{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T07:59:11Z","timestamp":1782287951749,"version":"3.54.5"},"reference-count":41,"publisher":"BMJ","issue":"12","license":[{"start":{"date-parts":[[2025,12,23]],"date-time":"2025-12-23T00:00:00Z","timestamp":1766448000000},"content-version":"unspecified","delay-in-days":22,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Agenus Inc","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Immunother Cancer"],"accepted":{"date-parts":[[2025,11,23]]},"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Patients with platinum-resistant\/refractory ovarian cancer (PROC) experience suboptimal outcomes, highlighting an immediate need for novel therapies. This phase 1b study investigated the safety and efficacy of botensilimab (BOT), a fragment crystallizable (Fc)-enhanced anti\u2013cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) antibody with differentiated mechanisms of action from first-generation CTLA-4 inhibitors, plus balstilimab (BAL; anti\u2013programmed cell death protein 1 antibody), in an expanded cohort of patients with treatment-refractory ovarian cancer.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>BOT was administered intravenously at 1\u2009mg\/kg or 2\u2009mg\/kg every 6 weeks in combination with BAL intravenously at 3\u2009mg\/kg every 2 weeks (up to 2 years). The primary objectives were to assess safety and tolerability. Efficacy end points included objective response rate (ORR), duration of response (DOR), and progression-free survival (PFS) by Response Evaluation Criteria in Solid Tumors (RECIST) V.1.1. Overall survival (OS) was an exploratory end point.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Overall, 44 patients were evaluable for safety (with a median of 3 prior lines of therapy; median follow-up 9.6 months (range, 0.6\u201436.6)), and 35 for efficacy. The most common treatment-related adverse event was diarrhea\/colitis (43%; 16% grade 3) with no treatment-related deaths. RECIST-confirmed ORR was 23% (8\/35; 95%\u2009CI 10% to 40%; one complete (CR), seven partial responses (PRs)) and clinical benefit rate (CR, PR, or stable disease \u226524 weeks) was 31% (11\/35; 95%\u2009CI 17% to 49%). Median DOR was 9.7 months (95%\u2009CI 2.8 to not reached (NR)), median PFS was 2.8 months (95%\u2009CI 1.4 to 5.5), median OS was 14.8 months (95%\u2009CI 12.1 to NR), and 12-month OS was 75% (95% CI 55% to 86%). Immune phenotypic analyses and biomarker data revealed significantly higher Fc\u03b3RIIIA+CD11c+ cells and higher programmed death-ligand 1 expression in responding patients, a strong association between T-cell infiltrated tumors and clinical benefit, and differences in immune architecture across histologic subtypes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The BOT\/BAL combination demonstrated deep, durable responses and complete remissions in patients with treatment-refractory ovarian cancer where no standard treatments are currently available. RECIST under-represented clinical benefit with 11 patients achieving prolonged\/clinically meaningful stable disease (or better) for \u226524 weeks. Toxicities were manageable and reversible. The encouraging clinical activity of BOT\/BAL in heavily pretreated patients, as well as biomarker associations, warrants further investigation of this combination.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/jitc-2025-013222","type":"journal-article","created":{"date-parts":[[2025,12,23]],"date-time":"2025-12-23T14:25:12Z","timestamp":1766499912000},"page":"e013222","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":5,"title":["Botensilimab (Fc-enhanced anti\u2013CTLA-4 antibody) plus balstilimab (anti\u2013PD-1 antibody) in patients with treatment-refractory ovarian 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