AMBER part 2F: Cobolimab in combination with dostarlimab in treatment-naïve patients with locally advanced/metastatic and/or unresectable hepatocellular carcinoma (HCC).

Abstract

TPS650 Background: The introduction of targeted treatment (tx) and immune checkpoint inhibitors (ICIs) has transformed the 1L advanced/metastatic (A/M) HCC tx landscape. 1 Combinations of ICIs with anti-angiogenic agents or other ICIs have demonstrated synergism in patients (pts) with A/M HCC, and shown improved efficacy versus single agents or tyrosine kinase inhibitors. 1,2 Combinations with anti-T-cell immunoglobulin and mucin-domain containing-3 (TIM-3) and anti-programmed cell death protein-1 (PD-1) ICIs have shown promising anti-tumor activity in pts with solid tumors 3,4 including advanced HCC in US pts. 5 AMBER (NCT02817633) part 2F will evaluate the efficacy and safety of anti-TIM-3 cobolimab plus anti-PD-1 dostarlimab in tx-naïve pts with A/M and/or unresectable HCC. Methods: AMBER is a two-part, global, open-label, Phase Ib study assessing cobolimab as monotherapy or in combination with other drugs in pts with advanced solid tumors. For part 2F, ~45 pts are planned for enrollment. Key eligibility includes pts aged ≥18 years, with Eastern Cooperative Oncology Group (ECOG) performance score 0–1, histologically confirmed A/M HCC with measurable disease, Child-Pugh Class A liver function, no prior systemic tx, documented hepatitis B and C test at screening, and a pre-tx biopsy sample. Eligible pts will receive cobolimab (300 mg IV) plus dostarlimab (500 mg IV) every 3 weeks (Q3W) for up to 2 years or until progression, toxicity, discontinuation, or death. The primary endpoint is investigator-assessed objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1); secondary endpoints include investigator-assessed disease control rate (DCR), duration of response (DOR) and progression-free survival (PFS) per RECIST v1.1, and overall survival, alpha-fetoprotein response, and safety. Exploratory endpoints include immune-related (ir)-ORR, irDCR, irDOR and irPFS per irRECIST, and biomarker and pharmacokinetic assessments. Disease assessments will consist of CT/MRI evaluations of the chest, abdomen, and pelvis, Q9W from first dose then Q12W after 1 year of tx. Pts will undergo safety follow-up at 30 and 90 (±7) days after last study tx. Efficacy analysis will be based on the safety population (pts who receive ≥1 cobolimab dose) and will include summary statistics and point estimates with 2-sided 95% confidence intervals. Time-to-event analyses will be performed via Kaplan–Meier methods. After ~25 pts have been followed-up for ≥3 scans, an interim analysis may be performed. References: 1. Gordan JD, et al. J Clin Oncol . 2024:42:1830–50; 2. Finn RS, et al. N Engl J Med . 2020;382:1894–1905; 3. Curigliano G, et al. Clin Cancer Res. 2021;27:3620–29; 4. Davar D, et al. J ImmunoTher Cancer . 2023:11(Suppl 1):596; 5. Acoba JD, et al. J Clin Oncol . 2023:41:580. Funding: GSK (213348). Clinical trial information: NCT02817633 .