BGB-A317 is a humanized IgG4 anti-PD-1 mAb that blocks PD-L1/PD-L2 binding to PD-1 restoring T-cell mediated tumor response. The Fc-hinge region has been engineered to preclude FcγR1 mediated binding to macrophages/myeloid-derived suppressor cells, a potential mechanism of PD-1 bound T-cell clearance. Regulatory Foxp3+ T-cells and PD-1+T-cell infiltration in the tumor microenvironment have been reported in HNSCC supporting the rationale for evaluation of BGB-A317 in pts with HNSCC. Here we present the preliminary results from a subset of pts with HNSCC treated with BGB-A317.
This ph 1, open-label, multi-center, dose-escalation/expansion study was conducted to evaluate the safety, tolerability, and anti-tumor activity of BGB-A317 in pts with advanced solid tumors. Pts with histologically confirmed advanced HNSCC who progressed following standard of care treatment were eligible to receive BGB-A317 administered at a dose of 5 mg/kg Q3W. Adverse events (AEs) were assessed per NCI-CTCAE v4.03. Tumor assessments were performed Q9W per RECIST v1.1.
As of 6 Mar 2017, 18 pts with recurrent HNSCC were enrolled (median age, 63 years [25-78]). Most pts were male (89%), Caucasian (67%) and had received ≥2 prior lines of anti-cancer treatment. The median treatment duration for BGB-A316 was 104 days (30-245); 7 pts remain on study. Most treatment-emergent AEs were Grade (Gr) 1/2 in severity and the more common AEs were fatigue (n = 6), constipation (n = 3) and ear discomfort (n = 3). Eleven unique AEs ≥Gr 3 were reported in 7 pts: dysphagia, nausea salivary gland enlargement, dyspnea, pleuritic pain, aspiration pneumonia, infection-related COPD exacerbation, parotitis, ocular hyperemia, and wound hemorrhage. A partial response (PR) has been confirmed in 1 pt, and 8 pts have stable disease (SD,) including 2 unconfirmed PRs. The disease control rate, defined as the proportion of pts who have achieved CR, PR and SD, is 50%.
BGB-A317 appears to be well tolerated in pts with recurrent HNSCC. The preliminary safety profile and anti-tumor activity support continued investigation of BGB-A317 in this setting.
Clinical trial identification
NCT02407990, March 26, 2015
Legal entity responsible for the study
L. Horvath: Clinical trials agreement with budget from Beigene, during the conduct of the study; J. Desai, S. Sandhu: 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). A.G. Hill: Research funding, Stock and Other Ownership Interests: Tasman Oncology. Travel Accommodations, Expenses: Bristol-Myers Squibb. B. Markman: Personal fees from Beigene during the conduct of the study. Z. Chen, J. Hou: Employee of BeiGene Ltd. X. Tan: Employee of BeiGene (Beijing) Co. Ltd. All other authors have declared no conflicts of interest.