BI-1808 + pembrolizumab: Responses to a chemotherapy-free regimen in advanced ovarian cancer.

Abstract

2605 Background: Up to 80% of individuals with advanced ovarian cancer experience disease progression after standard platinum-based chemotherapy, leaving few approved therapeutic options and poor prognosis. Anti-PD-1 therapies such as pembrolizumab have shown modest efficacy in recurrent ovarian cancer as single agent therapy with an ORR of 8% (KEYNOTE-100), while adding pembrolizumab to weekly paclitaxel±bevacizumab regimen (KEYNOTE-B96) demonstrates statistically meaningful improvement in OS and PFS in all comers and the PD-L1 CPS ≥1 population. BI-1808 is an IgG1 mAb targeting TNFR2. It blocks TNF-α binding and, via FcγR engagement, depletes Tregs and reprograms myeloid cells, expanding antitumor CD8+ T cells. These mechanisms of action differentiate BI-1808 from the relief of T cell suppression mediated by anti-PD1. Accordingly, in preclinical models BI-1808 synergizes with anti-PD-1 leading to an additive tumor inhibition. During BI-1808 monotherapy exploration, one case of complete response in a platinum-resistant patient was observed. The combination of BI-1808 and pembrolizumab could offer a chemotherapy-free treatment alternative in ovarian cancer. Methods: Safety and efficacy of BI-1808 plus pembrolizumab are being evaluated in patients with advanced pretreated ovarian cancer in a sub-cohort of the ongoing Phase 2a trial (19-BI-1808-01). The signal-seeking cohort aimed to enroll 20 patients at BI-1808 1000 mg Q3W plus pembrolizumab 200 mg Q3W, followed by dose optimization. Results: As of Dec 18, 2025, 24 subjects received BI-1808 plus pembrolizumab. Among 17 response-evaluable patients, 4 achieved confirmed partial response (ORR 24%). Disease control rate was 65%, with 7 patients showing prolonged stable disease, several ongoing beyond 10 months. Strong activity was observed in both high-grade serous and clear cell subtypes. The combination was generally safe and well tolerated; immune related events were manageable and did not lead to treatment discontinuation. Analysis of circulating immune cells shows significant T reg depletion and strong signs of CD8 + T cell activation. Conclusions: Early data from this cohort are highly encouraging, with ORR 24% and DCR 65%. BI-1808 plus pembrolizumab demonstrated a manageable safety profile and promising activity in advanced heavily pretreated ovarian cancer. Based on these findings, the cohort will expand by 20 additional patients focusing on clear cell and high-grade serous subtypes. Further data, including biomarker analyses, will be presented on poster. Clinical trial information: NCT04752826 .