The purpose of this "first-in-human" study of PDR001 is to characterize the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and antitumor activity of PDR001 administered i.v. as a single agent to adult patients with solid tumors. By blocking the interaction between PD-1 and its ligands, PD-L1 and PD-L2, PDR001 inhibits the PD-1 immune checkpoint, resulting in activation of an antitumor immune response by activating effector T-cells and inhibiting regulatory T-cells. This study has been designed as a phase I/II, multi-center, open-label study starting with a phase I dose escalation part followed by a phase II part. PDR001 will be administered every 2 weeks until patient experiences unacceptable toxicity, progressive disease per immune related Response Criteria (irRC) and/or treatment is discontinued at the discretion of the investigator or the patient.
Name: PDR001
Description: anti-PD1 antibodyType: Biologicalpatients with solid tumors Selected tumor types
Description: To estimate the recommended phase 2 dose (RP2D) and/or the maximum tolerated dose (MTD) for PDR001
Measure: Part l: The exposure (AUC(0-336h)) after first dose of treatment Time: First 28 days of treatmentDescription: To estimate the RP2D and/or the MTD for PDR001
Measure: Part l: Incidence of dose limiting toxicities (DLTs) Time: First 28 days of treatmentDescription: As per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 - to estimte the anti-tumor activity of PDR001. Each cycle = 28 days
Measure: Part ll: Overall response Rate (ORR) Time: when all patients have completed at least 6 cycles of treatment or discontinued treatment. An average of 1 year duration is expected.Description: Safety as assessed by Incidence and severity of adverse events (AEs) and serious adverse events (SAEs), including changes in laboratory parameters, vital signs and electrocardiograms (ECGs) Tolerability as assessed by dose interruptions, reductions and dose intensity
Measure: Safety and Tolerability as assessed by incidence and severity of adverse events, dose interruptions, reductions and dose intensity Time: continuously during study until 30 days after post study treatmentDescription: To assess emergence of anti-PDR001 antibodies following one or more intravenous (i.v.) infusions of PDR001. Each cycle = 28 days; End of treatment = expected to be in average 1 year after the start of study treatment
Measure: Presence and/or concentration of anti-PDR001 Time: Cycle 1 day 1; Cycle 2 day 1; Cycle 3 day 1; Cycle 4 day 1; Cycle 5 day 1; Cycle 6 day 1; End of Treatment.Description: Preliminary antitumor activity of PDR001
Measure: Overall Response Rate (ORR) - Phase l only Time: every 8 weeks until cycle 11 and then every 12 weeks from the start of study until end of disease progression follow-up. An average of 1 year duration is expected.Description: Preliminary antitumor activity of PDR001
Measure: Progression Free Survival (PFS) - Phase l/ll Time: every 8 weeks until cycle 11 and then every 12 weeks from the start of study until end of disease progression follow-up. An average of 1 year duration is expected.Description: Preliminary antitumor activity of PDR001
Measure: Duration of Response (DOR) - Phase l/ll Time: every 8 weeks until cycle 11 and then every 12 weeks from the start of study until end of disease progression follow-up. An average of 1 year duration is expected.Description: Preliminary antitumor activity of PDR001
Measure: Disease Control Rate (DCR) - Phase l/ll Time: every 8 weeks until cycle 11 and then every 12 weeks from the start of study until end of disease progression follow-up. An average of 1 year duration is expected.Description: Preliminary antitumor activity of PDR001
Measure: Overall Response Rate (ORR) per immune related Response Criteria - Phase ll only Time: every 8 weeks until cycle 11 and then every 12 weeks from the start of study until end of disease progression follow-up. An average of 1 year duration is expected.Description: e.g., AUC, Cmax, Tmax, half-life to characterize the pharmacokinetic profile of PDR001. End of treatment = expected to be in average 1 year after the start of study treatment
Measure: Composite Serum pharmacokinetics (PK) parameters Time: cycles 1 days 1, 2, 3, 4, 8, 11, 15. Cycle 2 day 1. Cycle 3 days 1, 2, 3, 4, 8, 11, 15. Cycle 4 day 1, Cycle 5 day 1, Cycle 6 day 1, End of Treatment.Description: To characterize the pharmacokinetic profile of PDR001. End of treatment = expected to be in average 1 year after the start of study treatment
Measure: Serum concentration vs. time profiles Time: cycles 1 days 1, 2, 3, 4, 8, 11, 15. Cycle 2 day 1. Cycle 3 days 1, 2, 3, 4, 8, 11, 15. Cycle 4 day 1, Cycle 5 day 1, Cycle 6 day 1, End of Treatment.Allocation: Non-Randomized
Single Group Assignment
There is one SNP
Only patients with EGFR mutation-negative tumor are eligible (defined as negative for exon 19 deletions and for the L858R mutation in EGFR at a minimum; however, if more extensive EGFR mutation testing has been performed, the tumor must not harbor any known activating EGFR mutations in Exons 18-21 in order to be considered EGFR mutation-negative). --- L858R ---