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.
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.
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.
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 and medical writing assistance were provided by Regina Switzer, PhD (SuccinctChoice Medical Communications, Chicago, IL).
NCT02407990.
BeiGene, Ltd.
BeiGene, Ltd.
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.