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 LUNG CANCER RESECTION AND CHEMOTHERAPY FOR EARLY STAGE LUNG CANCER

Phase 1

Conditions: ON-SMALL CELL LUNG CANCER
MedDRA version: 21.1Level: LLTClassification code 10029514Term: Non-small cell lung cancer NOSSystem Organ Class: 100000004864
Therapeutic area: Diseases [C] - Cancer [C04]

Registration Number: EUCTR2014-003205-15-IT

Lead Sponsor: F. HOFFMANN - LA ROCHE LTD.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

Sex: All

Target Recruitment: 1127

Inclusion Criteria

Patients must meet all of the following criteria to be eligible to enter the enrollment phase and receive cisplatin-based chemotherapy regimen in this study:
•A representative formalin-fixed paraffin-embedded (FFPE) tumor specimen in paraffin block (preferred) or 15 (or more) unstained, freshly cut, serial sections (on slides) from an FFPE resected tumor specimen is required for participation in this study. This specimen must be accompanied by the associated pathology report.
•Signed Informed Consent Form
•Age ¿ 18 years
•ECOG performance status of 0 or 1
•Histological or cytological diagnosis of Stage IB (tumors ¿ 4 cm)¿IIIA (T2¿3 N0, T1¿3 N1, T1 3 N2, T4 N0 1) NSCLC (per the Union Internationale Contre le Cancer/American Joint Committee on Cancer [UICC/AJCC] staging system, 7th edition)
•Patients must have had complete resection of NSCLC 4¿12 weeks (¿ 28 days and ¿ 84 days) prior to enrollment and must be adequately recovered from surgery
Accepted types of resection include any of the following: lobectomy, sleeve lobectomy, bilobectomy, or pneumonectomy.
Resection by segmentectomy or wedge resection is not allowed.
•If mediastinoscopy was not performed preoperatively, it is expected that, at a minimum, mediastinal lymph node systematic sampling will have occurred, though complete mediastinal lymph node dissection (MLND) is preferred. 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.
For a complete List please refer to the section of Inclusion criteria in the Protocol
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 790
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 337

Exclusion Criteria

•Illness or condition that may interfere with a patient’s capacity to understand, follow, and/or comply with study procedures
•Pregnant and lactating women
•Treatment with prior systemic chemotherapy
•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
•A hearing loss (measured by audiometry) of 25 dB at two contiguous frequencies (audiometry will only be required for patients who have suspected or definitive hearing loss)
•Known sensitivity to any component of the chemotherapy regimen the patient will be assigned to, or to mannitol
•Prior treatment with CD137 agonists or immune checkpoint blockade therapies, anti¿PD 1, and anti¿PD-L1 therapeutic antibodies
•Malignancies other than NSCLC within 5 years prior to enrollment, with the exception of those with a negligible risk of metastasis or death (e.g., expected 5 year OS ¿ 90%) 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 HIV
•Patients 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 patient at high risk from treatment complications
•Known tumor PD-L1 expression status as determined by an IHC assay from other clinical studies (e.g., patients 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)

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To evaluate the efficacy of 16 cycles of atezolizumab treatment compared with best supportive care as measured by disease-free survival (DFS) as assessed by the investigator.;Secondary Objective: To evaluate the efficacy of 16 cycles of atezolizumab treatment compared with BSC as measured by OS;Timepoint(s) of evaluation of this end point: About 5 years;Primary end point(s): •DFS, defined as the time from randomization to the date of occurrence of any of the following, whichever occurs first: First recurrence of NSCLC, as determined by the investigator after an integrated assessment of radiographic data, biopsy sample results (if available), and clinical status<br>Occurrence of new primary NSCLC, as assessed by the investigator<br>Death from any cause

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): •OS, defined as the time from randomization to death from any cause;Timepoint(s) of evaluation of this end point: About 5 years

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