular cancer (HCC) systemic treatments. Preclinical studies have shown that the combination of anti-TIM-3 antibody and anti-PD-1 antibody is more effective than either therapy alone. Early clinical experience shows that the combination of cobolimab (anti-TIM-3) and dostarlimab (anti-PD-1) can be safely administered. Herein we report an interim update to this phase II, single arm study of cobolimab and dostarlimab in patients with untreated advanced HCC. We hypothesize that this combination immune checkpoint inhibitor therapy will increase the overall response rate (ORR) of patients from 20% (historical control) to 35%. Methods: In total, 42 patients with histologically confirmed, Barcelona Clinic Liver cancer (BCLC) stage B or C HCC will be enrolled on to this trial. Patients receive cobolimab 300 mg and dostarlimab 500 mg on day 1 of each 21-day cycle for up to two years or until disease progression, unacceptable toxicity, or patient withdrawal. CT or MRI is performed every 9 weeks to assess clinical response. The primary objective is to assess ORR. Results: At the cutoff date of September 1, 2022, 16 patients had been enrolled and received at least one dose of cobolimab and dostarlimab. The median age was 68 years (range 44 – 84); most were male (n=15); 5 were White, 5 Native Hawaiian, 4 Asian, and 2 other races. 3 patients had stage BCLC B and 13 had stage BCLC C disease; 1 had Hep B and 5 had Hep C; and 14 were Child Pugh A and 2 Child Pugh B. This interim analysis for efficacy includes 13 patients who had at least one post-baseline tumor assessment (or clinical progression or died). Complete response was seen in 1 patient, partial response in 5 patients (ORR 46%), stable disease in 3 patients (23%), and disease progression in 4 patients (31%). Of the 7 patients with an elevated AFP at baseline, 4 (57%) had a decrease in AFP level by greater than 50%. There was one grade 4 treatment-related adverse event (AE) of neutropenia. Grade 1/2 AEs included pruritus, rash, fatigue, hypothyroidism, and elevated AST and ALT. Conclusions: Interim results indicate that the combination of cobolimab and dostarlimab has acceptable safety with encouraging clinical activity as first line treatment in patient with advanced HCC. To our knowledge, this is the first report of clinically meaningful efficacy of a TIM-3 antibody in combination with a PD-1 antibody in patients with HCC. Clinical trial information: NCT03680508 .