Phase I study of spartalizumab (PDR001), an anti-PD1 mAb, in Japanese patients with advanced malignancies

Background: Spartalizumab, a humanized IgG4 anti-PD1 mAb, blocks interaction with the ligand PD-L1. Previously published clinical data show a favorable safety profile and antitumor activity in non-Japanese patients (pts). Methods: This Phase I, open-label, dose-escalation study (NCT02678260) characterized the safety, PK, and efficacy of spartalizumab in Japanese pts with advanced malignancies who progressed on standard therapy. The primary objective was to determine the recommended dose (RD)/maximum tolerated dose (MTD). Results: 18 pts received spartalizumab Q2W in 3 dose groups: 1, 3, and 10 mg/kg (n = 6 each). Median age was 53 yrs (range 29-75), 39% of pts were male, 83% had received ≥3 prior medications (all were pretreated). Most common cancer types were ovarian (17%), head and neck, cervical, and triple negative breast cancer (11% each). No DLTs were reported at any tested dose; MTD was not reached. Treatment-related AEs were reported for 11 pts (61%); most commonly (>10%) maculopapular rash (22%), malaise, alkaline phosphatase increased (each 11%). Treatment-related G3/G4 AEs (1 pt each, 6%) were creatine phosphokinase increased and alkaline phosphatase increased. ORR (per RECIST 1.1) was 11% (2/18); partial responses were seen in pts with HCC and transitional cell carcinoma. Stable disease was the best overall response in 22% of pts (4/18); disease control rate was 33%. PK exposure increased dose-proportionally, half-life was 12-22 days, and AUC accumulation was approximately 2-fold. PK data did not suggest ethnic difference. Conclusion: Spartalizumab was well tolerated in Japanese pts. As safety and PK profiles were comparable with previous trials in non-Japanese pts, RDs selected for non-Japanese pts (400 mg Q4W; 300 mg Q3W) were considered suitable for Japanese pts (pending further investigation). Preliminary efficacy was observed in a heavily pretreated and heterogenous population. Data support further clinical development of spartalizumab for Japanese pts.