A First-In-Human Phase 1a Trial Of Sintilimab (Ibi308), A Monoclonal Antibody Targeting Programmed Death-1 (Pd-1), In Chinese Patients With Advanced Solid Tumors.

e15125 Background: Sintilimab (IBI308), a humanized IgG4 anti-PD-1 antibody, showed potent anti-tumor activity in preclinical models. This open label, first in human, dose escalation study evaluated tolerability, safety, pharmacokinetic (PK), pharmacodynamics and preliminary efficacy in patients (pts) with advanced solid tumors. Methods: “3+3” design was used in this trial during dose escalation: 1mg/kg, 3mg/kg and 200mg (1:1 randomization) and 10mg/kg. After 28 days of dose limiting toxicity (DLT) observation, pts would repeat doses every 3 weeks for 200 mg level and every 2 weeks for the other dose levels. PK and pharmacodynamics were assessed across different dose levels. Adverse events (AEs) were graded by NCI CTCAE v4.03. Tumors were assessed by RECIST 1.1 and irRECIST every 9 weeks. Cut-off date for analysis was Dec 9, 2017. Results: In total, 12 pts with advanced solid tumor (n = 3 for each dose level) received at least one dose of sintilimab (the median exposure is 13.8 weeks). No DLTs occurred, the maximum tolerated dose (MTD) was not reached. Most common treatment-related AEs were fever (3/12, all G1), thyroid dysfunction (3/12, all G1), serum bilirubin elevation (3/12, all G1) and pneumonitis (3/12, G1, 2 and 3). Four pts experienced ≥G3 treatment-related AE, including lung infection, pneumonitis, respiratory failure, lipase increased and amylase increased. All AEs resolved after management. No treatment-related death occurred. Sintilimab showed linear PK prolife (1-10mg/kg) with PD-1 receptor occupancy > 95% across 4 does levels. Eleven pts received response evaluation, 2 confirmed PR (hepatocellular carcinoma and neuroendocrine tumor) with duration of response of 9.5 and 5.7 months respectively, and 2 SD (neuroendocrine tumor). One PD (hepatocellular carcinoma) achieved irPR after 11 months. 200 mg Q3W was recommended for the further study. Conclusions: Sintilimab is well tolerated and the preliminary efficacy results are promising. Upcoming safety and efficacy data on expansion cohorts will be presented. Clinical trial information: NCT02937116.