535MO - BGB-A333, an anti-PD-L1 monoclonal antibody, in combination with tislelizumab in patients with urothelial carcinoma

Background

Preclinical studies have shown potential synergism from blocking both programmed cell death protein-1 (PD-1) and programmed death-ligand 1 (PD-L1). BGB-A333 is an investigational humanized monoclonal antibody against PD-L1 that has antitumor activity in xenograft models. Tislelizumab, a clinical-stage anti-PD-1 antibody, showed clinical activity in patients (pts) with advanced solid tumors. We report results from the expansion cohort (phase IIB) of an open-label phase I/II study (NCT03379259) of BGB-A333 plus tislelizumab in pts with previously treated advanced urothelial carcinoma (UC).

Methods

Patients received BGB-A333 1350 mg IV Q3W + tislelizumab 200 mg IV Q3W. Eligible pts had locally advanced or metastatic UC without prior PD-(L)1 therapy, could not tolerate or progressed during/after treatment with platinum-based chemotherapy, and had an ECOG performance status of ≤1. The primary endpoint was investigator-assessed objective response rate (ORR) per RECIST v1.1. Key secondary endpoints included duration of response (DoR) per RECIST v1.1, progression-free survival (PFS) estimated with Kaplan-Meier analysis, and the safety/tolerability profile evaluated by monitoring adverse events (AEs).

Results

As of 10 March 2020, 12 pts (median age, 69.5 yr; 92% male) with UC were enrolled; median study follow-up, 8.3 mo. Most pts (n=10, 83%) had 1 prior systemic therapy. Median duration of treatment for both BGB-A333 and tislelizumab was 5.5 mo (range: 1.2, 9.9). Confirmed ORR was 42% (95% CI: 15.2, 72.3); 3 pts had complete responses, 2 had partial responses, 4 had stable disease (SD; 2 had SD >6 mo), 2 had progressive disease, and 1 was not evaluable (due to missing postbaseline assessment). Median DoR was not reached; median PFS was 6.1 mo (95% CI: 1.9, not estimable). Across the entire study (n=39), treatment-related AEs (TRAEs) occurred in 19 pts. Of the 24 pts receiving combination treatment, four pts (including one with UC) had grade ≥3 TRAEs. One pt with UC had an immune-related AE (myositis); no pts with UC had a fatal TRAE.

Conclusions

BGB-A333 in combination with tislelizumab was well tolerated and demonstrated antitumor activity in pts with advanced UC.

Clinical trial identification

NCT03379259.

Editorial acknowledgement

Writing and editorial assistance was provided by Stephan Lindsey, PhD, and Elizabeth Hermans, PhD (OPEN Health Medical Communications, Chicago. IL), and funded by the study sponsor.

Legal entity responsible for the study

BeiGene, Ltd.

Funding

BeiGene, Ltd.

Disclosure

J. Martin Liberal: Speaker Bureau/Expert testimony, lecture fees: Astellas; Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses, Lecture fees, advisory fees, travel grant: BMS; Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses, Lecture fees, advisory fees, travel grant: Merck Sharp & Dohme (MSD); Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses, Lecture fees, advisory fees, travel grant: Novartis; Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses, Lecture fees, advisory fees, travel grant: Pierre Fabre; Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses, Lecture fees, travel grant: Pfizer; Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses, Lecture fees, advisory fees, travel grant: Roche; Travel/Accommodation/Expenses, travel grant: Ipsen. P.C. Fong: Honoraria (self): AstraZeneca, Merck Sharp & Dohme; Advisory/Consultancy: Merck Sharp & Dohme; Speaker Bureau/Expert testimony: Janssen; Travel/Accommodation/Expenses: Pfizer. V. Moreno: Travel/Accommodation/Expenses, Personal Fees: BMS; Travel/Accommodation/Expenses, Personal Fees: Bayer; Travel/Accommodation/Expenses, Personal Fees: Pieris. J. Desai: Advisory/Consultancy: Amgen; Advisory/Consultancy: BeiGene; Advisory/Consultancy, Research grant/Funding (institution): Bionomics; Advisory/Consultancy: Eisai; Advisory/Consultancy: Lilly; Advisory/Consultancy, Research grant/Funding (institution): Novartis; Research grant/Funding (institution): Roche; Research grant/Funding (institution): GlaxoSmitKline. B. Markman: Advisory/Consultancy: Novartis; Advisory/Consultancy: Amgen. M. Voskoboynik: Travel/Accommodation/Expenses, personal fees: MSD; Travel/Accommodation/Expenses, personal fees: AstraZenca. N. Budha: Shareholder/Stockholder/Stock options, Full/Part-time employment: BeiGene, Ltd. J. Wu: Shareholder/Stockholder/Stock options, Full/Part-time employment: BeiGene, Ltd. W. Shen: Full/Part-time employment: BeiGene, Ltd. M. Singh: Full/Part-time employment: BeiGene, Ltd. E. Calvo: Advisory/Consultancy, Research grant/Funding (institution): Boehringer-Ingelheim; Research grant/Funding (institution): Roche/Genentech; Research grant/Funding (institution): BMS; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Novartis; Advisory/Consultancy, Research grant/Funding (institution): PsiOxus; Advisory/Consultancy, Research grant/Funding (institution): Nanobiotix Janssen; Advisory/Consultancy, Research grant/Funding (institution): AbbVie; Research grant/Funding (institution): PharmaMar; Research grant/Funding (institution): Puma, Sanofi, Lilly, Pfizer, Merck, Nektar; Advisory/Consultancy: Nanobiotix, AbbVie, AstraZenca, Guidepoint Global, GLG, PFizer, Servier, Amcure; Advisory/Consultancy, Travel/Accommodation/Expenses: Roche/Genentech,; Honoraria (self), Full/Part-time employment: Hm Hospitals Group; Research grant/Funding (institution): Merck; Research grant/Funding (institution): Nektar; Research grant/Funding (institution): Amcure; Research grant/Funding (institution): Amgen; Research grant/Funding (institution): AstraZeneca; Research grant/Funding (institution): Principia Bayer; Research grant/Funding (institution): CytomX; Research grant/Funding (institution): H3; Research grant/Funding (institution): Incyte; Research grant/Funding (institution): Kura; Research grant/Funding (institution): LOXO, Macrogenics, Menarini, Merck Serono, Merus, Millenium, Rigontec, Tahio, Tesaro; Advisory/Consultancy: Janssen-Cilag; Advisory/Consultancy: Seattle Genetics; Advisory/Consultancy: Pierre Fabre; Advisory/Consultancy: Cerulean Pharma; Advisory/Consultancy: EUSA; Advisory/Consultancy: Celgene; Full/Part-time employment, Officer/Board of Directors: START. All other authors have declared no conflicts of interest.