This phase III trial compares the effect of adding AZD6738 to durvalumab versus durvalumab alone to increase time without cancer in patients with non-small cell lung cancer, following treatment with chemotherapy and surgery. AZD6738 may stop the growth of tumor cells and may kill them by blocking some of the enzymes needed for cell growth. Durvalumab is a monoclonal antibody that may interfere with the ability of tumor cells to grow and spread. A monoclonal antibody is a type of protein that can bind to certain targets in the body, such as molecules that cause the body to make an immune response (antigens). Adding AZD6738 to durvalumab may increase time without cancer in patients with non-small cell lung cancer, following treatment with chemotherapy and surgery.
PRIMARY OBJECTIVE: I. To assess for improvement in disease free survival (DFS) in patients who do not achieve pathologic complete response (pCR) following neoadjuvant therapy and patients who receive adjuvant combination immunotherapy with durvalumab and AZD6738 (ceralasertib) compared to those who receive monotherapy with durvalumab. SECONDARY OBJECTIVE: I. To evaluate any difference in overall survival (OS) with patients who receive durvalumab and AZD6738 (ceralasertib) compared to those who receive monotherapy with durvalumab. EXPLORATORY OBJECTIVES: I. To evaluate any difference in disease free survival (DFS) with patients who receive durvalumab and AZD6738 (ceralasertib) compared to those who receive monotherapy with durvalumab according to PD-L1, stage, prior immune checkpoint inhibitor (ICI) type, and histology. II. To evaluate any difference in overall survival (OS) with patients who receive durvalumab and AZD6738 (ceralasertib) compared to those who receive monotherapy with durvalumab according to PD-L1, stage, prior ICI type, and histology. CORRELATIVE OBJECTIVE: I. To perform correlative analyses on tissue and blood biospecimens collected within this trial. OUTLINE: Patients are randomized to 1 of 2 arms. ARM A: Starting 4-12 weeks after surgery, patients receive durvalumab intravenously (IV) over 60 minutes on day 1 of each cycle. Cycles repeat every 28 days for 12 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo computed tomography (CT) scan and blood sample collection throughout the study and may undergo echocardiography as clinically indicated. ARM B: Starting 4-12 weeks after surgery, patients receive AZD6738 orally (PO) twice daily (BID) on days 1-7 and durvalumab IV over 60 minutes on day 8 of each cycle. Cycles repeat every 28 days for 12 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo CT scan and blood sample collection throughout the study and may undergo echocardiography as clinically indicated. After completion of study treatment, patients are followed up every 12 weeks for 2 years then every 24 weeks until year 5 then every 12 months until 10 years from randomization.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
630
Undergo blood sample collection
Given PO
Undergo CT scan
Given IV
Undergo echocardiography
NEA Baptist Memorial Hospital and Fowler Family Cancer Center - Jonesboro
Jonesboro, Arkansas, United States
Tower Cancer Research Foundation
Beverly Hills, California, United States
Cedars Sinai Medical Center
Los Angeles, California, United States
Cedars-Sinai Cancer - Tarzana
Tarzana, California, United States
Torrance Memorial Physician Network - Cancer Care
Torrance, California, United States
Disease free survival (DFS)
Will estimate DFS distributions using the Kaplan-Meier method and employ Cox proportional hazards models to estimate the treatment hazard ratios. The comparison of DFS will use a logrank test stratified on the randomization stratification factors with a one-sided type I error rate of 2.5%. Other comparisons of groups will be made using the logrank test and Cox modeling. Point estimates will be accompanied by the corresponding two-sided 95% confidence intervals.
Time frame: From randomization to the earliest event defined as the first recurrence of non-small cell lung cancer (NSCLC), any new lung cancer or death, up to 10 years
Overall survival (OS)
Will estimate OS distributions using the Kaplan-Meier method and employ Cox proportional hazards models to estimate the treatment hazard ratios. The comparison of OS will use a logrank test stratified on the randomization stratification factors with a one-sided type I error rate of 2.5%. Other comparisons of groups will be made using the logrank test and Cox modeling. Point estimates will be accompanied by the corresponding two-sided 95% confidence intervals.
Time frame: From randomization to death from any cause, up to 10 years
Incidence of adverse events
Toxicity will be assessed by summaries by Common Terminology Criteria for Adverse Event grade.
Time frame: Up to 10 years
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Hartford Hospital
Hartford, Connecticut, United States
Midstate Medical Center
Meriden, Connecticut, United States
The Hospital of Central Connecticut
New Britain, Connecticut, United States
Beebe South Coastal Health Campus
Millville, Delaware, United States
Helen F Graham Cancer Center
Newark, Delaware, United States
...and 183 more locations