Phase Ib Study of BI 836880 (VEGF/Ang2 nanobody) in Combination With Ezabenlimab (anti–PD-1 antibody) in Patients With Advanced or Metastatic Solid Tumors
Year: 2025
Type: article
Study design: Clinical Trial
Abstract: PURPOSE This phase Ib study investigated the safety and antitumor activity of BI 836880, a bispecific nanobody targeting vascular endothelial growth factor and angiopoietin-2, and ezabenlimab, an anti–PD-1 antibody, in patients with advanced or metastatic solid tumors. METHODS This was an open-label, multinational study (ClinicalTrials.gov identifier: NCT03468426 ) conducted in two parts. Part 1 was a dose-escalation phase to determine the recommended phase II dose (RP2D) of BI 836880 in combination with ezabenlimab in patients with metastatic non–small cell lung cancer (mNSCLC). Part 2 was an expansion phase investigating the efficacy and safety of the combination at the RP2D in eight cohorts, on the basis of tumor type. The primary end point of part 2 was objective response rate (ORR). RESULTS Overall, 14 patients were recruited in part 1 and 238 in part 2. In part 1, the maximum tolerated dose of the combination was not reached; the RP2D was BI 836880 720 mg plus ezabenlimab 240 mg every 3 weeks. In part 2, the ORR was 18.9% across all cohorts. In the mNSCLC cohorts, ORRs were 16.7% (after checkpoint inhibitor [CPI] monotherapy) and 7.5% (after chemotherapy + CPI). Notably higher rates were seen in patients with glioblastoma (GBM; 22.6%); hepatocellular carcinoma (HCC) who had previously received sorafenib or lenvatinib (40.0%); and previously untreated HCC (25.8%). The combination was well tolerated; the most common adverse events in part 2 were asthenia (27.3%), hypertension (21.4%), and diarrhea (20.2%). CONCLUSION BI 836880 combined with ezabenlimab had a positive benefit-risk ratio, with a manageable safety profile and signs of antitumor activity across a wide range of tumor types, with particularly promising activity in patients with HCC and GBM.
Source: JCO oncology advances.
DOI: 10.1200/oa-24-00039
Institutions: Institut Curie, Universitat Autònoma de Barcelona, Vall d'Hebron Institute of Oncology, Seoul National University, Seoul National University Hospital, Inserm, Université de Bourgogne, Centre Georges François Leclerc, Seoul National University Bundang Hospital, Centre Hospitalier Universitaire de Nantes, Boehringer Ingelheim (Germany), Boehringer Ingelheim (United States), Boehringer Ingelheim (Spain), The Royal Free Hospital
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: diamond
OpenAlex ID: W4406312638