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

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.