Clinical Trials /

A Study of Atezolizumab Compared With a Single-Agent Chemotherapy in Treatment Naïve Participants With Locally Advanced or Recurrent or Metastatic Non-Small Cell Lung Cancer Who Are Deemed Unsuitable For Platinum-Doublet Chemotherapy

NCT03191786

Description:

This Phase III, global, multicenter, open-label, randomized, controlled study will evaluate the efficacy and safety of atezolizumab (an anti-programmed death-ligand 1 [anti-PD-L1] antibody) compared with a single agent chemotherapy regimen by investigator choice (vinorelbine or gemcitabine) in treatment-naïve participants with locally advanced or metastatic non-small cell lung cancer (NSCLC) who are deemed unsuitable for any platinum-doublet chemotherapy due to poor performance status (Eastern Cooperative Oncology Group [ECOG] performance status of 2-3).

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

Active, not recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: A Study of Atezolizumab Compared With Chemotherapy in Treatment Naïve Participants With Locally Advanced or Recurrent or Metastatic Non-Small Cell Lung Cancer Who Are Deemed Unsuitable For Platinum-Containing Therapy
  • Official Title: A Phase III, Open-Label, Multicenter, Randomized Study to Investigate the Efficacy and Safety of Atezolizumab Compared With Chemotherapy in Patients With Treatment Naïve Advanced or Recurrent (Stage IIIb Not Amenable for Multimodality Treatment) or Metastatic (Stage IV) Non-Small Cell Lung Cancer Who Are Deemed Unsuitable for Platinum-Containing Therapy

Clinical Trial IDs

  • ORG STUDY ID: MO29872
  • SECONDARY ID: 2015-004105-16
  • NCT ID: NCT03191786

Conditions

  • Non-Small Cell Lung Cancer

Interventions

DrugSynonymsArms
Atezolizumab (MPDL3280A), an engineered anti-PD-L1 antibodyMPDL3280AAtezolizumab
VinorelbineNavelbine®Single Agent Chemotherapy (Vinorelbine or Gemcitabine)
GemcitabineGemzar®Single Agent Chemotherapy (Vinorelbine or Gemcitabine)

Purpose

This Phase III, global, multicenter, open-label, randomized, controlled study will evaluate the efficacy and safety of atezolizumab (an anti-programmed death-ligand 1 [anti-PD-L1] antibody) compared with a single agent chemotherapy regimen by investigator choice (vinorelbine or gemcitabine) in treatment-naïve participants with locally advanced or metastatic non-small cell lung cancer (NSCLC) who are deemed unsuitable for any platinum-doublet chemotherapy due to poor performance status (Eastern Cooperative Oncology Group [ECOG] performance status of 2-3).

Trial Arms

NameTypeDescriptionInterventions
AtezolizumabExperimentalParticipants will receive atezolizumab 1200 milligrams (mg) intravenous (IV) infusion on Day 1 of each 21-day cycle until loss of clinical benefit, unacceptable toxicity, participant or physician decision to discontinue, or death.
  • Atezolizumab (MPDL3280A), an engineered anti-PD-L1 antibody
Single Agent Chemotherapy (Vinorelbine or Gemcitabine)Active ComparatorParticipants will receive single agent chemotherapy; either vinorelbine oral or IV, or gemcitabine IV, according to the label based on investigator's choice.
  • Vinorelbine
  • Gemcitabine

Eligibility Criteria

        Inclusion Criteria:

          -  Histologically or cytologically confirmed diagnosis of advanced or recurrent (Stage
             IIIB not amenable for multimodality treatment) or metastatic (Stage IV) NSCLC as per
             the American Joint Committee on Cancer (AJCC) 7th edition

          -  No sensitizing epidermal growth factor receptor (EGFR) mutation (L858R or exon 19
             deletions) or anaplastic lymphoma kinase (ALK) fusion oncogene detected

          -  No prior systemic treatment for advanced or recurrent (Stage IIIB not amenable for
             multimodality treatment) or metastatic (Stage IV) NSCLC as per the AJCC 7th edition

          -  Life expectancy greater than or equal to (>/=) 8 weeks

          -  Deemed unsuitable by the investigator for any platinum-doublet chemotherapy due to
             poor performance status (ECOG performance status of 2-3). However, participants >= 70
             years of age who have an ECOG PS of 0 or 1 may be included due to: a) substantial
             comorbidities; b) contraindication(s) for any platinum-doublet chemotherapy

          -  Representative formalin-fixed paraffin-embedded (FPPE) tumor tissue block obtained
             during course of disease (archival tissue) or at screening

          -  Participants with treated, asymptomatic central nervous system (CNS) metastases are
             eligible, provided they meet all of the following criteria: Measurable disease outside
             CNS; Only supratentorial and cerebellar metastases allowed; No ongoing requirement for
             corticosteroids as therapy for CNS disease; No stereotactic radiation within 7 days or
             whole-brain radiation within 14 days prior to randomization; No evidence of interim
             progression between the completion of CNS-directed therapy and the screening
             radiographic study

          -  Adequate hematologic and end organ function

          -  Female participants of childbearing potential randomized to the atezolizumab treatment
             arm agree to use protocol defined methods of contraception

        Exclusion Criteria:

        Cancer-Specific Exclusion Criteria:

          -  Participants younger than 70 years who have an ECOG performance status of 0 or 1

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

          -  Uncontrolled tumor-related pain

          -  Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent
             drainage procedures (once monthly or more frequently)

          -  Uncontrolled or symptomatic hyerpcalcemia (ionized calcium > 1.5 mmol/L or calcium >12
             mg/dL or corrected serum calcium >ULN)

          -  History of other malignancy within 5 years prior to screening, with the exception of
             those with a negligible risk of metastasis or death treated with expected curative
             outcome

          -  National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE)
             version 4.0 (v4.0) Grade 3 or higher toxicities due to any prior therapy (example
             [e.g.], radiotherapy) (excluding alopecia), which have not shown improvement and are
             strictly considered to interfere with current study medication

          -  Participants who have received prior neo-adjuvant, adjuvant chemotherapy,
             radiotherapy, 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, radiotherapy, or chemoradiotherapy

        General Medical Exclusion Criteria:

          -  History of autoimmune disease except autoimmune-related hypothyroidism and controlled
             Type I diabetes mellitus

          -  History of idiopathic pulmonary fibrosis (IPF), organizing pneumonia (e.g.,
             bronchiolitis obliterans), drug-induced pneumonitis, idiopathic pneumonitis, or
             evidence of active pneumonitis

          -  Known positivity for human immunodeficiency virus (HIV)

          -  Known active hepatitis B or hepatitis C

          -  Active tuberculosis

          -  Severe infections within 4 weeks prior to randomization

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

          -  Major surgical procedure other than for diagnosis within 4 weeks prior to
             randomization or anticipation of need for a major surgical procedure during the course
             of the study

          -  Prior allogeneic bone marrow transplantation or solid organ transplant

          -  Participants with an illness or condition that may interfere with capacity or
             compliance with the study protocol, as per investigator's judgment

          -  Treatment with any other investigational agent or participation in another clinical
             study with therapeutic intent within 28 days prior to randomization

        Exclusion Criteria Related to Atezolizumab:

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

          -  Known hypersensitivity to biopharmaceuticals produced in Chinese hamster ovary cells
             or any component of the atezolizumab formulation

          -  Oral or IV antibiotic treatment

          -  Administration of a live, attenuated vaccine within 4 weeks before randomization or
             anticipation that such a live attenuated vaccine will be required during the study

          -  Prior treatment with cluster of differentiation 137 (CD137) agonists or immune
             checkpoint blockade therapies, anti-programmed death-1 (anti-PD-1), and anti-PD-L1
             therapeutic antibodies

          -  Treatment with systemic immunostimulatory agents within 4 weeks or 5 half-lives of the
             drug, whichever is shorter, prior to randomization

          -  Treatment with systemic corticosteroids or other immunosuppressive medications

          -  Participants not willing to stop treatment with traditional herbal medicines

        Exclusion Criteria Related to Chemotherapy:

          -  Known sensitivity and contraindications to the 2 comparative chemotherapy agents (that
             is [i.e.] vinorelbine, oral or intravenous, and gemcitabine, intravenous)
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Overall Survival
Time Frame:From randomization up to death from any cause (up to approximately 3.5 years)
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Percentage of Participants Who Are Alive at Specified Timepoints
Time Frame:6, 12, 18 and 24 months
Safety Issue:
Description:
Measure:Percentage of Participants With Objective Response, as Determined by the Investigator Using Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1 (v1.1)
Time Frame:From randomization to the first occurence of disease progression or death from any cause, whichever occurs first (up to approximately 3.5 years)
Safety Issue:
Description:Objective response is defined as partial response (PR) plus complete response (CR).
Measure:Progression-Free Survival (PFS), as Determined by the Investigator Using RECIST v1.1
Time Frame:From randomization to the first occurence of disease progression or death from any cause, whichever occurs first (up to approximately 3.5 years)
Safety Issue:
Description:
Measure:Duration of Response, as Determined by the Investigator Using RECIST v1.1
Time Frame:Time from the first occurrence of a documented objective response to the time of disease progression or death from any cause, whichever occurs first (up to approximately 3.5 years)
Safety Issue:
Description:
Measure:Percentage of Participants With Adverse Events (AEs)
Time Frame:From randomization up to approximately 3.5 years
Safety Issue:
Description:
Measure:Change From Baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - Core 30 (EORTC-QLQ-C30) Score
Time Frame:Baseline, Day 1 of each treatment cycle up to 30 days after last dose (up to approximately 3.5 years) (Cycle length = 21 days)
Safety Issue:
Description:
Measure:Change From Baseline in EORTC QLQ Supplementary Lung Cancer Module 13 (EORTC QLQ-LC13) Score
Time Frame:Baseline, Day 1 of each treatment cycle up to 30 days after last dose (up to approximately 3.5 years) (Cycle length = 21 days)
Safety Issue:
Description:
Measure:Time to Deterioration in Patient-Reported Lung Cancer Symptoms as Assessed by EORTC QLQ-C30 Score
Time Frame:From baseline up to approximately 3.5 years
Safety Issue:
Description:
Measure:Time to Deterioration in Patient-Reported Lung Cancer Symptoms As Assessed by EORTC QLQ-LC13 Score
Time Frame:From baseline up to approximately 3.5 years
Safety Issue:
Description:

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Hoffmann-La Roche

Last Updated