In this study circulating tumor DNA (ctDNA) blood testing is used to detect the residual blood cancer. If residual cancer using this blood test is detected there may be at higher risk of having the cancer return. The study is going to test whether or not the number of circulating cancer cells detected in the blood can be reduced by administration durvalumab after the standard treatment if you are tested positive for the residual cancer.
Pathologically (histologically or cytologically proven) NSCLC. Tumors with any component of small cell lung cancer are not allowed.
AJCC 8th edition clinical or pathological stage IA2 to IIIC or locoregionally recurrent disease. Stage IA1 tumors are excluded unless recurrent with radiographic solid component -or- pathologic invasive component of > 10 mm.
Received curative intent therapy with surgery and/or radiation. Note: May have received chemotherapy.
Completed all intended therapy (surgery, radiation, and/or chemotherapy) - AND- no more than 32 weeks has elapsed after the last day of this therapy.
Involvement in the planning and/or conduct of the study
History of Grade 3 or higher pneumonitis from prior radiation; patients with grade 2 radiation pneumonitis may be considered for enrollment with permission from the Protocol Director or Co-Director.
History of another primary malignancy and currently undergoing active treatment Exception: May participate if receiving adjuvant endocrine therapy for breast or prostate cancer.
Expected to require ongoing chronic treatment with systemic immunosuppressive medication after enrollment.
Parallel
AVENIO ctDNA Surveillance Kit
DeviceRoche Sequencing and Life Science kit to detect minimal residue disease (MRD)
Durvalumab
DrugParticipants in the intervention arm will receive Durvalumab (1500 mg IV every 4 weeks for up to 12 months) as monotherapy or 20mg/kg if weight is 30kg or less.
Durvalumab (Imfinzi) alone or in combination with platinum-based chemotherapy
DrugParticipants in the intervention arm (Cohort 1 MRD+) will receive a fixed dose of Durvalumab (1500 mg IV every 4 weeks for up to 12 months), either as monotherapy or in combination with a platinum-based chemotherapy regimen (investigator's choice). Platinum-based chemotherapy options include carboplatin, cisplatin, pemetrexed, paclitaxel, or nab-paclitaxel, administered per standard of care for up to 4 cycles.
Decrease in ctDNA Level
Change in minimal residual disease (MRD) will be assessed on the basis of reduction of circulating tumor DNA (ctDNA) in the blood of participants in Cohort 1 MRD+ only. ctDNA is an indicator of MRD. The outcome will be reported as the number of participants who have a ≥ 3-fold drop in ctDNA levels after 2 cycles of durvalumab treatment, a number without dispersion.
Presence or absence of detectable ctDNA
Circulating tumor DNA (ctDNA) in the blood is an indicator of minimal residual disease (MRD), a risk factor for future relapse or progression. The outcome will be reported as the number of Cohort 1 MRD+ participants for whom, following 2 cycles of durvalumab, ctDNA was detected, not detected, or unable to be determined, each a number without dispersion. Available data for Cohort 2 MRD- participants will also be reported for the 8-week timepoint.
Overall survival (OS)
Overall survival (OS) defined as the duration from study registration until death due to any cause. The outcome will be reported as the number of participants in each cohort known to be alive at 12 months after study registration, a number without dispersion.
Disease-free survival (DFS)
Disease-free survival (DFS) is defined as the number of participants remaining alive without disease progression (DP), symptomatic deterioration, or death due to any cause. DP is assessed according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria, as follows. * Complete Response (CR) = Disappearance of all target lesions * Partial Response (PR) = ≥ 30% decrease in the sum of the longest diameter of target lesions * Progressive disease (PD) = 20% increase in the sum of the diameters of target lesions (must be \> 5 mm), unequivocal progression of non-target lesions, and/or the appearance of one or more new lesion(s) * Stable disease (SD) = Small changes that do not meet any of the above criteria The outcome will be reported as the number of participants who meet the criteria for DFS, a number without dispersion.
Related Adverse Events
Related adverse events (AEs) are deleterious events determined to be possibly, probably, or definitely-related to durvalumab treatment. The outcome will be reported as the number of related AEs experienced by the participants in Cohort 1 MRD+ only (ie, durvalumab treatment cohort), a number without dispersion.
Click on the lead sponsor to view all of their trials.
Stanford University
Lead sponsor
AstraZeneca
Collaborator
