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

Phase 3

Active, not recruiting

Conditions: Non-Small Cell Lung Cancer

Interventions: Drug: Atezolizumab
Drug: Cisplatin
Drug: Vinorelbine
Drug: Docetaxel
Drug: Gemcitabine
Drug: Pemetrexed

Registration Number: NCT02486718

Lead Sponsor: Hoffmann-La Roche

Brief Summary: 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.

Detailed Description: Not available

Recruitment & Eligibility

Status: ACTIVE_NOT_RECRUITING

Sex: All

Target Recruitment: 1280

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Atezolizumab	Atezolizumab	Enrollment 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	Enrollment 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	Docetaxel	Enrollment 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	Pemetrexed	Enrollment 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	Gemcitabine	Enrollment 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.
Best Supportive Care	Vinorelbine	Enrollment 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.
Best Supportive Care	Docetaxel	Enrollment 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.
Best Supportive Care	Pemetrexed	Enrollment 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.
Atezolizumab	Vinorelbine	Enrollment 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.
Best Supportive Care	Cisplatin	Enrollment 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.
Best Supportive Care	Gemcitabine	Enrollment 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.

Primary Outcome Measures

Name	Time	Method
DFS in All Randomized Stage II-IIIA Population	Up to 95 months	DFS was defined as the time from randomization to the first recurrence of NSCLC or occurrence of new primary NSCLC as determined by the investigator or death, whichever occurs first. DFS was analyzed in participants with disease stage II-IIIA. Kaplan-Meier methodology was used to estimate the median DFS for each treatment arm.
Disease-Free Survival (DFS) in Intent-to-treat (ITT) Population	Up to 95 months	DFS was defined as the time from randomization to the first recurrence of NSCLC or occurrence of new primary NSCLC as determined by the investigator or death, whichever occurs first. Kaplan-Meier methodology was used to estimate the median DFS for each treatment arm.
DFS in the Programmed Death-ligand 1 (PD-L1) SP263 ≥ 1% Tumor Cell (TC) Subpopulation Within the Stage II-IIIA Population	Up to 95 months	DFS was defined as the time from randomization to the first recurrence of NSCLC or occurrence of new primary NSCLC as determined by the investigator or death, whichever occurs first. DFS was analyzed in PD-L1 ≥1% subpopulation within the Stage II-IIIA population. Kaplan-Meier methodology was used to estimate the median DFS for each treatment arm.

Secondary Outcome Measures

Name	Time	Method
Disease-free Rate at Year 5 in All Randomized Stage II-IIIA Population	Year 5	DFS rate was defined as percentage of participants who were disease-free at Year 5. DFS rate was analyzed in participants with disease stage II-IIIA. The DFS rate was estimated by the Kaplan-Meier methodology for each treatment arm. Percentages have been rounded off to the nearest decimal.
Overall Survival (OS) in the ITT Population	Up to 20 years	OS was defined as the time from randomization to death from any cause.
Disease-free Rate at Year 3 in ITT Population	Year 3	DFS rate was defined as percentage of participants who were disease-free at Year 3. The DFS rate was estimated by the Kaplan-Meier methodology for each treatment arm. Percentages have been rounded off to the nearest decimal.
Disease-free Rate at Year 3 in All Randomized Stage II-IIIA Population	Year 3	DFS rate was defined as percentage of participants who were disease-free at Year 3. DFS rate was analyzed in participants with disease stage II-IIIA. The DFS rate was estimated by the Kaplan-Meier methodology for each treatment arm. Percentages have been rounded off to the nearest decimal.
Disease-free Rate at Year 3 in PD-L1 (SP263 ≥ 1% TC) Subpopulation Within the Stage II-IIIA Population	Year 3	DFS rate was defined as percentage of participants who were disease-free at Year 3. DFS rate was analyzed in PD-L1 subpopulation within the Stage II-IIIA population. The DFS rate was estimated by the Kaplan-Meier methodology for each treatment arm. Percentages have been rounded off to the nearest decimal.
Disease-free Rate at Year 5 in ITT Population	Year 5	DFS rate was defined as percentage of participants who were disease-free at Year 5. The DFS rate was estimated by the Kaplan-Meier methodology for each treatment arm. Percentages have been rounded off to the nearest decimal.
Disease-free Rate at Year 5 in PD-L1 (SP263 ≥ 1% TC) Subpopulation Within the Stage II-IIIA Population	Year 5	DFS rate was defined as percentage of participants who were disease-free at Year 5. DFS rate was analyzed in PD-L1 subpopulation within the Stage II-IIIA population. The DFS rate was estimated by the Kaplan-Meier methodology for each treatment arm. Percentages have been rounded off to the nearest decimal.
DFS in the PD-L1 (SP263 ≥ 50% TC) Subpopulation Within the Stage II-IIIA Population	Up to 95 months	DFS was defined as the time from randomization to the first recurrence of NSCLC or occurrence of new primary NSCLC as determined by the investigator or death, whichever occurs first. DFS was analyzed in PD-L1 subpopulation within the Stage II-IIIA population. Kaplan-Meier methodology was used to estimate the median DFS for each treatment arm.
Percentage of Participants With Adverse Events (AEs)	Up to 20 years	An AE is any untoward medical occurrence in a participant when administered a pharmaceutical product regardless of the causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom/disease temporally associated with the use of an investigational product, whether or not considered related to the investigational product.
Percentage of Participants With Anti-Therapeutic Antibodies (ATAs) to Atezolizumab	Predose (Hour 0) on Day 1 of Cycles 2, 3, 4, 8, 16 (Cycle length = 21 days), at treatment discontinuation (TD) (up to 12 months), 120 days after last atezolizumab administration (up to 16 months)	The percentage of ATA (Also called anti-drug antibodies (ADA))-positive participants after drug administration were determined for participants exposed to atezolizumab. For determining post-baseline incidence, participants were considered to be ADA-positive if they were ADA-negative or had missing data at baseline but developed an ADA response following study drug exposure, or if they were ADA-positive at baseline and the titer of 1 or more post-baseline samples was at least 0.60 titer units (t.u.) greater than the baseline titer result.
Maximum Plasma Concentration (Cmax) of Atezolizumab	30 min post-infusion on Day 1 of Cycle 1 (Cycle length = 21 days)
Minimum Serum Concentration (Cmin) at Steady-State Within a Dosing Interval of Atezolizumab	Prior to infusion on Day 1 of Cycles 1, 2, 3, 4, 8, 16 (Cycle length = 21 days), at study discontinuation visit (up to 12 months), Day 120 post last dose of atezolizumab (up to 16 months)

Trial Locations

Locations (152): Kaiser Permanente
🇺🇸
Vallejo, California, United States
Eastern Connecticut Hematology and Oncology Associates
🇺🇸
Norwich, Connecticut, United States
SCRI Florida Cancer Specialists North
🇺🇸
Saint Petersburg, Florida, United States
Valley Hospital
🇺🇸
Paramus, New Jersey, United States
Overlook Medical Center
🇺🇸
Summit, New Jersey, United States
Centre Regional de Lutte contre le Cancer Val d Aurelle - Paul Lamarque
🇫🇷
Montpellier, France
Centre Hospitalier Regional Sud Reunion
🇫🇷
Saint Pierre, France
Centre Hospitalier de Saint-Quentin
🇫🇷
Saint-Quentin, France
Ev.Krankenhaus Bielefeld gGmbH
🇩🇪
Bielefeld, Germany
LungenClinic Grosshansdorf GmbH
🇩🇪
Großhansdorf, Germany
Scroll for more (142 remaining)
Kaiser Permanente
🇺🇸Vallejo, California, United States