Clinical Trials /

Study to Assess Safety and Efficacy of Atezolizumab (MPDL3280A) Compared to Best Supportive Care Following Chemotherapy in Patients With Lung Cancer [IMpower010]

NCT02486718

Description:

This is a Phase III, global, multicenter, open-label, randomized study to compare the efficacy and safety of 16 cycles (1 cycle duration=21 days) of atezolizumab (MPDL3280A) treatment compared with best supportive care (BSC) in participants with Stage IB-Stage IIIA non-small cell lung cancer (NSCLC) following resection and adjuvant chemotherapy, as measured by disease-free survival (DFS) as assessed by the investigator and overall survival (OS). Participants, after completing up to 4 cycles of adjuvant cisplatin-based chemotherapy, will be randomized in a 1:1 ratio to receive atezolizumab for 16 cycles or BSC.

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

Active, not recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: Study to Assess Safety and Efficacy of Atezolizumab (MPDL3280A) Compared to Best Supportive Care Following Chemotherapy in Patients With Lung Cancer [IMpower010]
  • Official Title: A Phase III, Open-Label, Randomized Study to Investigate the Efficacy and Safety of Atezolizumab (Anti-PD-L1 Antibody) Compared With Best Supportive Care Following Adjuvant Cisplatin-Based Chemotherapy in Patients With Completely Resected Stage IB-IIIA Non-Small Cell Lung Cancer

Clinical Trial IDs

  • ORG STUDY ID: GO29527
  • SECONDARY ID: 2014-003205-15
  • NCT ID: NCT02486718

Conditions

  • Non-Small Cell Lung Cancer

Interventions

DrugSynonymsArms
AtezolizumabMPDL3280A; TECENTRIQAtezolizumab
CisplatinAtezolizumab
VinorelbineAtezolizumab
DocetaxelAtezolizumab
GemcitabineAtezolizumab
PemetrexedAtezolizumab

Purpose

This is a Phase III, global, multicenter, open-label, randomized study to compare the efficacy and safety of 16 cycles (1 cycle duration=21 days) of atezolizumab (MPDL3280A) treatment compared with best supportive care (BSC) in participants with Stage IB-Stage IIIA non-small cell lung cancer (NSCLC) following resection and adjuvant chemotherapy, as measured by disease-free survival (DFS) as assessed by the investigator and overall survival (OS). Participants, after completing up to 4 cycles of adjuvant cisplatin-based chemotherapy, will be randomized in a 1:1 ratio to receive atezolizumab for 16 cycles or BSC.

Trial Arms

NameTypeDescriptionInterventions
AtezolizumabExperimentalEnrollment Phase: Participants will receive four 21-day cycles of cisplatin-based chemotherapy (cisplatin plus either vinorelbine or docetaxel or gemcitabine or pemetrexed [non-squamous cell NSCLC only]), unless unacceptable toxicity, disease relapse, or participant's decision to discontinue occur. Randomization Phase: Participants will receive atezolizumab 1200 milligrams (mg) intravenously (IV) every 3 weeks (Q3W) for sixteen 21-day cycles and will undergo periodic chest X-ray and CT scan.
  • Atezolizumab
  • Cisplatin
  • Vinorelbine
  • Docetaxel
  • Gemcitabine
  • Pemetrexed
Best Supportive CareActive ComparatorEnrollment Phase: Participants will receive four 21-day cycles of cisplatin-based chemotherapy (cisplatin plus either vinorelbine or docetaxel or gemcitabine or pemetrexed [non-squamous cell NSCLC only]), unless unacceptable toxicity, disease relapse, or participant's decision to discontinue occur. Randomization Phase: After enrollment phase participants will receive only the best supportive care and will undergo periodic chest X-ray and CT scan.
  • Cisplatin
  • Vinorelbine
  • Docetaxel
  • Gemcitabine
  • Pemetrexed

Eligibility Criteria

        Inclusion Criteria:

        Inclusion Criteria for Enrollment Phase

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

          -  Histological or cytological diagnosis of Stage IB (tumors greater than or equal to
             [>/=] 4 centimeters [cm])-IIIA (T2-3 N0, T1-3 N1, T1-3 N2, T4 N0-1) NSCLC (per the
             Union Internationale Contre le Cancer staging system (UICC)/American Joint Committee
             on Cancer staging system (AJCC) staging system, 7th edition; Detterbeck et al. 2009)

          -  Participants must have had complete resection of NSCLC 4-12 weeks (>/=28 days and less
             than or equal to [</=] 84 days) prior to enrollment and must be adequately recovered
             from surgery

          -  If mediastinoscopy was not performed preoperatively, it is required that, at a
             minimum, mediastinal lymph node systematic sampling will have occurred. Systematic
             sampling is defined as removal of at least one representative lymph node at specified
             levels. MLND entails resection of all lymph nodes at those same levels. For a right
             thoracotomy, sampling or MLND is required at levels 4 and 7 and for a left
             thoracotomy, levels 5 and/or 6 and 7. Exceptions will be granted if there is clear
             documentation in the operative report or in a separately submitted addendum by the
             surgeon of exploration of the required lymph node areas, the participant will be
             considered eligible if no lymph nodes are found in those areas; if participants have
             documented N2 disease in one level (per the UICC/AJCC staging system, 7th edition;
             Detterbeck et al. 2009), not all levels need to be sampled; if the preoperative
             staging imaging results (contrast computed tomography [CT] and positron emission
             tomography [PET] scans) do not suggest evidence of disease in the mediastinum, the
             participant will be considered eligible if N2 nodal sampling is not performed per
             surgeon's decision

          -  Eligible to receive a cisplatin-based chemotherapy regimen

          -  Adequate hematologic and end-organ function

          -  Women who are not postmenopausal (>/=12 months of non-therapy-induced amenorrhea) or
             surgically sterile must have a negative serum pregnancy test result within 14 days
             prior to initiation of cisplatin-based chemotherapy

        Inclusion Criteria for Randomized Phase - Women who are not postmenopausal (>/=12 months of
        non-therapy-induced amenorrhea) or surgically sterile must have a negative serum pregnancy
        test result within 14 days prior to initiation of atezolizumab or BSC

        Exclusion Criteria:

        Exclusion Criteria for Enrollment Phase

          -  Illness or condition that may interfere with a participant's capacity to understand,
             follow, and/or comply with study procedures

          -  Pregnant and lactating women

          -  Treatment with prior systemic chemotherapy: Chemotherapy for early stage of malignancy
             with curative intent, provided that the last dose received was more than 5 years prior
             to enrollment and low-dose chemotherapy for non-malignant conditions may be allowed
             upon approval by the Medical Monitor

          -  Hormonal cancer therapy or radiation therapy as prior cancer treatment within 5 years
             before enrollment

          -  Treatment with any other investigational agent with therapeutic intent within 28 days
             prior to enrollment

          -  Participants with hearing impairment

          -  Known sensitivity to any component of the chemotherapy regimen the participant will be
             assigned to, or to mannitol

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

          -  Malignancies other than NSCLC within 5 years prior to randomization, with the
             exception of those with a negligible risk of metastasis or death (e.g., expected
             5-year OS greater than [>] 90 percent [%]) treated with expected curative outcome
             (such as adequately treated carcinoma in situ of the cervix, basal or squamous cell
             skin cancer, localized prostate cancer treated surgically with curative intent, ductal
             carcinoma in situ treated surgically with curative intent)

          -  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

          -  History of autoimmune disease, including but not limited to myasthenia gravis,
             myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis,
             inflammatory bowel disease, vascular thrombosis associated with antiphospholipid
             syndrome, Wegener's granulomatosis, Sjögren's syndrome, Guillain-Barré syndrome,
             multiple sclerosis, vasculitis, or glomerulonephritis

          -  Positive test for human immunodeficiency virus (HIV)

          -  Participants with active hepatitis B (chronic or acute; defined as having a positive
             hepatitis B surface antigen [HBsAg] test at screening) or hepatitis C

          -  Active tuberculosis

          -  Significant cardiovascular disease, such as New York Heart Association cardiac disease
             (Class II or greater), myocardial infarction, or cerebrovascular accident within the
             previous 3 months, unstable arrhythmias, or unstable angina

          -  History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis
             obliterans), drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active
             pneumonitis on screening chest CT scan

          -  Prior allogeneic bone marrow transplantation or solid organ transplant

          -  Any other diseases, metabolic dysfunction, physical examination finding, or clinical
             laboratory finding giving reasonable suspicion of a disease or condition that
             contraindicates the use of an investigational drug or that may affect the
             interpretation of the results or render the participant at high risk from treatment
             complications

          -  Known tumor PD-L1 expression status as determined by an immunohistochemistry (IHC)
             assay 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)

        Specific Exclusions for Pemetrexed Treatment

        - Participants with squamous cell histology

        Exclusion Criteria for Randomized Phase

          -  Signs or symptoms of infection within 14 days prior to randomization (severe infection
             within 28 days prior to randomization), including but not limited to hospitalization
             for complications of infection, bacteremia, or severe pneumonia

          -  Received therapeutic oral or intravenous (IV) antibiotics within 14 days prior to
             randomization

          -  Major surgical procedure within 28 days prior to randomization or anticipation of need
             for a major surgical procedure during the course of the study

          -  Administration of a live, attenuated vaccine within 4 weeks prior to initiation of
             study treatment or anticipation that such a live attenuated vaccine will be required
             during the study

          -  Treatment with systemic immunostimulatory agents (including but not limited to
             interferons or interleukin-2) within 4 weeks or 5 half-lives of the drug, whichever is
             longer, prior to randomization: Prior treatment with cancer vaccines is allowed

          -  Treatment with systemic corticosteroids or other immunosuppressive medications
             (including but not limited to prednisone, dexamethasone, cyclophosphamide,
             azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor [anti-TNF]
             agents) within 14 days prior to randomization
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Disease-Free Survival (DFS), Assessed Using Computed Tomography (CT)/Magnetic Resonance Imaging (MRI)/X-Ray
Time Frame:From randomization to the date of first recurrence of NSCLC, occurrence of new primary NSCLC, or death from any cause, whichever occurs first (up to approximately 131 months)
Safety Issue:
Description:DFS will be assessed by the investigator in PD-L1 subpopulation within the Stage II-IIIA population, in all randomized patients with Stage II-IIIA NSCLC, and in the ITT population.

Secondary Outcome Measures

Measure:Overall Survival (OS) in the ITT Population
Time Frame:Baseline up to death from any cause (up to approximately 131 months)
Safety Issue:
Description:
Measure:Percentage of Participants Who are Disease-Free at Year 3, Assessed Using CT/MRI/X-Ray
Time Frame:Year 3
Safety Issue:
Description:DFS rates will be measured in the PD-L1 subpopulation within the Stage II-IIIA population, in all randomized patients with Stage II-IIIA NSCLC, and in the ITT population.
Measure:Percentage of Participants Who are Disease-Free at Year 5, Assessed Using CT/MRI/X-Ray
Time Frame:Year 5
Safety Issue:
Description:DFS rates will be measured in the PD-L1 subpopulation within the Stage II-IIIA population, in all randomized patients with Stage II-IIIA NSCLC, and in the ITT population.
Measure:DFS Within Selected Populations
Time Frame:From randomization to the date of first recurrence of NSCLC, occurrence of new primary NSCLC, or death from any cause, whichever occurs first (up to approximately 67 months)
Safety Issue:
Description:DFS rates will be measured within the PD-L1 subpopulation in patients with Stage II-IIIA NSCLC.
Measure:Percentage of Participants with Adverse Events
Time Frame:Baseline up to approximately 131 months
Safety Issue:
Description:
Measure:Percentage of Participants With Anti-Therapeutic Antibodies (ATAs) to Atezolizumab
Time Frame:Predose (Hour 0) on Day (D) 1 of Cycles (Cy) 1, 2, 3, 4, 8, 16 (Cy length=21 days), at treatment discontinuation (TD) (up to 12 months), 120 days after last atezolizumab administration (up to 16 months)
Safety Issue:
Description:
Measure:Maximum Plasma Concentration (Cmax) of Atezolizumab
Time Frame:Post-infusion on Day 1 of Cycle 1 (cy length = 21 days)
Safety Issue:
Description:
Measure:Minimum Serum Concentration (Cmin) at Steady-State Within a Dosing Interval of Atezolizumab
Time Frame:Prior to infusion on D1 of Cy2, 3, 4, 8, 16 (Cy length = 21 days), and at study termination (up to approximately 131 months)
Safety Issue:
Description:

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Active, not recruiting
Lead Sponsor:Hoffmann-La Roche

Last Updated

June 10, 2021