Preliminary Phase 1 Results of the PD-1 Inhibitor ABBV-181 in Japanese vs Western Patients With Advanced Solid Tumors

Abstract

Abstract Background ABBV-181 is a monoclonal antibody that binds to cell surface programmed cell death 1 (PD-1). Dose-finding data have been previously reported (Powderly et al, Ann Oncol 2018). This report summarizes ABBV-181 monotherapy data from Japanese (JPN) and cohort-matched Western (WST) patients (pts) enrolled in the first-in-human study evaluating ABBV-181 in pts with previously treated advanced solid tumors (NCT03000257). Methods Pts received ABBV-181 in a 3 + 3 dose-escalation design at 1, 3, and 10 mg/kg IV every 2 weeks (Q2W) until progression (JPN pts: 3 and 10 mg/kg only) and a basket expansion cohort at a recommended phase 2 dose (RP2D). Response was assessed Q8W per Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 and immune RECIST. Serial pharmacokinetic (PK) and pharmacodynamic samples were collected. Results As of Nov 2018, 56 pts (JPN: 11) were enrolled (total and JPN pts, median days on treatment [range], 1 mg/kg: 12, 120 [43-653]; 3 mg/kg: 10 and 4, 64 [1-134] and 29 [15-106]; 10 mg/kg: 11 and 4, 64 [1-225] and 29 [1-85]; basket: 23 and 3, 29 [1-353] and 15 [15-16]). Adverse events (AEs) were reported in (total, JPN pts): 10, 4 (3 mg/kg); 10, 3 (10 mg/kg); and 22, 2 (basket), with 5, 1 (3 mg/kg); 4, 0 (10 mg/kg); and 15, 1 (basket) pts having Grade (G)≥3 AEs. No dose-limiting toxicities or drug-related G5 AEs were reported. The most common G ≥ 1 AEs in JPN pts were (%): pyrexia (36), anemia (27), constipation (18); G ≥ 3 AEs were: anemia, decreased appetite, progression (9% each, all unrelated to ABBV-181). One G5 AE of progression was reported. Seven of 11 JPN pts discontinued ABBV-181 (all for disease progression). ABBV-181 PK appears dose-proportional and comparable in JPN and WST pts. ABBV-181 led to complete PD-1 receptor occupancy, similar kinetics of cytokine induction, and transient T-cell changes in JPN and WST pts. Conclusion These results support a RP2D of 250 mg Q2W, 375 mg Q3W, or 500 mg Q4W in both JPN and WST pts.