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 OC supporting the rationale of evaluating BGB-A317 in pts with OC.
An open-label, multi-center, 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 OC were eligible and treated at different dose levels (0.5, 2, 5, 10 mg/kg intravenously [IV] every 2 weeks [Q2W] in dose escalation, or at 2 or 5 mg/kg IV Q2W or Q3W, or 200 mg IV Q3W in dose expansion, or 5 mg/kg IV Q3W in indication expansion). Tumor assessments, including CA125, occurred approximately every 2 months and response was collected according to both RECIST 1.1 and GCIG criteria. Adverse events (AEs) were assessed per NCI-CTCAE v4.03.
As of 6 Mar 2017, 51 pts [median age 62 (19–80) yrs] with recurrent/refractory OC were enrolled. Most pts were Caucasian (88%), all had received ≥1 prior line of anti-cancer treatment (median 3 [1–12]). Median duration of treatment was 68 (22–446) days; 7 pts remain on study. The most common treatment-emergent AEs were nausea (37%), fatigue (28%), and abdominal pain (28%). 49% of pts experienced an AE ≥Grade (Gr) 3; stomatitis (n = 1) and diarrhoea (n = 1) were Gr 3 AEs considered treatment-related by investigators. Mucosal inflammation, pyrexia and colitis were serious AEs considered treatment-related by investigators (n = 1, each). Among 51 evaluable pts, the disease control rate is 43%; 2 PRs have been reported including 1 pt who remains on study and to date has achieved an 89% reduction in target lesions.
BGB-A317 appears to be generally well tolerated in pts with recurrent/refractory OC. The preliminary safety profile and anti-tumor activity are consistent with that observed with other checkpoint inhibitors and support continued investigation of BGB-A317.
Clinical trial identification
NCT02407990, March 26, 2015
Legal entity responsible for the study
T. Meniawy: Non-financial support and other from BeiGene during the conduct of the study; Non-financial support from Bristol-Myers Squibb outside the submitted work. 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). L. Horvath: Clinical trial agreement with budget from Beigene, during the conduct of the study; S. Sandhu: Honoraria: Bristol-Myers Squibb, Merck. Consulting or Advisory: Amgen. Z. Wu: Employee of Beigene USA, Inc. Z. Qin, K. Kang: Employee of BeiGene (Beijing) Co. Ltd. B. Markman: Personal fees from Beigene during the conduct of the study. All other authors have declared no conflicts of interest.