NOVEL combination therapy shows promising clinical antitumor activity in patients with heavily pretreated recurrent ovarian cancer.
Interim clinical results from an ongoing Phase 1/2a clinical trial, registered as NCT04752826, demonstrate significant therapeutic progress for advanced solid tumors. The trial evaluated a novel investigational combination comprising BI-1808 and pembrolizumab administered without concurrent chemotherapy. The evaluation focused on patients diagnosed with recurrent ovarian cancer who experienced disease progression following multiple prior lines of platinum-based therapy. Patients with platinum-resistant recurrent ovarian cancer represent a population with substantial unmet clinical needs, where historical single-agent programmed cell death protein 1 inhibitor therapy yields an overall response rate of approximately 8%.
In contrast, the combination regimen achieved a confirmed objective response rate of 24%, including a complete response, representing a threefold increase over historical monotherapy benchmarks. The disease control rate reached 56%, with multiple patients experiencing durable clinical responses extending beyond 10 months while remaining on active treatment. Preliminary survival analyses demonstrated a median progression-free survival of 10.3 months. Antitumor activity was observed across both high-grade serous and clear cell histological subtypes. Furthermore, this chemotherapy-free regimen exhibited favorable tolerability, leading to low rates of treatment discontinuation due to adverse events.
The Phase 1/2a trial evaluated preliminary efficacy using standardized RECIST v1.1 and iRECIST criteria alongside pharmacodynamic biomarkers. Investigators established that BI-1808 acts as a first-in-class monoclonal antibody targeting tumor necrosis factor receptor 2, a receptor selectively upregulated on regulatory T cells within the tumor microenvironment. By depleting immunosuppressive regulatory T cells, reprogramming tumor-associated myeloid cells, and promoting CD8-positive T-cell infiltration, the treatment successfully transforms immunologically cold tumors into inflamed, responsive microenvironments.
Primary endpoints for the multi-part study include safety, characterization of pharmacokinetics, overall response rate, duration of response, and progression-free survival. The study design encompasses single-agent evaluation, combination therapy with anti-PD-1 agents, and combination therapy with standard chemotherapy across solid tumors and cutaneous T-cell lymphoma. Target cohort expansions remain ongoing to establish long-term clinical utility in recurrent ovarian cancer.
Reference
National Library of Medicine. BI-1808 as a Single Agent and With Pembrolizumab (KEYTRUDA®) in Treatment of Advanced Malignancies (Keynote-D20). ClinicalTrials.gov. 2026; NCT04752826.
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