A first-in-human phase I study of the anti-PD-1 antibody PDR001 in patients with advanced solid tumors.

3060Background: PDR001 is a humanized anti-PD-1 IgG4 antibody that blocks the binding of PD-L1 and PD-L2 to PD-1. PDR001 binds to PD-1 with high affinity and inhibits the biological activity of PD-1. Methods: Phase I dose escalation study of PDR001 given i.v. Q2W or Q4W to adult patients with advanced solid tumors. A Bayesian linear model estimating the dose–exposure relationship and a Bayesian logistic regression model with overdose control were used to guide dose escalation. Preliminary population PK analysis was conducted to estimate PK parameters and assess the impact of weight as a covariate on clearance and volume of distribution. Results: In the dose escalation part of the study, 58 patients have been treated with PDR001 at 5 dose levels and schedules: 1 mg/kg Q2W (16 pts); 3 mg/kg Q2W (15), 10 mg/kg Q2W (11), 3 mg/kg Q4W (6) and 5 mg/kg Q4W (10). 27/58 patients have been treated for > 3 cycles (cycle length: 28 days), and 27/58 remain on treatment at the time of abstract preparation. No dose limit...