Abstract CT253: Preliminary safety and efficacy data of BGB-A333, an anti-PD-L1 monoclonal antibody, alone and in combination with tislelizumab in patients with advanced solid tumors
Authors: Desai Jayesh , Voskoboynik Mark , Markman Ben , Frentzas Sophia , Foster Paul , Budha Nageshwar , Song Jing , Meniawy Tarek 
Published: September 2020

Abstract
Background: Programmed cell death protein-1 (PD-1) and its ligand, programmed death-ligand 1 (PD-L1), play critical roles in the immune modulation of tumor progression. Although both pathways have overlapping elements, each has a distinct mechanism of action. Nonclinical studies have demonstrated that potential synergistic antitumor effects can result from blocking both PD-1 and PD-L1. BGB-A333 is an investigational humanized IgG1 monoclonal antibody against PD-L1 that has antitumor activity in xenograft models. Tislelizumab, a clinical-stage anti-PD-1 antibody engineered to minimize binding to FcγR on macrophages in order to abrogate antibody-dependent phagocytosis, has demonstrated clinical activity in patients with advanced solid tumors. Here we report preliminary results from the phase 1 component of an open-label phase 1/2 study (NCT03379259) of BGB-A333 alone and in combination with tislelizumab in patients with advanced solid tumors.
Methods: Phase 1 of this study consisted of two parts. In Part A, patients received single-agent BGB-A333 IV Q3W at increasing doses; in Part B patients received BGB-A333 1350 mg IV Q3W + tislelizumab 200 mg IV Q3W. Eligible patients had unresectable advanced or metastatic cancer and an ECOG performance status of ≤1. Safety/tolerability profile (primary endpoint) was examined by monitoring adverse events (AEs); secondary endpoints included antitumor activity, assessed by RECIST v1.1, and the pharmacokinetic (PK) parameters of each antibody. Results: As of Oct 30, 2019, 15 patients were enrolled in Part A (450 mg, n=3; 900 mg, n=3; 1350 mg, n=6; 1800 mg, n=3) and 12 in Part B. Across both parts, patients were female (n=17/29; 63%); squamous cell carcinoma of either skin or head and neck (n=5) and ovarian cancer (n=4) were the most common tumor types. Thirteen patients (48%) had ≥2 lines of prior systemic therapy. The most common treatment-related AEs (TRAEs) were fatigue (N=5; Part A, n=3; Part B, n=2) and nausea (N=4; n=2 in A and B); the only grade ≥3 TRAE occurring in ≥1 patient was grade 3 maculo-papular rash (N=2; n=1 in A and B). One patient in Part B experienced a fatal AE (acute kidney injury) considered possibly related to study treatment. Of the 15 patients receiving BGB-A333 monotherapy in Part A, three (20%) achieved a confirmed complete response and two (13.3%) achieved a partial response (PR). Two of the 12 (16.7%) patients receiving combination therapy in Part B achieved a PR. The PK of BGB-A333 was comparable to a typical IgG1 antibody, and was similar as a single-agent or in combination with tislelizumab. The PK of tislelizumab was comparable with historical data. Conclusions: BGB-A333, alone or in combination with tislelizumab, was generally well tolerated and demonstrated antitumor activity in patients with advanced solid tumors. Based on these data, expansion cohorts have been initiated.
Citation Format: Jayesh Desai, Mark Voskoboynik, Ben Markman, Sophia Frentzas, Paul Foster, Nageshwar Budha, Jing Song, Tarek Meniawy. Preliminary safety and efficacy data of BGB-A333, an anti-PD-L1 monoclonal antibody, alone and in combination with tislelizumab in patients with advanced solid tumors [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr CT253.