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: 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: 8 monthsDescription: To estimate the RP2D and/or the MTD for PDR001
Measure: Part l: Incidence of dose limiting toxicities (DLTs) Time: 8 monthsDescription: 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: 61 monthsDescription: 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: 42 monthsDescription: Preliminary antitumor activity of PDR001
Measure: Overall Response Rate (ORR) - Phase l only Time: 27 monthsDescription: Preliminary antitumor activity of PDR001
Measure: Progression Free Survival (PFS) - Phase l/ll Time: 61 monthsDescription: Preliminary antitumor activity of PDR001
Measure: Duration of Response (DOR) - Phase l/ll Time: 61 monthsDescription: Preliminary antitumor activity of PDR001
Measure: Disease Control Rate (DCR) - Phase l/ll Time: 61 monthsDescription: Preliminary antitumor activity of PDR001
Measure: Overall Response Rate (ORR) per immune related Response Criteria - Phase ll only Time: 61 monthsDescription: Characterize the pharmacokinetic (PK) profile of PDR001
Measure: Serum pharmacokinetic (PK) parameter AUCs Time: 37 monthsDescription: Characterize the pharmacokinetic (PK) profile of PDR001
Measure: Serum Pharmacokinetic (PK) parameter Cmax Time: 37 monthsDescription: Characterize the pharmacokinetic (PK) profile of PDR001
Measure: Serum Pharmacokinetic (PK) parameter Tmax Time: 37 monthsAllocation: 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 ---