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PDR001 in Combination With Platinum-doublet Chemotherapy and Other Immunology Agents in PD-L1 Unselected, Metastatic NSCLC Patients

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ClinicalTrials.gov Identifier: NCT03064854
Recruitment Status : Completed
First Posted : February 27, 2017
Last Update Posted : September 13, 2021
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Tracking Information
First Submitted Date  ICMJE February 6, 2017
First Posted Date  ICMJE February 27, 2017
Last Update Posted Date September 13, 2021
Actual Study Start Date  ICMJE May 24, 2017
Actual Primary Completion Date July 28, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 6, 2021)
  • Dose Limiting Toxicities (DLTs) during the first 6 weeks of therapy [ Time Frame: 42 days ]
    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
  • Overall response rate (ORR) per local investigator assessment for groups A, B and C [ Time Frame: From baseline up to approximately 28 months ]
    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
Original Primary Outcome Measures  ICMJE
 (submitted: February 22, 2017)
  • Dose Limiting Toxicities (DLTs) during the first 6 weeks of therapy [ Time Frame: 42 days ]
  • Overall response rate (ORR) [ Time Frame: every 6 weeks for up to 28 months ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 6, 2021)
  • Overall Response Rate (ORR) per local investigator assessment for group E [ Time Frame: Up to approximately 28 months ]
    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
  • Progression Free Survival (PFS) per Investigator [ 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 ]
    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
  • Disease Control Rate (DCR) per Investigator [ Time Frame: Up to approximately 28 months ]
    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.
  • Duration of Response (DOR) per Investigator [ 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 ]
    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 to Response (TTR) per Investigator [ Time Frame: From start of treatment to the date of the first documented reponse (CR or PR), assessed up to approximately 28 months ]
    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
  • Overall survival (OS) [ Time Frame: from date of start of treatment to date of death due to any cause (assessed up to approximately 3.5 years) ]
    OS is defined as the time from date of start of treatment to date of death due to any cause.
  • Trough plasma Concentration (Ctrough) of PDR001 [ 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 ]
    Blood samples will be collected at indicated time points for pharmacokinetic analysis.
  • Trough plasma Concentration (Ctrough) of chemotherapy [ Time Frame: Pre-infusion on Day 1 of Cycle 1, 3 and 4 of induction phase; Cycle = 21 Days ]
    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
  • Trough plasma Concentration (Ctrough) of canakinumab [ Time Frame: Pre-infusion on Day 1 of Cycle 1, 3 and 4 of induction phase; Cycle = 21 Days ]
    Blood samples will be collected at indicated time points for pharmacokinetic analysis.
  • PDR001 Antidrug antibodies (ADA) prevalence at baseline [ Time Frame: Baseline ]
    Blood samples will be collected at indicated time points for immunogenicity analysis.
  • Canakinumab ADA prevalence at baseline [ Time Frame: Baseline ]
    Blood samples will be collected at indicated time points for immunogenicity analysis.
  • PDR001 ADA incidence during treatment [ 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 ]
    Blood samples will be collected at indicated time points for immunogenicity analysis.
  • Canakinumab ADA incidence during treatment [ 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 ]
    Blood samples will be collected at indicated time points for immunogenicity analysis.
  • Incidence of Adverse Events (AEs) [ Time Frame: through study completion, up to approximately 3.5 years ]
    Incidence of AEs (CTCAE v4.03)
Original Secondary Outcome Measures  ICMJE
 (submitted: February 22, 2017)
  • Progression Free Survival (PFS) per Investigator [ Time Frame: every 6 weeks for up to 28 months ]
  • Disease Control Rate (DCR) per Investigator [ Time Frame: every 6 weeks for up to 28 months ]
  • Duration of Response (DOR) per Investigator [ Time Frame: every 6 weeks for up to 28 months ]
  • Time to Response (TTR) per Investigator [ Time Frame: every 6 weeks for up to 28 months ]
  • Overall survival (OS) [ Time Frame: from date of start of treatment to date of death due to any cause (up to 28 months) ]
  • Peak Serum Concentration (Cmax) (PDR001) [ Time Frame: Day 1 of Cycle 1 and 4 of induction phase cycle = 21 days ]
  • Peak Plasma Concentration (Cmax) (chemotherapy) [ Time Frame: Day 1 of Cycle 1, 3 and 4; cycle = 21 days ]
  • Antidrug antibodies (ADA) prevalence at baseline [ Time Frame: Baseline ]
  • ADA incidence on treatment [ Time Frame: Throughout study until 150 day safety follow-up ]
  • Trough Serum Concentration (Cmin) (PDR001) [ Time Frame: Day 1 of Cycle 1 to 4 of induction phase; Day 1 of Cycle 1 to 4, 6, 8 and every 6 cycle afterwards of maintenance phase; cycle = 21 days ]
  • Trough PlasmaConcentration (Cmin) (chemotherapy) [ Time Frame: Day 1 of Cycle 1, 3 and 4; Cycle = 21 days ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE PDR001 in Combination With Platinum-doublet Chemotherapy and Other Immunology Agents in PD-L1 Unselected, Metastatic NSCLC Patients
Official Title  ICMJE Phase Ib, Multicenter, Open Label Study of PDR001 in Combination With Platinum Doublet Chemotherapy and Other Immunooncology Agents in PD-L1 Unselected, Metastatic NSCLS Patients (ElevatION:NSCLC-101 Trial)
Brief Summary 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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Non-small Cell Lung Cancer
Intervention  ICMJE
  • Drug: PDR001
    Powder for solution for infusion
  • Drug: Cisplatin
    Intravenous infusion
  • Drug: Gemcitabine
    Intravenous infusion
  • Drug: Pemetrexed
    Intravenous infusion
  • Drug: Carboplatin
    Intravenous infusion
  • Drug: Paclitaxel
    Intravenous infusion
  • Drug: Canakinumab
    Subcutaneous injection
Study Arms  ICMJE
  • Experimental: Group A: squamous, gem/cis+PDR001
    Interventions:
    • Drug: PDR001
    • Drug: Cisplatin
    • Drug: Gemcitabine
  • Experimental: Group B: non-squamous, pem/cis+PDR001
    Interventions:
    • Drug: PDR001
    • Drug: Cisplatin
    • Drug: Pemetrexed
  • Experimental: Group C: paclitaxel/carbo+PDR001
    Interventions:
    • Drug: PDR001
    • Drug: Carboplatin
    • Drug: Paclitaxel
  • Experimental: Group E: non-squamous, pem/cis (or carbo)+PDR001+canakinumab
    Interventions:
    • Drug: PDR001
    • Drug: Cisplatin
    • Drug: Pemetrexed
    • Drug: Carboplatin
    • Drug: Canakinumab
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: September 10, 2021)
116
Original Estimated Enrollment  ICMJE
 (submitted: February 22, 2017)
170
Actual Study Completion Date  ICMJE August 11, 2021
Actual Primary Completion Date July 28, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Main Inclusion Criteria:

  1. Patient has stage IIIB (and is not a candidate for definitive multimodality therapy) or has stage IV NSCLC or relapsed locally advanced or metastatic NSCLC as follows:

    1. Group A, group B and group C only: Patients not previously treated with any systemic anti-cancer therapy (e.g. cytotoxic drugs, targeted therapy, monoclonal antibody therapy including immunotherapy (e.g. PD-1/PD-L1 inhibitors) or targeted therapies, either experimental or not), with exception of neo-adjuvant or adjuvant therapy as depicted in inclusion criterion 4.
    2. Group D only: Patients who have received only one prior systemic therapy treatment consisting of a PD-1 and/or PD-L1 inhibitor with or without a CTLA4 inhibitor for NSCLC, with exception of neo-adjuvant or adjuvant therapy as depicted in inclusion criterion 4. The last dose of prior immunotherapy must have been administered at least 6 weeks prior to the start of study treatment (cycle 1 day 1).
  2. Histologically or cytologically confirmed diagnosis of NSCLC that is EGFR Wild-type, ALK-negative rearrangement and ROS1-negative rearrangement
  3. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
  4. Patients with at least 1 measurable tumor lesion as assessed by Computed Tomography (CT) Scan or Magnetic Resonance Imaging (MRI) according to RECIST 1.1.

Main Exclusion Criteria:

  1. Patient with a history of severe hypersensitivity reaction to the planned study treatment including gemcitabine, paclitaxel, cisplatin, carboplatin, pemetrexed or any known excipients of these drugs
  2. History of severe hypersensitivity reactions to other monoclonal antibodies, which in the opinion of the investigator may pose an increased risk of serious infusion reaction.
  3. Patient has history of interstitial lung disease or interstitial pneumonitis, including clinically significant radiation pneumonitis (i.e., affecting activities of daily living or requiring therapeutic intervention).
  4. History of leptomeningeal metastases
  5. Active, known or suspected autoimmune disease or a documented history of autoimmune disease, including ulcerative colitis and Crohn's disease (Patients with vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll).
  6. Use of any live vaccines against infectious diseases within 4 weeks of initiation of study treatment
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Belgium,   Canada,   Czechia,   France,   Germany,   Hong Kong,   Italy,   Korea, Republic of,   Netherlands,   Singapore,   Spain,   United States
Removed Location Countries Japan
 
Administrative Information
NCT Number  ICMJE NCT03064854
Other Study ID Numbers  ICMJE CPDR001C2101
2016-002815-17 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Novartis ( Novartis Pharmaceuticals )
Study Sponsor  ICMJE Novartis Pharmaceuticals
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
PRS Account Novartis
Verification Date September 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP