Clinical Trials /

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

NCT03064854

Description:

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.

Related Conditions:
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: PDR001 in Combination With Platinum-doublet Chemotherapy in PD-L1 Unselected, Metastatic NSCLC Patients (ElevatION:NSCLC-101 Trial)
  • Official Title: Phase Ib, Multicenter, Open Label Study of PDR001 in Combination With Platinum-doublet Chemotherapy in PD-L1 Unselected, Metastatic NSCLC Patients (ElevatION:NSCLC-101 Trial)

Clinical Trial IDs

  • ORG STUDY ID: CPDR001C2101
  • NCT ID: NCT03064854

Conditions

  • Non-small Cell Lung Cancer

Interventions

DrugSynonymsArms
PDR001Group A: squamous, gem/cis+PDR001
CisplatinGroup A: squamous, gem/cis+PDR001
GemcitabineGroup A: squamous, gem/cis+PDR001
PemetrexedGroup B: non-squamous, pem/cis+PDR001
CarboplatinGroup C: paclitaxel/carbo+PDR001
PaclitaxelGroup C: paclitaxel/carbo+PDR001

Purpose

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 in treatment naive patients with PD-L1 unselected, advanced NSCLC, and to estimate the preliminary anti-tumor activity of PDR001 in combination with platinum-doublet chemotherapy in this patient population.

Trial Arms

NameTypeDescriptionInterventions
Group A: squamous, gem/cis+PDR001Experimental
  • PDR001
  • Cisplatin
  • Gemcitabine
Group B: non-squamous, pem/cis+PDR001Experimental
  • PDR001
  • Cisplatin
  • Pemetrexed
Group C: paclitaxel/carbo+PDR001Experimental
  • PDR001
  • Carboplatin
  • Paclitaxel
Group D non-squamous, ARM 1 or ARM 2Experimental
  • PDR001
  • Cisplatin
  • Pemetrexed
  • Carboplatin

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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Dose Limiting Toxicities (DLTs) during the first 6 weeks of therapy
Time Frame:42 days
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Progression Free Survival (PFS) per Investigator
Time Frame:every 6 weeks for up to 28 months
Safety Issue:
Description:
Measure:Disease Control Rate (DCR) per Investigator
Time Frame:every 6 weeks for up to 28 months
Safety Issue:
Description:
Measure:Duration of Response (DOR) per Investigator
Time Frame:every 6 weeks for up to 28 months
Safety Issue:
Description:
Measure:Time to Response (TTR) per Investigator
Time Frame:every 6 weeks for up to 28 months
Safety Issue:
Description:
Measure:Overall survival (OS)
Time Frame:from date of start of treatment to date of death due to any cause (up to 28 months)
Safety Issue:
Description:
Measure:Peak Serum Concentration (Cmax) (PDR001)
Time Frame:Day 1 of Cycle 1 and 4 of induction phase cycle = 21 days
Safety Issue:
Description:
Measure:Peak Plasma Concentration (Cmax) (chemotherapy)
Time Frame:Day 1 of Cycle 1, 3 and 4; cycle = 21 days
Safety Issue:
Description:
Measure:Antidrug antibodies (ADA) prevalence at baseline
Time Frame:Baseline
Safety Issue:
Description:
Measure:ADA incidence on treatment
Time Frame:Throughout study until 150 day safety follow-up
Safety Issue:
Description:
Measure: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
Safety Issue:
Description:
Measure:Trough PlasmaConcentration (Cmin) (chemotherapy)
Time Frame:Day 1 of Cycle 1, 3 and 4; Cycle = 21 days
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Novartis Pharmaceuticals

Trial Keywords

  • PDR001
  • immunotherapy
  • Non-small cell lung cancer
  • lung
  • NSCLC

Last Updated

August 23, 2017