Background: 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 limiting toxicity was reported. The most common AEs included: nausea, fatigue, anemia, diarrhea, dyspnea, vomiting, abdominal pain and headache. Three cases of hypothyroidism suspected to be related to PDR001 were reported. A single case of grade 3 autoimmune colitis was the only serious AE suspected to be related to PDR001. Approximately dose-proportional increases in exposure were observed from 1–10 mg/kg. PDR001 achieves an AUC_0-336h of approximately 1000 µg*day/mL at cycle 3 with 3 mg/kg Q2W or 5 mg/kg Q4W. Based on the population PK analysis, a flat dose of 400 mg Q4W is predicted to achieve mean steady-state C_trough concentrations of approximately 31 µg/mL (90% CI: 22–42 µg/mL), which exceeds the ex vivo EC₅₀ for PD-1 blockade. The recommended phase 2 dose (RP2D) for PDR001 is therefore 400 mg Q4W. An alternative dosing regimen of 300 mg Q3W is expected to achieve similar exposure to 400 mg Q4W. Conclusions: Based on the preliminary data, PDR001 was well tolerated with a safety profile similar to those of other marketed anti-PD-1 antibodies. Based on the available PK and safety data described above, the RP2D of PDR001 has been declared as 400 mg i.v. Q4W, or 300 mg i.v. Q3W as an option for more convenient scheduling in combination treatment regimens. Clinical trial information: NCT02404441