A phase Ia/Ib trial of tislelizumab, an anti-PD-1 antibody (ab), in patients (pts) with advanced solid tumors
Authors: S. Deva, J.-S. Lee, C.-C. Lin, C.-J. Yen, M. Millward, Y. Chao, B. Keam, M. Jameson, M.-M. Hou, Y.-K. Kang, B. Markman, C.-H. Lu, K.-M. Rau, K.-H. Lee, L. Horvath, M. Friedlander, A. Hill, J. Wu, J. Hou, J. Desai
Journal: Annals of Oncology (2018)

Background: Tislelizumab, a humanized IgG4 monoclonal Ab with high affinity and specificity for PD-1, was engineered to minimize binding to FcγR on macrophages, thus abrogating antibody-dependent phagocytosis, a mechanism of T-cell clearance and potential resistance to anti-PD-1 therapy. Previous reports from this first-in-human study (NCT02407990), and other early phase studies, suggested tislelizumab was generally well tolerated and had antitumor activity in pts with advanced solid tumors. Here we report the effects of tislelizumab in a subset of pts enrolled in phase 1A/1B. Methods: Eligible patients with advanced esophageal [EC], gastric [GC], hepatocellular [HCC], and non-small cell lung [NSCLC] cancers were treated with tislelizumab 2 or 5 mg/kg every 2 wks or 3 wks (Q3W); 97% received 5mg/kg Q3W. Adverse events (AEs) were assessed per NCI-CTCAE 4.03 criteria and tumor assessments performed every 9 wks using RECIST v1.1. Results: Of the 207 pts (EC = 54; GC = 54; HCC = 50; NSCLC = 49), 114 were male, 111 were Asian, 78 were Caucasian and all but one received ≥1 prior anticancer therapy. Treatment-related AEs (TRAEs) occurring in ≥5% of pts were fatigue (8.7%), decreased appetite (6.8%), rash (6.8%), hypothyroidism (6.3%), and nausea (6.3%). Grade ≥3 TRAEs occurring in ≥2 pts were pneumonitis (n = 3), elevated AST (n = 3), and elevated ALT (n = 2). Grade 5 TRAEs occurred in two pts: pneumonitis in a pt with NSCLC with compromised pulmonary function and acute hepatitis in a pt with HCC with rapidly progressing disease. As of 27 Apr 2018, a total of 23 pts remained on study treatment; median duration of study follow-up ranged from 4.9–9.9 mo. Responses in each tumor type are presented in the table.Table70OBest Overall Response, ConfirmedEC N = 53GC N = 52HCC N = 49NSCLC N = 44CR, n1000PR, n5766SD, n1491923PD, n25312312Not evaluable/missing, n8513ORR, % (95% CI)11.3 (4.3, 23.0)13.5 (5.6, 25.8)12.2 (4.6, 24.8)13.6 (5.2, 27.4)DCR, % (95% CI)37.7 (24.8, 52.1)30.8 (18.7, 45.1)51.0 (36.3, 65.6)65.9 (50.1, 79.5)ORR = CR + PR; DCR = CR + PR + SD. Abbreviations: CI, confidence interval; CR, complete response; DCR, disease control rate; ORR, objective response rate; PD, progressive disease; PR, partial response; SD, stable disease. Open table in a new tab ORR = CR + PR; DCR = CR + PR + SD. Abbreviations: CI, confidence interval; CR, complete response; DCR, disease control rate; ORR, objective response rate; PD, progressive disease; PR, partial response; SD, stable disease. Conclusions: Tislelizumab was generally well tolerated and antitumor activity was observed in each tumor type. Tislelizumab, as monotherapy and in combination, is being evaluated in multiple phase 2 and phase 3 studies. Editorial acknowledgement: Medical writing and editorial assistance was 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. Deva: Travel, accomodations, expenses: Roche. M. Millward: Research funding to institution: Beigene; Consulting or advisory role: AstraZeneca, Roche, BMS, MSD; Travel, accomodations, expenses: Roche, BMS, MSD. M. Jameson: Research funding: Beigene, Merck, Dynavaz, Pfizer to institution; Travel, accomodations, expenses: Merck. Y. Kang: Research funding: Roche; Consulting or advisory roles: Novartis, Roche, BMS, Ono, Blueprint, Daehwa. B. Markman: Consulting or advisory role: Novartis. L. Horvath: Speakers bureau: Janssen-Cilag; Research funding: Astellas. M. Friedlander: Honoraria: AstraZeneca, MSD; Consulting or advisory role: AstraZeneca, MSD; Research funding: BeiGene (Inst). A. Hill: Employment, stock, other ownership interests, research funding: Tasman Oncology; Travel, accommodations, expenses: Bristol-Myers Squibb. J. Wu, J. Hou: Employee of 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.