Abstract 552P
Background
Tislelizumab, a clinical-stage anti-PD-1 antibody, was engineered to minimize binding to FcγR on macrophages to abrogate antibody-dependent phagocytosis, a mechanism of T-cell clearance and potential resistance to anti-PD-1 therapy. Initial reports from this phase I/II study (NCT04068519) showed single-agent tislelizumab was generally well tolerated and had antitumor activity in patients (pts) with advanced solid tumors; clinical effects and safety of long-term exposure (LTE; >12 mo) to tislelizumab are presented.
Methods
Eligible pts had histologically or cytologically confirmed advanced solid tumors and progressed on, or were intolerant to, their last standard antitumor treatment; pts receiving prior anti-PD-(L)1 therapy were ineligible. Treatment beyond progression was allowed. PD-L1 expression was assessed by the VENTANA PD-L1 (SP263) assay. Key endpoints included antitumor response, overall survival (OS), and safety/tolerability.
Results
As of 01 Dec 2019, of 300 enrolled pts, 70 had received tislelizumab for >12 mo (median age, 54 yr; ≥2 lines of prior systemic therapy, 49%). Median duration of treatment was 20.9 mo with 29 pts treated beyond progression. The most common tumor types of pts with LTE were NSCLC (n=16) and NPC (n=8). For all pts with LTE, ORR was 55.7%, with responses observed in both PD-L1 ≥10% and <10% pts (Table). With a median study follow-up of 24.7 mo, median duration of response and median OS were not reached. Commonly reported treatment-related adverse events (TRAEs) included increased ALT (n=24, 34.3%) and AST (n=22, 31.4%); TRAEs across the entire study were mostly of grade ≤2 severity. Three pts (4.3%) had TRAEs leading to treatment discontinuation; no pt reported a TRAE leading to death. Table: 552P
| Best overall response in patients with long-term exposure (>12 Months) to tislelizumab by PD-L1 status | ||||
| PD-L1 ≥10% (n=18) | PD-L1 <10% (n=45) | PD-L1 Missing (n=7) | Total (N=70) | |
| CR, n (%) | 0 (0) | 1 (2.2) | 0 (0) | 1 (1.4) |
| PR, n (%) | 10 (55.6) | 23 (51.1) | 5 (71.4) | 38 (54.3) |
| SD, n (%) | 6 (33.3) | 19 (42.2) | 1 (14.3) | 26 (37.1) |
| PD, n (%) | 2 (11.1) | 2 (4.4) | 1 (14.3) | 5 (7.1) |
| ORR, % (95% CI) | 55.6 (30.8, 78.5) | 53.3 (37.9, 68.3) | 71.4 (29.0, 96.3) | 55.7 (43.3, 67.6) |
Abbreviations: CI, Confidence interval; CR, complete response; ORR, objective response rate; PD, progressive disease; PR, partial response; SD stable disease.
Conclusions
Tislelizumab remained generally well tolerated with no new safety signals when administered for >12 mo and elicited durable responses in pts with a variety of tumor types, regardless of PD-L1 status.
Clinical trial identification
NCT04068519.
Editorial acknowledgement
Writing and editorial assistance was provided by Stephan Lindsey, and Elizabeth Hermans, PhD (OPEN Health Medical Communications, Chicago. IL), and funded by the study sponsor.
Legal entity responsible for the study
This study was sponsored by BeiGene, Ltd.
Funding
BeiGene, Ltd.
Disclosure
L. Shen: Full/Part-time employment: BeiGene, Ltd.. Y-L. Wu: Honoraria (self), Advisory/Consultancy: AstraZeneca; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Boehringer Ingelheim; Honoraria (self): Lilly; Honoraria (self): Pfizer; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Roche; Honoraria (self): Sanofi; Advisory/Consultancy: Merck. Q. Zhou: Honoraria (self): AstraZeneca; Honoraria (self): Roche. Y. Gao: Full/Part-time employment: BeiGene, Ltd.. S. Yang: Full/Part-time employment: BeiGene, Ltd.. Y. Li: Full/Part-time employment: BeiGene, Ltd.. J. Zhang: Full/Part-time employment: BeiGene, Ltd.. J. Guo: Advisory/Consultancy: MSD; Advisory/Consultancy: Roche; Advisory/Consultancy: Pfizer; Advisory/Consultancy: Bayer; Advisory/Consultancy: Novartis; Advisory/Consultancy: Simcere; Advisory/Consultancy: Shanghai Junshi Biosciences; Advisory/Consultancy: Oriengene; Advisory/Consultancy: Betta Pharmaceuticals Co.,Ltd.. All other authors have declared no conflicts of interest.