Abstract LB365: Results from a phase 1 study of botensilimab and balstilimab in treatment refractory hepatocellular carcinoma

Abstract Effective therapy options for patients (pts) with hepatocellular carcinoma (HCC) who progress on or after first-line immunotherapy (I-O) are limited. Botensilimab (BOT) is an Fc-enhanced, multifunctional CTLA-4 inhibitor with differentiated mechanisms of action designed to extend therapy to cold or poorly immunogenic solid tumors. BOT alone or when combined with balstilimab (BAL; PD-1 inhibitor comparable to other PD-1 inhibitors) has demonstrated durable responses across 9 different treatment-refractory solid tumors, including those resistant to prior I-O. Here, we evaluated the safety and efficacy of BOT±BAL in a phase 1 trial of advanced solid tumors with a dedicated expansion cohort of pts with HCC treated with BOT/BAL who progressed on or after prior I-O (NCT03860272).As of Dec 5, 2024, 19 pts (safety population) with HCC who progressed on or after prior I-O (median follow-up 11.4 mos [range 1.5–34.3]) were treated with BOT (1 or 2 mg/kg every 6 wks) plus BAL (3 mg/kg every 2 wks). Pts were considered efficacy evaluable if they received ≥1 post baseline imaging scan (n=18). In the safety population, median age was 67 yrs (range 39–82), 79% were male, 68% had extrahepatic metastases, 53% had an ALBI score of 1, 47% ALBI 2, 42% were HepB positive, and 21% HepC positive. Pts received a median of 2 prior lines of therapy (range 1–7); all had received prior PD-(L)1 as part of combination therapy (58% atezolizumab/bevacizumab [atezo/bev]) and 63% received prior receptor tyrosine kinase inhibitors. The objective response rate by RECIST 1.1 was 17% (3 partial responses [PRs]/18; 95% CI 3%–40%) and median duration of response was not reached (range 2.8+ to 25.0+ mos). The clinical benefit rate (complete response, PR or stable disease ≥18 wks) was 47% (95% CI 24%–71%). Notably, 5 pts had SD ≥24 wks, including 1 pt with SD=66 wks. Median OS was 12.3 mos (95% CI 8.4–21.4). All 3 responders received prior atezo/bev; 1 also received lenvatinib; another also received sorafenib and a MER/AXL-targeted therapy (clinical trial). As of the data cutoff, all 19 pts had discontinued treatment and 5 remained in survival follow-up. Immune-mediated treatment-related adverse events (imAEs) of any grade occurred in 68% of pts (37% G3) in the safety population. The most common imAE was diarrhea/colitis occurring in 37% of pts (16% G3), followed by hepatitis (21%; 16% G3) and skin adverse reactions (21%; 5% G3). 12 pts (63%) received systemic steroids or TNF-α inhibitors for an imAE, while 3 (16%) received thyroid hormone replacement. There were no treatment-related deaths. The BOT/BAL combination demonstrated durable responses and prolonged SD in pts with treatment refractory HCC (median of 2 prior therapies and progressed on or after I-O), including those who had received prior atezo/bev. The safety profile was manageable and consistent with other disease cohorts treated with BOT/BAL. These results support further investigation. Citation Format: Anthony B. El-Khoueiry MD, Ghassan K. Abou-Alfa MD, PhD, JD, MBA, Breelyn A. Wilky MD, Apostolia M. Tsimberidou MD, PhD, Daruka Mahadevan MD, PhD, Diana L. Hanna MD, Bruno Bockorny MD, Daniel E. Fein MD, Christopher H. Lieu MD, Alexis Leal MD, Cara Constance PhD, BSN, Manushak Avagyan MD, MPH, Wei Wu MS, Joseph E. Grossman MD, Benny Johnson DO, Andrea J. Bullock MD. Results from a phase 1 study of botensilimab and balstilimab in treatment refractory hepatocellular carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_2):Abstract nr LB365.