An open-label, phase I trial of BI 754091 alone and in combination with BI 754111 in Asian patients (pts) with advanced solid tumors.

Abstract

3054 Background: Dual blockade of immune checkpoint molecules, PD-1 and LAG-3, may enhance the anti-tumor response versus PD-1 blockade alone. This Phase I trial investigated BI 754091, an anti-PD-1 antibody, as monotherapy and in combination with BI 754111, an anti-LAG-3 antibody, in Asian pts with advanced solid tumors. Methods: This trial comprised 3 parts. Parts 1 and 2 (dose escalation) were in pts with unresectable/metastatic solid tumors. In Part 1, pts received BI 754091 240 mg intravenously (iv), every 3 weeks (q3w); in Part 2, pts received BI 754091 240 mg in combination with BI 754111 (400 mg, 600 mg or 800 mg iv, q3w). Dose escalation was guided by a Bayesian logistic regression model, with overdose control. The primary endpoint in Parts 1 and 2 was maximum tolerated dose (MTD) of BI 754091 alone or in combination with BI 754111, based on dose-limiting toxicities (DLTs) in Cycle 1. In Part 3, BI 754091 240 mg plus BI 754111 600 mg q3w was assessed in 4 expansion cohorts. Cohorts A–C included pts with: A) gastric/esophagogastric junction cancer; B) esophageal cancer; C) hepatocellular cancer; all had received ≥1 line of prior systemic therapy and no prior anti-PD-(L)1 therapy. Cohort D included pts who had received prior anti-PD-(L)1 therapy for the tumor types in Cohorts A–C. The primary endpoint in Part 3 was objective response (confirmed complete response or partial response [PR] per RECIST 1.1). Results: In Part 1, 6 pts received BI 754091 240 mg. In Part 2, 9 pts received BI 754091 240 mg plus BI 754111 (400 mg/600 mg/800 mg; n = 3 per cohort). No DLTs were reported in Parts 1 and 2. In Part 3, 121 pts were treated (97 [80%] male, median age 61 years [range 23–80]); Cohorts A/B/C/D included 33/33/20/35 pts. All-grade adverse events (AEs) and treatment-related AEs (TRAEs) were experienced by 96 (79%) and 47 (39%) pts, respectively. The most commonly reported AEs (all/≥G3) were pyrexia (21%/0%), decreased appetite (17%/2%), anemia (11%/6%), and nausea (9%/0%). 36 (30%) pts reported immune-related AEs, most commonly hypothyroidism, in 7 (6%) pts. Confirmed PR was observed in 6 pts (5%; Cohort A/B, n = 4/2) and 35 (29%) pts had stable disease (Cohort A/B/C/D, n = 9/11/10/5). Conclusions: MTD was not reached for BI 754091 monotherapy or for BI 754091 in combination with BI 754111. The recommended dose for the combination was determined as BI 754091 240 mg plus BI 754111 600 mg q3w. Treatment was well tolerated and consistent with that observed in the global trial. Preliminary anti-tumor activity was seen. Clinical trial information: NCT03433898 .