An open label, randomized study of neoadjuvant nivolumab and chemotherapy, with or without sub-ablative stereotactic body radiation therapy, for resectable stage IIA to IIIB non-small cell lung cancer
Primary Objective * To compare the complete pathological response rate after 3 cycles of neoadjuvant nivolumab and platinum-based doublet chemotherapy vs. the same regimen with the addition of sub-ablative stereotactic radiation therapy (8 Gy x 3) directed at the primary lung tumor. Secondary Objectives * To characterize the rate of Major Pathological Response (MPR), defined as ≤ 10% residual viable tumor cells at the time of surgical resection in the primary tumor and lymph nodes, as assessed by local pathology laboratory. * To characterize rates of Event Free Survival (EFS), defined as survival without documented disease progression per RECIST v1.1 that precludes surgery for local or distant disease recurrence. Exploratory Objectives * To characterize the rate of pathological downstaging of biopsy confirmed positive lymph nodes not in the stereotactic body radiation therapy (SBRT) field. * To characterize rates of Disease-Free Survival (DFS), defined as survival without local or distant recurrence or occurrence of new primary NSCLC. * To characterize rates of Overall Survival (OS) after study enrollment. * To characterize the incidence of adverse events, graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. * To describe surgical safety and the incidence and severity of surgery-related adverse events. * To characterize rates of clearance of circulating tumor DNA (ctDNA) following neoadjuvant therapy and definitive surgical treatment * To evaluate whole tumor RNA-sequencing (RNAseq) from pre- and post- treatment tissue samples to assess for predictors and signatures of pathologic response. * To evaluate of gene expression in pre- and post-treatment blood samples to assess for predictors and signatures of complete pathologic response. * To assess the expression characteristics of PD-L1, infiltrating immune cells and tumor mutational burden (TMB), and their association with clinical outcomes.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
17
Patients randomized to the Nivolumab + Platinum Doublet Chemotherapy only arm will receive three cycles of nivolumab at a dose of 360 mg every three weeks along with a platinum-based chemotherapy doublet (cisplatin or carboplatin plus pemetrexed for adenocarcinoma, cisplatin or carboplatin plus docetaxel, paclitaxel, or gemcitabine for squamous NSCLC) with sub-ablative stereotactic radiation therapy (8 Gy x 3) directed at the primary lung tumor
sub-ablative stereotactic radiation therapy (8 Gy x 3) directed at the primary lung tumor
Standard of care doublet platinum therapy
Washington University in St. Louis
St Louis, Missouri, United States
Montefiore Medical Center-Albert Einstein College of Medicine
The Bronx, New York, United States
White Plains Hospital (WPH)
White Plains, New York, United States
Penn State Health Milton S. Hershey Medical Center
Hershey, Pennsylvania, United States
Complete Pathological Response
Complete pathological response (CPR) rate observed after neoadjuvant therapy and surgical resection. Complete pathological response will be defined as the absence of tumor cells in the resected specimen upon histopathological examination and will be reported as the number/percentage of participants who had complete pathological response. Results will be summarized for each study arm.
Time frame: After 3 cycles. Each cycle is defined as 3 weeks
Major Pathological Response
Major Pathological Response (MPR) rate will be assessed. MPR will be defined as ≤ 10% residual viable tumor cells, at the time of surgical resection, in the primary tumor and resected lymph nodes, as assessed by local pathology laboratory. MPR rate and corresponding 95% Clopper-Pearson confidence intervals will be calculated for each treatment arm.
Time frame: After 3 cycles. Each cycle is defined as 3 weeks
Event Free Survival
Event free survival (EFS) will be defined as survival without evidence of documented disease progression, per RECIST v1.1 criteria, that precludes surgery for local or distant disease recurrence. Results will be summarized by study arm.
Time frame: From the time of enrollment up to approximately 5 years
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