The primary purpose of this study is to establish the maximum tolerated dose (MTD) and/or recommended dose for expansion (RDE) of PDR001 when administered in combination with platinum-doublet chemotherapy and other immunooncology agent(s) in treatment naive patients with PD-L1 unselected, advanced NSCLC, and to estimate the preliminary anti-tumor activity in this patient population.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
111
Powder for solution for infusion
Intravenous infusion
Intravenous infusion
Highlands Oncology Group
Fayetteville, Arkansas, United States
Dose Limiting Toxicities (DLTs) during the first 6 weeks of therapy
A dose-limiting toxicity (DLT) is defined as an adverse event or abnormal laboratory value assessed as unrelated to disease, disease progression, inter-current illness, or concomitant medications that occurs within the first 42 days
Time frame: 42 days
Overall response rate (ORR) per local investigator assessment for groups A, B and C
ORR is defined as the proportion of patients with best overall response (BOR) of complete response (CR) or partial response (PR), as per RECIST 1.1 and local investigator assessment for groups A, B and C
Time frame: From baseline up to approximately 28 months
Overall Response Rate (ORR) per local investigator assessment for group E
ORR is defined as the proportion of patients with BOR of CR or PR, as per RECIST 1.1 and local investigator assessment for group E
Time frame: Up to approximately 28 months
Progression Free Survival (PFS) per Investigator
PFS is defined as the time from the date of start of treatment to the date of the first documented progression or death due to any cause, as per RECIST 1.1 and local investigator assessment
Time frame: From start of treatment to the date of the first documented progression or death due to any cause, whichever comes first, assessed up to approximately 28 months
Disease Control Rate (DCR) per Investigator
DCR is the proportion of patients with a BOR of CR or PR or stable disease (SD), as per RECIST 1.1 and local investigator assessment.
Time frame: Up to approximately 28 months
Duration of Response (DOR) per Investigator
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Intravenous infusion
Intravenous infusion
Intravenous infusion
Subcutaneous injection
UCLA Santa Monica Hematology / Oncology SC-2
Santa Monica, California, United States
Stanford Cancer Center SC
Stanford, California, United States
Henry Ford Health System SC
Detroit, Michigan, United States
Washington University School of Medicine SC
St Louis, Missouri, United States
Novartis Investigative Site
Leuven, Belgium
Novartis Investigative Site
Roeselare, Belgium
Novartis Investigative Site
Toronto, Ontario, Canada
Novartis Investigative Site
Prague, Czechia
Novartis Investigative Site
Lyon, France
...and 13 more locations
DOR is defined by responders as the time between the date of first documented response (CR or PR) and the date of first documented progression (RECIST 1.1 and local investigator assessment) or death due any cause
Time frame: From date of first documented response to the first documented progression or death due to any cause, whichever comes first, assessed up to approximately 28 months
Time to Response (TTR) per Investigator
TTR is defined as the time from the date of start of treatment to the first documented response of either CR or PR as per RECIST 1.1 and local investigator assessment
Time frame: From start of treatment to the date of the first documented reponse (CR or PR), assessed up to approximately 28 months
Overall survival (OS)
OS is defined as the time from date of start of treatment to date of death due to any cause.
Time frame: from date of start of treatment to date of death due to any cause (assessed up to approximately 3.5 years)
Trough plasma Concentration (Ctrough) of PDR001
Blood samples will be collected at indicated time points for pharmacokinetic analysis.
Time frame: Pre-infusion on Day 1 of Cycle 1 to 4 of induction phase; pre-infusion on Day 1 of Cycle 1 to 4, 6, 8 and every 6 cycle afterwards of maintenance phase; Cycle = 21 Days
Trough plasma Concentration (Ctrough) of chemotherapy
Blood samples will be collected at indicated time points for pharmacokinetic analysis. Ctrough will be assessed for all chemotherapy agents: cysplatin, pemetrexed, carboplatin and gemcitabine
Time frame: Pre-infusion on Day 1 of Cycle 1, 3 and 4 of induction phase; Cycle = 21 Days
Trough plasma Concentration (Ctrough) of canakinumab
Blood samples will be collected at indicated time points for pharmacokinetic analysis.
Time frame: Pre-infusion on Day 1 of Cycle 1, 3 and 4 of induction phase; Cycle = 21 Days
PDR001 Antidrug antibodies (ADA) prevalence at baseline
Blood samples will be collected at indicated time points for immunogenicity analysis.
Time frame: Baseline
Canakinumab ADA prevalence at baseline
Blood samples will be collected at indicated time points for immunogenicity analysis.
Time frame: Baseline
PDR001 ADA incidence during treatment
Blood samples will be collected at indicated time points for immunogenicity analysis.
Time frame: Pre-infusion on Day 1 of Cycle 1 to 4 of induction phase, pre-infusion on Day 1 of Cycle 1, 2, 3, 4, 6, 8 and every 6 cycle afterwards of maintenance phase, end of treatment and 30 and 150-day post-treatment
Canakinumab ADA incidence during treatment
Blood samples will be collected at indicated time points for immunogenicity analysis.
Time frame: Pre-infusion on Day 1 of Cycle 1 and 4 of induction phase, pre-infusion on Day 1 of Cycle 6, 14 and 20 of maintenance phase, end of treatment and 30 and 150-day post-treatment
Incidence of Adverse Events (AEs)
Incidence of AEs (CTCAE v4.03)
Time frame: through study completion, up to approximately 3.5 years