NCT05500092

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

• Status: Active Not Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 17 (actual)
• Sponsor: Montefiore Medical Center · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

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

Detailed description

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.

Conditions

• Resectable Stage IIA to IIIB Non-small Cell Lung Cancer

Interventions

Type	Name	Description
DRUG	Nivolumab	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
RADIATION	(8gy x 3)	sub-ablative stereotactic radiation therapy (8 Gy x 3) directed at the primary lung tumor
DRUG	Platinum Doublet	Standard of care doublet platinum therapy

Timeline

• Start date: 2023-01-25
• Primary completion: 2025-07-01
• Completion: 2030-05-01
• First posted: 2022-08-12
• Last updated: 2026-01-28

Locations

4 sites across 1 country: United States

Regulatory

• FDA-regulated drug study