The purpose of this study is to determine the safety, tolerability, feasibility and preliminary efficacy of the administration of PBF-509 (Adenosine A2a receptor antagonist) as single agent or in combination with PDR001 (programmed cell death 1 receptor antibody (PD-1 Ab)) to NSCLC patients.
Name: PBF-509_80 mg
Description: PBF-509: 80 mg, PO, twice daily (BID)Type: DrugPBF-509_80 mg
Name: PBF-509_160 mg
Description: PBF-509: 160 mg, PO, twice daily (BID)Type: DrugPBF-509_160 mg
Name: PBF-509_320 mg
Description: PBF-509: 320 mg, PO, twice daily (BID)Type: DrugPBF-509_320 mg
Name: PBF-509_640 mg
Description: PBF-509: 640 mg, PO, twice daily (BID)Type: DrugPBF-509_640 mg
Name: Combo PBF-509 (160 mg) + PDR001
Description: Drug 1: PDR001 administered intravenously. Drug 2: PBF-509 administered orallyType: DrugPBF509_160 mg +PDR001
Name: Combo PBF-509 (320 mg) + PDR001
Description: Drug 1: PDR001 administered intravenously. Drug 2: PBF-509 administered orallyType: DrugPBF509_320 mg+PDR001
Name: Combo PBF-509 (640 mg) + PDR001
Description: Drug 1: PDR001 administered intravenously. Drug 2: PBF-509 administered orallyType: DrugPBF509_640 mg +PDR001
Name: RP2D (PBF-509+PDR001)_immuno naïve
Description: Drug 1: PDR001 administered intravenously. Drug 2: PBF509 administered orallyType: DrugRP2D (PBF-509+PDR001)_immuno naïve
Name: Experimental: RP2D (PBF-509+PDR001)_immuno treated
Description: Drug 1: PDR001 administered intravenously. Drug 2: PBF509 administered orallyType: DrugRP2D (PBF-509+PDR001)_immuno treated
Description: The MTD evaluation will be based on the DLT Evaluable Population which includes all patients enrolled in the dose-escalation portion of the trial, who receive the protocol-assigned treatment with PBF-509 and complete the safety follow-up through the DLT evaluation period, or experience a DLT during the DLT evaluation period.
Measure: Maximum Tolerated Dose (MTD) of PBF-509 as single agent Time: 28 daysDescription: The MTD evaluation will be based on the DLT Evaluable Population which includes all patients enrolled in the dose-escalation portion of the trial, who receive the protocol-assigned treatment with PDR001 and PBF-509 and complete the safety follow-up through the DLT evaluation period, or experience a DLT during the DLT evaluation period.
Measure: Maximum Tolerated Dose (MTD) of the combination (PBF-509+PDR001) treatment Time: 56 daysDescription: The parameter will be calculated from plasma samples collected at days 1 and 8 after drug administration. It will consist in the time (in minutes) to reach the maximum "PBF-509" concentration in plasma samples of patients after oral administration of PBF-509.
Measure: Time to PBF-509 peak concentration in plasma "Tmax" Time: 8 daysDescription: The parameter will be calculated from plasma samples collected at days 1 and 8 after drug administration. It will consist in the time (in minutes) to reach the maximum "PBF-509" concentration in plasma samples of patients during a dosing interval at steady state.
Measure: Time to PBF-509 peak concentration in plasma at steady state "Tmax,ss" Time: 8 daysDescription: The parameter will be calculated from plasma samples collected at days 1 and 8 after drug administration. It will consist in the maximum plasma concentration (ng/mL) of PBF-509 observed after administration.
Measure: PBF-509 peak concentration in plasma "Cmax" Time: 8 daysDescription: The parameter will be calculated from plasma samples collected at days 1 and 8 after drug administration. It will consist in the maximum plasma concentration (ng/mL) of PBF-509 observed during a dosing interval at steady state.
Measure: PBF-509 peak concentration in plasma at steady state"Cmax,ss" Time: 8 daysDescription: The parameter will be calculated from plasma samples collected at days 1 and 8 after drug administration. It will consist in the area under the concentration-time curve from zero up to ∞ with extrapolation of the terminal phase. "AUC(0-inf)" will be given in Amount·time/ volume units
Measure: The area under PBF-509 plasma concentration-time curve to infinite time "AUC(0-inf)" Time: 8 daysDescription: The parameter will be calculated from plasma samples collected at days 1 and 8 after drug administration. It will consist in the area under the concentration-time curve from zero up to a definite time t. "AUC(0-t)" will be given in Amount·time/ volume units.
Measure: The area under PBF-509 plasma concentration-time curve up to time 't' "AUC(0-t)" Time: 8 daysDescription: The parameter will be calculated from plasma samples collected at days 1 and 8 after drug administration. It will consist in the area under the concentration-time curve over the dosing interval. "AUC(0-τ)" will be given in Amount·time/ volume units.
Measure: The area under PBF-509 plasma concentration-time curve over the dosing interval "AUC(0-τ)" Time: 8 daysDescription: The parameter will be calculated from plasma samples collected at days 1 and 8 after drug administration. It will consist in the terminal half-life of PBF-509 in plasma. "t½" will be given in hours (h)
Measure: PBF-509 half-life in plasma " t½" Time: 8 daysDescription: The parameter will be calculated from plasma samples collected at days 1 and 8 after drug administration. It will consist in the apparent volume of distribution during terminal phase after oral / extravascular administration. "Vd/F" will be given in Volume or volume/kg units.
Measure: PBF-509 apparent volume of distribution following extravascular administration"Vd/F" Time: 8 daysDescription: The parameter will be calculated from plasma samples collected at days 1 and 8 after drug administration. It will consist in the apparent total plasma or serum clearance of drug after oral administration. "Cl/F" will be given in the Volume/ time or volume/ time/ kg units.
Measure: PBF-509 total body clearance following extravascular administration "Cl/F" Time: 8 daysDescription: The parameter will be calculated from plasma samples collected at days 1 and 8 after drug administration. It will consist in the accumulation ratio calculated from Cmax,ss at steady state and Cmax after single dosing.
Measure: The PBF 509 accumulation index "Rac" Time: 8 daysDescription: ORR: Response and progression will be evaluated in this study using the new international criteria proposed by the revised Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1). ORR is defined as confirmed complete response (CR) or partial response (PR) based on modified RECIST v1.1.
Measure: Efficacy as measured by Objective response rate (ORR) Time: 3 yearsDescription: The disease control rate (DCR) will be estimated considering the following variables: Complete response (CR), Partial response (PR) and stable disease (SD) as described by Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1). These variables will be assessed based on Imaging-based evaluation methods as chest x-ray, conventional computed tomography (CT) and magnetic resonance imaging (MRI) that will be performed every 2 cycles of 28 days administration
Measure: Efficacy as measured by Disease control rate (DCR) Time: 3 yearsDescription: Duration of response (DoR) is defined as the duration from the first documentation of OR to the first documented disease progression or death due to any cause, whichever occurs first.
Measure: Efficacy as measured by duration of response (DoR) Time: 3 yearsDescription: Progression-free survival (PFS) will be measured from the start of treatment until the documentation of disease progression or death due to any cause, whichever occurs first. For subjects who are alive and progression-free at the time of data cut-off for analysis, PFS will be censored at the last tumor assessment date.
Measure: Efficacy as measured by progression-free survival (PFS) Time: 3 yearsDescription: Overall survival (OS) will be determined as the time from the start of treatment until death due to any cause.
Measure: Efficacy as measured by overall survival (OS) Time: 3 yearsAllocation: Non-Randomized
Single Group Assignment
There is one SNP
2. Patients must previously have received at least one prior line of therapy for their disease 3. EGFR mutation with exon 19 deletion or L858R mutation (Exon 21) or ALK rearrangement positive must have failed prior TKI therapy 4. Able, willing to give written consent for available archival tumor samples (not mandatory) and tumor biopsies before and during protocol therapy (mandatory). --- L858R ---