Background: BGB-A317 is a humanized IgG4 anti-PD-1 mAb with high specificity and affinity (K_D = 0.15 nM) for PD-1. It blocks PD-L1 and PD-L2 binding, and inhibits PD-1-mediated negative signaling in T-cell lines and tumor growth in a number of allogeneic xenograft models. Methods: A phase I, multicenter study was conducted to evaluate the safety, tolerability, pharmacokinetics (PK) and antitumor activity of BGB-A317 in patients (pts) with advanced solid tumors. A 3+3 dose escalation design was undertaken. Pts received escalating doses of BGB-A317 intravenously biweekly (Q2W). Additional pts were treated at 2 and 5 mg/kg either Q2W or Q3W to explore alternate schedules. Results: As of 15 Dec, 2015, 61 patients were treated across 4 dose-escalating cohorts of BGB-A317 Q2W (0.5 mg/kg, n = 3; 2 mg/kg, n = 6; 5 mg/kg, n = 6 and 10 mg/kg, n = 6) and 4 dose-expansion cohorts (2 mg/kg, Q2W, n = 20; 2 mg/kg, Q3W, n = 2; 5 mg/kg Q2W, n = 17 and 5 mg/kg, Q3W, n = 1). One DLT (1/6) of grade 3 colitis was observed in the 5 mg/kg Q2W cohort. Maximum tolerated dose was not reached. The most common treatment-emergent adverse events (AEs) were grade (G) 1-2 fatigue (25%), diarrhea (20%), nausea (16%), rash (13%), pruritus (11%) and abdominal pain (11%). Treatment–related G3 AEs included diabetic ketoacidosis (n = 1, 2 mg/kg Q2W), hypotension (n = 1, 2 mg/kg Q2W), colitis (n = 2, 5 mg/kg Q2W), elevated ALT (n = 1, 2 mg/kg Q2W), hyperglycaemia (n = 1, 2 mg/kg Q2W) and fatigue (n = 1, 5 mg/kg Q2W). PKs of BGB-A317 show dose-proportional exposure increase from 0.5 to 10 mg/kg Q2W after the single dose administration with the elimination half-life of 11 to 17 days. Among 39 evaluable pts to date (10 ovarian, 6 colorectal, 6 RCC, 4 cutaneous SCC, 3 mesothelioma, 2 cervical, and 1 each of 8 others), 3 pts have partial response (2 to be confirmed) (1 gastric, 1 RCC and 1 cervical) and a further 13 pts exhibit stable disease. All 3 responding pts remain on treatment, ranging from 13 to 23 weeks. Conclusions: BGB-A317 demonstrates a favorable safety profile with AEs in keeping with the class effect. PKs are linear and early promising anti-tumor activity has been observed. The expansion cohorts are ongoing and an expanded phase IB study in selected cancer types is planned. Clinical trial information: NCT02407990