{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T20:29:38Z","timestamp":1779913778984,"version":"3.53.1"},"reference-count":31,"publisher":"S. Karger AG","license":[{"start":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T00:00:00Z","timestamp":1774828800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T00:00:00Z","timestamp":1774828800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Liver Cancer"],"abstract":"<jats:p>Introduction: Botensilimab (BOT) is a fragment crystallizable (Fc)-enhanced multifunctional anti-cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) antibody with differentiated mechanisms of action, designed to extend therapy to cold\/poorly immunogenic solid tumors. Patients with hepatocellular carcinoma (HCC) who progress on or after first-line immunotherapy have limited treatment options. Here, we report findings from a phase 1b study of BOT plus balstilimab (BAL; anti-programmed cell death protein 1 [PD-1] antibody) in previously treated patients with HCC. Methods: This is an open-label, nonrandomized, phase 1b, multicenter study of BOT\u00b1BAL in patients with advanced solid tumors. The study began with dose escalation (3 + 3 design) then dose expansion with multiple disease-specific cohorts. An expanded cohort of 19 patients with HCC who progressed on or after prior immunotherapy (primarily atezolizumab\/bevacizumab) are included in this analysis. Patients with HCC received BOT intravenously at 1 or 2 mg\/kg once every 6 weeks for up to 2 years plus BAL intravenously 3 mg\/kg once every 2 weeks, for up to 2 years. Endpoints included safety, objective response rate (ORR), disease control rate, duration of response, and progression-free survival (PFS). Overall survival (OS) was an exploratory endpoint. Results: Among 18 efficacy evaluable patients (with \u22651 post-baseline 6-week imaging scan), ORR was 17% (3\/18; 95% CI: 4\u201341), and 18-week clinical benefit rate (a complete or partial response or stable disease) 50% (9\/18; 95% CI: 26\u201374). Median PFS was 4.4 months (95% CI: 1.4\u20136.9), and median OS was 12.3 months (95% CI: 8.4\u201321.4). Thirteen patients (68%) experienced any-grade immune-mediated treatment-related adverse events (TRAEs), with 37% (7\/19) grade 3. The most common immune-mediated TRAEs included diarrhea\/colitis (37% [7\/19]; 16% grade 3 [3\/19]), hepatitis (21% [4\/19]; 16% grade 3 [3\/19]), and dermatologic events (21% [4\/19]; 5% grade 3 [1\/19]). There were no treatment-related deaths or new safety signals outside of the class. Conclusions: The BOT+BAL combination demonstrated durable responses and manageable safety in treatment-refractory patients with HCC previously treated with immunotherapy, supporting further investigation in randomized studies. Despite the small sample size and high percentage of patients with albumin-bilirubin grade 2 liver disease, these results provide early evidence of antitumor activity in a difficult-to-treat disease setting.<\/jats:p>","DOI":"10.1159\/000551630","type":"journal-article","created":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T16:00:55Z","timestamp":1774886455000},"page":"1-9","source":"Crossref","is-referenced-by-count":1,"title":["A Phase 1b Study of Botensilimab and Balstilimab in Treatment-Refractory Hepatocellular Carcinoma"],"prefix":"10.1159","author":[{"given":"Anthony B.","family":"El-Khoueiry","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher H.","family":"Lieu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1522-8054","authenticated-orcid":false,"given":"Ghassan 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