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

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)

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 Overview

• Status: Terminated
• Conditions: Non-small Cell Lung Cancer
• Intervention / Treatment: Drug: Paclitaxel; Drug: Gemcitabine; Drug: Pemetrexed; Drug: Cisplatin; Drug: Carboplatin; Drug: PDR001; Drug: Canakinumab

• Study Type: Interventional
• Enrollment (Actual): 111
• Phase: Phase 1

Contacts and Locations

Study Locations

• Belgium
  • Leuven, Belgium, 3000
    • Novartis Investigative Site
  • Roeselare, Belgium, 8800
    • Novartis Investigative Site
• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 2M9
      • Novartis Investigative Site
• Czechia
  • Praha 4, Czechia, 140 59
    • Novartis Investigative Site
• France
  • Lyon Cedex, France, 69373
    • Novartis Investigative Site
  • Marseille Cedex 05, France, 13885
    • Novartis Investigative Site
• Germany
  • Gottingen, Germany, 37075
    • Novartis Investigative Site
  • Koeln, Germany, 51109
    • Novartis Investigative Site
• Hong Kong
  • Pokfulam, Hong Kong
    • Novartis Investigative Site
• Italy
  • FC
    • Meldola, FC, Italy, 47014
      • Novartis Investigative Site
  • MI
    • Rozzano, MI, Italy, 20089
      • Novartis Investigative Site
  • PN
    • Aviano, PN, Italy, 33081
      • Novartis Investigative Site
• Korea, Republic of
  • Seoul, Korea, Republic of, 03080
    • Novartis Investigative Site
• Netherlands
  • Amsterdam, Netherlands, 1066 CX
    • Novartis Investigative Site
• Singapore
  • Singapore, Singapore, 169610
    • Novartis Investigative Site
• Spain
  • Madrid, Spain, 28041
    • Novartis Investigative Site
  • Madrid, Spain, 28034
    • Novartis Investigative Site
  • Catalunya
    • Barcelona, Catalunya, Spain, 08035
      • Novartis Investigative Site
• United States
  • Arkansas
    • Fayetteville, Arkansas, United States, 72703
      • Highlands Oncology Group
  • California
    • Santa Monica, California, United States, 90404
      • UCLA Santa Monica Hematology / Oncology SC-2
    • Stanford, California, United States, 94305
      • Stanford Cancer Center SC
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Health System SC
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine SC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group A: squamous, gem/cis+PDR001	Drug: Gemcitabine; Intravenous infusion; Drug: Cisplatin; Intravenous infusion; Drug: PDR001; Powder for solution for infusion
Experimental: Group B: non-squamous, pem/cis+PDR001	Drug: Pemetrexed; Intravenous infusion; Drug: Cisplatin; Intravenous infusion; Drug: PDR001; Powder for solution for infusion
Experimental: Group C: paclitaxel/carbo+PDR001	Drug: Paclitaxel; Intravenous infusion; Drug: Carboplatin; Intravenous infusion; Drug: PDR001; Powder for solution for infusion
Experimental: Group E: non-squamous, pem/cis (or carbo)+PDR001+canakinumab	Drug: Pemetrexed; Intravenous infusion; Drug: Cisplatin; Intravenous infusion; Drug: Carboplatin; Intravenous infusion; Drug: PDR001; Powder for solution for infusion; Drug: Canakinumab; Subcutaneous injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	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	From baseline up to approximately 28 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	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	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.	Up to approximately 28 months
Duration of Response (DOR) per Investigator	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	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	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.	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.	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	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.	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.	Baseline
Canakinumab ADA prevalence at baseline	Blood samples will be collected at indicated time points for immunogenicity analysis.	Baseline
PDR001 ADA incidence during treatment	Blood samples will be collected at indicated time points for immunogenicity analysis.	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.	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)	through study completion, up to approximately 3.5 years

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Publications and helpful links

Helpful Links

• Results for CPDR001C2101 from the Novartis Clinical Trial Website
• A Plain Language Trial Summary is available on novctrd.com

Study record dates

Study Major Dates

• Study Start (Actual): May 24, 2017
• Primary Completion (Actual): July 28, 2021
• Study Completion (Actual): July 28, 2021

Study Registration Dates

• First Submitted: February 6, 2017
• First Submitted That Met QC Criteria: February 22, 2017
• First Posted (Actual): February 27, 2017

Study Record Updates

• Last Update Posted (Actual): August 15, 2022
• Last Update Submitted That Met QC Criteria: August 11, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Keywords: lung; immunotherapy; NSCLC; Non-small cell lung cancer; PDR001
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Immune Checkpoint Inhibitors; Folic Acid Antagonists; Gemcitabine; Carboplatin; Paclitaxel; Cisplatin; Pemetrexed; Spartalizumab
• Other Study ID Numbers: CPDR001C2101; 2016-002815-17 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No