MO38-1 Phase I Study of BI 836880 Alone or Combined with Ezabenlimab in Japanese Patients (pts) with Advanced Solid Tumors

Inhibition of VEGF/Ang2 and PD-1 can enhance the tumor microenvironment to support T-cell mediated tumor cell destruction. BI 836880 is a humanized bispecific nanobody that targets VEGF and Ang2; ezabenlimab (BI 754091) is an anti-PD-1 antibody. This study determined the maximum tolerated dose (MTD)/recommended phase 2 dose (RP2D) of BI 836880 alone or combined with ezabenlimab in Japanese pts with solid tumors. This open-label, dose-escalation study enrolled pts with advanced solid tumors not amenable to standard therapies. Part 1 assessed BI 836880 monotherapy (starting dose 360 mg iv every 3 weeks [q3w]); Part 2 assessed BI 836880 (starting dose 120 mg iv q3w) + ezabenlimab (240 mg iv q3w). Primary endpoint: MTD of BI 836880 alone and combined with ezabenlimab. Secondary/further endpoints: safety, anti-tumor activity and pharmacokinetics. In Part 1, 9 pts were treated (360 mg: 3, 720 mg: 6). No dose limiting toxicities (DLTs) occurred; MTD was not reached. The most common AEs were hypertension and proteinuria (each 33%). One G3 AE was reported (hypertension). No pts had objective response; 4 had stable disease (SD). In Part 2, 12 pts were treated (120/240 mg: 3, 360/240 mg: 3, 720/240 mg: 6). There were no DLTs during cycle 1; MTD was not reached. Any/G3/G4 AEs occurred in 12/3/1 (100/25/8%) pts. Most common AEs were diarrhea (42%), nausea, hypertension, pyrexia, ALT and AST increased (each 33%). 2 pts had treatment-related serious AEs (G3 abnormal hepatic function [n=1]; G3 abnormal hepatic function, G4 ALT and AST increased [n=1, also leading to treatment discontinuation]). 2 pts had confirmed partial response (both 720/240 mg cohort; small intestine and anal cancer); 5 pts had SD. MTD was not reached in either part; RP2D was BI 836880 720 mg q3w and BI 836880 720 mg + ezabenlimab 240 mg q3w. BI 836880 +/- ezabenlimab had a manageable safety profile and showed preliminary activity in Japanese pts with advanced solid tumors.