Principal Investigator
Enrollment Status
Clinical Trial ID
Clinical Trial 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.
Phase
Phase 3
Funding Agency/Sponsor
Industrial
Disease
Thoracic Oncology
Enrollment Eligibility
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 [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