Tislelizumab, an anti-PD-1 antibody, in patients with urothelial carcinoma (UC): Results from an ongoing phase I/II study

Background: Tislelizumab, a humanized IgG4 mAb with high affinity and specificity for PD-1, was engineered to minimize binding to FcɤR on macrophages, thus abrogating antibody-dependent phagocytosis, a potential mechanism of T-cell clearance and resistance to anti-PD-1 therapy. Previous reports from this first-in-human study (NCT02407990), and other early phase studies, suggest tislelizumab was generally well tolerated and had antitumor activity in pts with advanced solid tumors. Methods: Patients with UC received tislelizumab at doses of 2, 5, or 10 mg/kg Q2W or Q3W, and 200 mg Q3W. Tumor cell (TC) and immune cell (IC) PD-L1 expression were retrospectively assessed with the VENTANA PD-L1 (SP263) assay. Adverse events (AEs) were assessed per NCI-CTCAE 4.03 and tumor assessments were performed every 9 wks using RECIST v1.1. Results: A total of 17 pts with UC (median age, 71 yr [range 39–79]) received tislelizumab, the majority of which received 5 mg/kg Q3W (n = 11). All pts were Caucasian and 14 were male; median number of prior systemic anticancer therapies was 1 (range 0–4). Treatment-related AEs (TRAEs) occurring in ≥ 3 pts included fatigue (n = 5), infusion-related reaction (n = 3), and rash (n = 3). Grade ≥3 TRAEs were fatigue, hyperglycemia, and type 1 diabetes mellitus (T1DM; n = 1 each). Three pts experienced serious TRAEs (infusion-related reaction [n = 1], hyperglycemia and T1DM [n = 1], and pneumonitis [n = 1]). As of 27 Apr 2018, median duration of follow up was 8.8 mo (range 0.9–29.1) and 2 pts remained on treatment. All pts were evaluable for response. Confirmed CR (n = 1) and PR (n = 4) were observed; SD was achieved in 3 pts. ORR and DCR were 29% (95% CI 10.3, 55.9) and 47% (95% CI 22.9, 72.1), respectively. Sixteen samples were available for PD-L1 evaluation. Responses were observed in 4 (n = 1 CR; n = 3 PR) of 10 pts with PD-L1+ tumors (defined as ≥ 25% TC or IC expressing PD-L1 by IHC), while 1 (PR) in 6 pts with PD-L1– tumors responded. Conclusions: Tislelizumab was generally well tolerated in pts with UC and responses were observed in both PD-L1+ and PD-L1– diseases. Tislelizumab is currently being investigated in China as monotherapy for pts with PD-L1+ UC (CTR20170071). Editorial acknowledgement: Editorial and medical writing assistance were provided by Regina Switzer, PhD (SuccinctChoice Medical Communications, Chicago, IL). Clinical trial identification: NCT02407990. Legal entity responsible for the study: BeiGene, Ltd. Funding: BeiGene, Ltd. Disclosure: S. Sandhu: Honoraria: Amgen, Bristol-Myers Squibb, Merck; Consulting or advisory role: Amgen; Speakers' bureau: Bristol-Myers Squibb, Merck. A. Hill: Stock and other ownership interests: Tasman Oncology; Research funding: Tasman Oncology; Travel, accommodations, expenses: Bristol-Myers Squibb. H. Gan: Consulting or advisory role: AbbVie, Merck Serono; Speakers' bureau: Abbvie, Bristol-Myers Squibb, Ignyta; Research funding: AbbVie; Travel, accommodations, expenses: AbbVie, Ignyta, Merck Sharp & Dohme. M. Friedlander: Honoraria: AstraZeneca, MSD; Consulting or advisory role: AstraZeneca, MSD; Research funding: BeiGene (Inst). M. Voskoboynik: Travel, accommodations, expenses: Bristol-Myers Squibb. P. Barlow: Travel, accommodations, expenses: MSD, Roche.J. Song, Y. Zhang, L. Liang: Employee: BeiGene. J. Desai: Consulting or advisory role: Amgen, Beigene, Bionomics, Eisai, Lilly, Novartis; Research funding: Bionomics (Inst), GlaxoSmithKline (Inst), Novartis (Inst), Roche (Inst). All other authors have declared no conflicts of interest.