920PFirst report of efficacy and safety from a phase II trial of tislelizumab, an anti-PD-1 antibody, for the treatment of PD-L1+ locally advanced or metastatic urothelial carcinoma (UC) in Asian patients

Abstract Background Tislelizumab, an investigational anti-PD-1 antibody, was engineered to minimize binding to FcγR on macrophages in order to abrogate antibody-dependent phagocytosis, a mechanism of T-cell clearance and potential resistance to anti-PD-1 therapy. Previous reports showed tislelizumab was generally well tolerated and had antitumor activity in patients (pts) with advanced solid tumours, including UC. Methods This phase 2 clinical trial (CTR20170071) assessed the safety, tolerability, and efficacy of tislelizumab (200 mg Q3W) in Asian pts with PD-L1+ UC previously treated with ≥1 platinum-containing therapy. Prior treatment with a PD-(L)1 inhibitor was not allowed. During screening, archival tissue or fresh biopsy from all pts was sent to a central laboratory for PD-L1 testing via the VENTANA SP263 IHC assay. Patients were considered PD-L1+ if ≥ 25% of tumor or immune cells had PD-L1 expression. The primary efficacy endpoint was ORR (RECIST v1.1), assessed by an independent review committee (IRC). Secondary efficacy endpoints included DoR, PFS, and OS; AE incidence and severity were secondary safety endpoints. Results Between 04 Jul 2017 and 28 Feb 2019, 113 pts received tislelizumab for a median of 15 weeks and were followed up for a median of 8 mo. Urinary bladder (n = 51) and renal pelvis (n = 31) were common primary tumor sites. Of 104 evaluable pts, a confirmed objective response was observed in 24 pts (ORR=23%, 95% CI: 15.4, 32.4), including 8 CR and 16 PR per IRC assessment. Median DoR per IRC was not reached at the time of protocol-defined analysis; 19/24 (79%) responders had ongoing responses at data cutoff. Median PFS and OS were 2.1 and 9.8 mo, respectively. Anemia (27%), decreased appetite (19%), and pyrexia (17%) were the only TRAEs occurring in > 15% of pts; anemia (7%) was the only grade 3-4 TRAE occurring in ≥ 5% pts. Four pts experienced a grade 5 AE considered related to disease progression but also possibly related to treatment (hepatic failure, n = 2; respiratory arrest, n = 1; renal impairment, n = 1). Conclusions Tislelizumab was generally well tolerated and demonstrated clinical activity in pts with PD-L1+ UC. Clinical trial identification CTR20170071. Editorial acknowledgement Stephan Lindsey, PhD, at OPEN Health Medical Communications (Chicago, IL). Legal entity responsible for the study BeiGene, Ltd. Funding BeiGene, Ltd. Disclosure X. Qiu: Full / Part-time employment: BeiGene. L. Zhang: Full / Part-time employment: BeiGene. W. Shen: Full / Part-time employment: BeiGene. All other authors have declared no conflicts of interest.