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

August 11, 2022 updated by: Novartis Pharmaceuticals

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

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
111

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

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

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

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

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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
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
From baseline up to approximately 28 months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
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
Up to approximately 28 months
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
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
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.
Up to approximately 28 months
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
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
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
From start of treatment to the date of the first documented reponse (CR or PR), assessed up to approximately 28 months
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.
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
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.
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
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
Pre-infusion on Day 1 of Cycle 1, 3 and 4 of induction phase; Cycle = 21 Days
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.
Pre-infusion on Day 1 of Cycle 1, 3 and 4 of induction phase; Cycle = 21 Days
PDR001 Antidrug antibodies (ADA) prevalence at baseline
Time Frame: Baseline
Blood samples will be collected at indicated time points for immunogenicity analysis.
Baseline
Canakinumab ADA prevalence at baseline
Time Frame: Baseline
Blood samples will be collected at indicated time points for immunogenicity analysis.
Baseline
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.
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
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.
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)
Time Frame: through study completion, up to approximately 3.5 years
Incidence of AEs (CTCAE v4.03)
through study completion, up to approximately 3.5 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Novartis Pharmaceuticals

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
May 24, 2017

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
July 28, 2021

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
July 28, 2021

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
February 6, 2017

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 22, 2017

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
February 27, 2017

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
August 15, 2022

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 11, 2022

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
August 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant 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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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