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

• ClinicalTrials.gov Identifier: NCT03064854
• Recruitment Status: Terminated
• First Posted: February 27, 2017
• Last Update Posted: August 15, 2022
• Sponsor: Novartis Pharmaceuticals
• Information provided by (Responsible Party): Novartis ( Novartis Pharmaceuticals )

Tracking Information

• First Submitted Date: February 6, 2017
• First Posted Date: February 27, 2017
• Last Update Posted Date: August 15, 2022
• Actual Study Start Date: May 24, 2017
• Actual Primary Completion Date: July 28, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (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 (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 ]

Current Secondary Outcome Measures (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 (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: PDR001 in Combination With Platinum-doublet Chemotherapy and Other Immunology Agents in PD-L1 Unselected, Metastatic NSCLC Patients
• Official Title: 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: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Non-Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Non-small Cell Lung Cancer

Intervention

• 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

• 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

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: July 25, 2022): 111
• Original Estimated Enrollment (submitted: February 22, 2017): 170
• Actual Study Completion Date: July 28, 2021
• Actual Primary Completion Date: July 28, 2021 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Belgium, Canada, Czechia, France, Germany, Hong Kong, Italy, Korea, Republic of, Netherlands, Singapore, Spain, United States
• Removed Location Countries: Japan

Administrative Information

• NCT Number: NCT03064854
• Other Study ID Numbers: 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

• Plan to Share IPD: No

• Current Responsible Party: Novartis ( Novartis Pharmaceuticals )
• Original Responsible Party: Same as current
• Current Study Sponsor: Novartis Pharmaceuticals
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Novartis Pharmaceuticals; Novartis Pharmaceuticals

• PRS Account: Novartis
• Verification Date: August 2022