This phase II trial tests how well the use of circulating tumor DNA testing works to determine the length of durvalumab therapy for patients with stage III non small cell lung cancer that that cannot or is unable to be removed by surgery (inoperable or unresectable). 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). Immunotherapy with monoclonal antibodies, such as durvalumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Circulating tumor DNA (ctDNA) are tiny pieces of cancer DNA in the blood that show how well the body responds to a treatment for a disease or condition. ctDNA may predict the presence or absence of a small number of cancer cells in the body after cancer treatment. Using ctDNA tests to determine when blood is clear of cancer may help determine the optimal cycle to stop treatment with durvalumab for patients with inoperable or unresectable stage III non small cell lung cancer.
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT05757843.
PRIMARY OBJECTIVE:
I. Determine if de-escalating the number of durvalumab cycles based on personalized ctDNA clearance guidance to at least 6 cycles after chemoradiation (CRT) in stage III non-resectable non small cell lung cancer (NSCLC) has non-inferior 2-year progression free survival (PFS) rate compared with historical control of empirically treating stage III non-resectable NSCLC for 1 year of durvalumab after CRT.
SECONDARY OBJECTIVES:
I. Estimate the 24-month overall survival (OS) of patient treated with consolidation durvalumab based on personalized ctDNA clearance guidance for at least 6 cycles after CRT in stage III non-resectable NSCLC.
II. Estimate the 24-month PFS in patients with persistently detectable ctDNA without radiographic progression of disease after receiving ≥ 6 months of consolidation durvalumab.
CORRELATIVE/EXPLORATORY OBJECTIVES:
I. Describe the tumor mutational profile for phylogenetic analysis in patients who have persistently detectable ctDNA without progression compared to those who have achieved clearance of ctDNA.
II. Assess the feasibility of collecting 24-hour urine based ctDNA analysis.
OUTLINE:
Patients receive durvalumab intravenously (IV) on day 1 of each cycle. Cycles repeat every 4 weeks for up to 1 year in the absence of disease progression, unacceptable toxicity or, starting with cycle 5, the clearance of detectable ctDNA for 2 consecutive instances, approximately 4 weeks apart. Patients undergo required blood sample collection for ctDNA evaluation during screening and on study. Patients may also undergo tumor biopsy during screening and optional blood sample collection throughout the trial.
Patients are followed for up to 24 months from the start of durvalumab treatment.
Lead OrganizationIndiana University/Melvin and Bren Simon Cancer Center
Principal InvestigatorNasser H. Hanna
