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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 : Recruiting
First Posted : February 27, 2017
Last Update Posted : March 1, 2019
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 March 1, 2019
Actual Study Start Date  ICMJE May 24, 2017
Estimated Primary Completion Date December 10, 2021   (Final data collection date for primary outcome measure)
Current 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 ]
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03064854 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: October 23, 2018)
  • 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 ]
  • Progression Free Survival (PDF) by blinded independend review commitee (BIRC) [ Time Frame: every 6 weeks for up to 28 months ]
  • Overall response rate (ORR) by blinded independend review commitee (BIRC) [ Time Frame: every 6 weeks for up to 28 months ]
  • Disease control rate (DCR) by blinded independend review commitee (BIRC) [ Time Frame: every 6 weeks for up to 28 months ]
  • Duration of Response (DOR) by blinded independend review commitee (BIRC) [ Time Frame: every 6 weeks for up to 28 months ]
  • Time to Response (TTR) by blinded independend review commitee (BIRC) [ Time Frame: every 6 weeks for up to 28 months ]
  • Incidence of AEs (CTCAE v4.03) [ Time Frame: through study completion, an average of one year ]
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: 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 Recruiting
Estimated Enrollment  ICMJE
 (submitted: February 28, 2019)
160
Original Estimated Enrollment  ICMJE
 (submitted: February 22, 2017)
170
Estimated Study Completion Date  ICMJE December 10, 2021
Estimated Primary Completion Date December 10, 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: Novartis Pharmaceuticals 1-888-669-6682 novartis.email@novartis.com
Contact: Novartis Pharmaceuticals +41613241111 novartis.email@novartis.com
Listed Location Countries  ICMJE Belgium,   Canada,   Czechia,   France,   Germany,   Hong Kong,   Italy,   Japan,   Korea, Republic of,   Netherlands,   Singapore,   Spain,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03064854
Other Study ID Numbers  ICMJE CPDR001C2101
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 February 2019

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