BGB-A317 is a humanized IgG4 anti-PD-1 mAb that blocks PD-L1/L2 binding to PD-1 restoring T-cell-mediated tumor inhibition. The Fc-hinge region has been engineered to preclude FcγR1-mediated binding to macrophages/myeloid-derived suppressor cells (MDSCs). Upregulation of PD-1/L1 and predominance of macrophages and MDSCs have been reported in GC and EC supporting the rationale of evaluating BGB-A317 in pts with GC or EC.
This ongoing, open-label, dose-escalation/expansion study is being conducted to evaluate the safety, tolerability and anti-tumor activity of BGB-A317 in pts with advanced solid tumors. Pts with histologically confirmed advanced GC or EC were eligible and treated with BGB-A317 at 2 mg/kg or 5 mg/kg every two weeks (Q2W) or Q3W. Adverse events (AEs) were assessed per NCI-CTCAE v4.03 and tumor assessments were performed approximately every two months via RECIST v1.1.
As of 6 MAR 2017, 55 pts [median age 62 yrs (22-81)] with recurrent/refractory GC (n = 28) or EC (n = 27) were treated. Most were Caucasian (n = 36) and all pts had received ≥1 prior line of anti-cancer treatment. Median treatment duration was 51 days (5–363); 19 pts remain on study. The most common treatment-emergent AEs were fatigue (n = 11), nausea (n = 9) and dysphagia (n = 8); 46% pts experienced AEs ≥Grade (Gr) 3 but none were treatment related. One serious AE (diarrhea [Gr 2]) was considered related to treatment by investigators. Of the 47 evaluable pts, the disease control rate, defined as the proportion of pts who achieved complete or partial response (CR or PR) or stable disease (SD), is 32%. PRs have been reported in 3 pts (GC = 2; EC = 1) with duration of responses being 96, 125 and 188 days respectively, 2 pts are still on treatment; 5 initial documentations of PRs awaiting confirmation (GC, n = 2; EC, n = 3) have been reported in 12 pts with SD (GC = 5; EC = 7).
BGB-A317 appears to be generally well tolerated in pts with recurrent/refractory GC or EC. The preliminary safety profile and anti-tumor activity appear to be consistent with other checkpoint inhibitors and support continued exploration and development of BGB-A317 in pts with advanced GC or EC.
Clinical trial identification
NCT02407990, March 26, 2015
Legal entity responsible for the study
J. Desai: Honoraria: Bayer, Merck Serono, Novartis. Consulting or advisory role: Amgen, Bayer, Bionomics, Circadian Technologies, Merck Serono, Norvartis. Research funding: GlaxoSmithKline (Inst), Roche-Genentech (Inst), Ventana Medical Systems (Inst). B. Markman: Personal fees from BeiGene during the conduct of the study. V. Atkinson: Honoraria: Bristol-Myers Squibb; MSD; Novartis. Consulting/advisory role: Bristol-Myers Squibb; MSD; Novartis. Travel, accommodations, expenses: Bristol-Myers Squibb; MSD; Novartis. A. Zhu: Research Funding: Lilly (Inst). J. Song: Employee of BeiGene USA, Inc. Q. Qi: Employee of Beigene (Beijing) Co. Ltd. A. Kang: BeiGene employee. All other authors have declared no conflicts of interest.