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A Study of Atezolizumab in Combination With Carboplatin or Cisplatin + Pemetrexed Compared With Carboplatin or Cisplatin + Pemetrexed in Participants Who Are Chemotherapy-Naive and Have Stage IV Non-Squamous Non-Small Cell Lung Cancer (NSCLC) (IMpower 132)

NCT02657434

Description:

This is a randomized, Phase III, multicenter, open-label study designed to evaluate the safety and efficacy of atezolizumab in combination with cisplatin or carboplatin + pemetrexed compared with treatment with cisplatin or carboplatin + pemetrexed in participants who are chemotherapy-naive and have Stage IV non-squamous NSCLC. Eligible participants will be randomized by a 1:1 ratio into 2 groups: Arm A (Atezolizumab + Carboplatin or Cisplatin + Pemetrexed) and Arm B (Carboplatin or Cisplatin + Pemetrexed). The study will be conducted in two phases: Induction Phase and Maintenance Phase.

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

Active, not recruiting

Phase:

Phase 3

Trial Eligibility

Document

A Study of <span class="go-doc-concept go-doc-intervention">Atezolizumab</span> in Combination With <span class="go-doc-concept go-doc-intervention">Carboplatin</span> or <span class="go-doc-concept go-doc-intervention">Cisplatin</span> + <span class="go-doc-concept go-doc-intervention">Pemetrexed</span> Compared With <span class="go-doc-concept go-doc-intervention">Carboplatin</span> or <span class="go-doc-concept go-doc-intervention">Cisplatin</span> + <span class="go-doc-concept go-doc-intervention">Pemetrexed</span> in Participants Who Are <span class="go-doc-concept go-doc-intervention">Chemotherapy</span>-Naive and Have Stage IV Non-Squamous Non-Small Cell Lung Cancer

Title

  • Brief Title: A Study of Atezolizumab in Combination With Carboplatin or Cisplatin + Pemetrexed Compared With Carboplatin or Cisplatin + Pemetrexed in Participants Who Are Chemotherapy-Naive and Have Stage IV Non-Squamous Non-Small Cell Lung Cancer
  • Official Title: A Phase III, Open-Label, Randomized Study of Atezolizumab (MPDL3280A, Anti-Pd-L1 Antibody) in Combination With Carboplatin or Cisplatin + Pemetrexed Compared With Carboplatin or Cisplatin + Pemetrexed in Patients Who Are Chemotherapy-Naive and Have Stage IV Non-Squamous Non-Small Cell Lung Cancer
  • Clinical Trial IDs

    NCT ID: NCT02657434

    ORG ID: GO29438

    NCI ID: 2015-003605-42

    Trial Conditions

    Metastatic Non-Squamous Non-Small Cell Lung Cancer

    Trial Interventions

    Drug Synonyms Arms
    Atezolizumab MPDL3280A Arm A (Atezolizumab with Carboplatin or cisplatin+Pemetrexed)
    Carboplatin Arm A (Atezolizumab with Carboplatin or cisplatin+Pemetrexed), Arm B (Carboplatin or Cisplatin+Pemetrexed)
    Cisplatin Arm A (Atezolizumab with Carboplatin or cisplatin+Pemetrexed), Arm B (Carboplatin or Cisplatin+Pemetrexed)
    Pemetrexed Arm A (Atezolizumab with Carboplatin or cisplatin+Pemetrexed), Arm B (Carboplatin or Cisplatin+Pemetrexed)

    Trial Purpose

    This is a randomized, Phase III, multicenter, open-label study designed to evaluate the
    safety and efficacy of atezolizumab in combination with cisplatin or carboplatin +
    pemetrexed compared with treatment with cisplatin or carboplatin + pemetrexed in
    participants who are chemotherapy-naive and have Stage IV non-squamous non-small cell lung
    cancer (NSCLC).

    Detailed Description

    Trial Arms

    Name Type Description Interventions
    Arm A (Atezolizumab with Carboplatin or cisplatin+Pemetrexed) Experimental Participants will receive intravenous (IV) infusion of 1200 milligrams (mg) of atezolimumab on Day 1 every 3 weeks (q3w), IV infusion of 500 milligrams per meter square (mg/m^2) pemetrexed on Day 1 q3w, and as per investigator's choice either IV infusion of carboplatin on Day 1 q3w with a dose calculated using 'Calvert formula' to obtain area under concentration versus time (AUC) = 6 milligrams per milliliter per minute (mg/mL/min) or IV infusion of 75 mg/m^2 cisplatin q3w on Day 1 q3w, during induction dosing period of 4 or 6 cycles (1 Cycle = 3 Weeks). Participants who experience clinical benefit during the induction phase will begin maintenance therapy. Participants will receive IV infusion of 1200 mg of atezolizumab and 500 mg/m^2 of pemetrexed on Day 1 q3w until disease progression in the maintenance period. Atezolizumab, Carboplatin, Cisplatin, Pemetrexed
    Arm B (Carboplatin or Cisplatin+Pemetrexed) Active Comparator Participants will receive IV infusion of 500 mg/m^2 pemetrexed on Day 1 q3w, and as per investigator's choice of either IV infusion of carboplatin on Day 1 q3w with a dose calculated using 'Calvert formula' to obtain AUC =6 mg/mL/min or IV infusion of 75 mg/m^2 cisplatin q3w on Day 1 q3w, during induction dosing period for 4 or 6 cycles (1 Cycle = 3 Weeks). Participants who do not experience disease progression during the induction phase will begin maintenance therapy. Participants will receive IV infusion of 500 mg/m^2 of pemetrexed on Day 1 q3w until disease progression in the maintenance period. Carboplatin, Cisplatin, Pemetrexed

    Eligibility Criteria

    Inclusion Criteria:

    - Male or female, 18 years of age or older

    - Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

    - Histologically or cytologically confirmed, Stage IV non-squamous NSCLC

    - No prior treatment for Stage IV non-squamous NSCLC. Participants with a sensitizing
    mutation in the epidermal growth factor receptor (EGFR) gene or with an anaplastic
    lymphoma kinase (ALK) fusion oncogene are excluded.

    - Participants who have received prior neo-adjuvant, adjuvant chemotherapy, or
    chemoradiotherapy with curative intent for non-metastatic disease must have
    experienced a treatment-free interval of at least 6 months from randomization since
    the last chemotherapy or completion of chemoradiotherapy

    - Known programmed death-ligand 1 (PD-L1) tumor status as determined by an
    immunohistochemistry (IHC) assay performed by a central laboratory on previously
    obtained archival tumor tissue or tissue obtained from a biopsy at screening

    - Measurable disease, as defined by Response Evaluation Criteria in Solid Tumors
    Version 1.1 (RECIST v1.1)

    - Adequate hematologic and end organ function

    - For women of childbearing potential: agreement to remain abstinent or use
    contraceptive methods that result in a failure rate of less than (<) 1 percent (%)
    per year during the treatment period and for at least 90 days after the last dose of
    study treatment

    - For men: agreement to remain abstinent or use contraceptive measures and agreement to
    refrain from donating sperm

    Exclusion Criteria:

    Cancer-Specific Exclusions

    - Active or untreated central nervous system (CNS) metastases as determined by computed
    tomography (CT) or magnetic resonance imaging (MRI) evaluation during screening and
    prior radiographic assessments

    - Spinal cord compression not definitively treated with surgery and/or radiation or
    previously diagnosed and treated spinal cord compression without evidence that
    disease has been clinically stable for >= 2 weeks prior to randomization

    - Leptomeningeal disease

    - Uncontrolled tumor-related pain

    - Uncontrolled or symptomatic hypercalcemia (greater than [>] 1.5 millimole/Liter
    ionized calcium or calcium > 12 milligram/deciliter or corrected serum calcium >upper
    limit of normal)

    - Malignancies other than NSCLC within 5 years prior to randomization

    - Known tumor PD-L1 expression status from other clinical studies (e.g., participants
    whose PD-L1 expression status was determined during screening for entry into a study
    with anti-PD-1 or anti-PD L1 antibodies but were not eligible are excluded)

    General Medical Exclusions:

    - History of severe allergic, anaphylactic, or other hypersensitivity reactions to
    chimeric or humanized antibodies or fusion proteins

    - History of certain autoimmune disease

    - History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced
    pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis

    - Severe infections within 4 weeks prior to randomization

    - Significant cardiovascular disease, such as New York Heart Association cardiac
    disease (Class II or greater), myocardial infarction within 3 months prior to
    randomization, unstable arrhythmias, or unstable angina

    Exclusion Criteria Related to Medications and Chemotherapy:

    - Any approved anti-cancer therapy, including chemotherapy, or hormonal therapy within
    3 weeks prior to initiation of study treatment

    - Prior treatment with CD137 agonists or immune checkpoint blockade therapies,
    anti-PD-1, and anti-PD-L1 therapeutic antibodies

    - Treatment with systemic immunostimulatory agents within 4 weeks prior to
    randomization

    - Treatment with systemic immunosuppressive medications

    Exclusion Criteria Related to Chemotherapy:

    - History of allergic reactions to cisplatin, carboplatin, or other platinum-containing
    compounds

    - Participants with hearing impairment (cisplatin)

    - Grade >= 2 peripheral neuropathy as defined by National Cancer Institute Common
    Terminology Criteria for Adverse Events (NCI CTCAE) version 4.0 criteria (cisplatin)

    - Creatinine clearance (CRCL) =< 60 milliliter (mL)/minute (min) for cisplatin or < 45
    mL/min for carboplatin

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    Progression Free Survival Time as Assessed by the Investigator Using Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST V1.1)

    Secondary Outcome Measures

    Overall Survival Time

    Percentage of Participants with an Objective Response (Complete Response [CR] or Partial Response [PR]) Assessed by the Investigator Using RECIST V1.1

    Duration of Response as Determined by the Investigator Using RECIST v1.1

    Time to Response as Determined by the Investigator According to RECIST v1.1

    Progression Free Survival Time as Determined by the Independent Review Facility Using RECIST V1.1

    Percentage of Participants Who Were Alive after One and Two Years\n

    Time to Deterioration in Patient-Reported Lung Cancer Symptoms Using European Organization for the Research and Treatment of Cancer (EORTC) Quality-of-Life Questionnaire-Core 30 (QLQ-C30) and Lung Cancer Module (EORTC QLQ-LC13) Symptom Subscales

    Time to Deterioration in Patient-Reported Lung Cancer Symptoms Using the Symptoms in Lung Cancer (SILC) Scale Symptom Score\n

    Maximum Observed Serum Atezolizumab Concentration (Cmax) After Infusion (Arm A)

    Minimum Observed Serum Atezolizumab Concentration (Cmin) Prior to Infusion (Arm A)\n

    Plasma Concentrations for Carboplatin or Cisplatin (Arm A) Cmax

    Plasma Concentrations for Pemetrexed (Arm A)

    Trial Keywords