A Phase 1/2 study of the PD-L1 inhibitor, BGB-A333, alone and in combination with the PD-1 inhibitor, tislelizumab, in patients with advanced solid tumours
Jayesh Desai, Peter C.C. Fong, Víctor Moreno, Sophia Frentzas, Tarek Meniawy, Ben Markman, Mark Voskoboynik, Tahmina Rahman, Nageshwar Budha, John Wu, Jin Marlow, Silu Yang, Emiliano Calvo, Juan Martín-Liberal
Abstract
BACKGROUND: Many patients do not respond or eventually relapse on treatment with programmed cell death protein-1 (PD-1)/programmed death-ligand 1 (PD-L1) checkpoint inhibitors due to secondary or acquired resistance; therefore, there is a need to investigate novel PD-1/PD-L1 inhibitors. METHODS: This open-label, non-randomised study investigated the safety and anti-tumour activity of BGB-A333, a PD-L1 inhibitor, alone and in combination with tislelizumab in patients with advanced solid tumours with progression during/after standard therapy. The primary objectives were to determine the recommended Phase 2 dose (RP2D), safety and tolerability for BGB-A333 alone and in combination with tislelizumab (Phase 1a/1b) and to determine the overall response rate (ORR) with BGB-A333 plus tislelizumab (Phase 2). RESULTS: Overall, 39 patients across Phase 1a (N = 15), 1b (N = 12) and 2 (N = 12) were enroled. In Phase 1a, an RP2D of 1350 mg was determined. In Phase 1a and 1b/2, serious treatment-emergent adverse events (TEAEs) were reported in five and eight patients, respectively. Two patients experienced TEAEs that led to death. In Phase 2, the ORR was 41.7% (n = 5/12; 95% confidence interval: 15.17%, 72.33%). CONCLUSIONS: TEAEs reported with BGB-A333 were consistent with other PD-L1 inhibitors. Encouraging preliminary anti-tumour activity was observed with BGB-A333 in combination with tislelizumab. CLINICAL TRIAL REGISTRATION: NCT03379259.