CHIO3: CHemotherapy combined with immune checkpoint inhibitor for operable stage IIIA/B (N2) Non-Small cell lung...

Despite a deluge of perioperative non-small cell lung cancer (NSCLC) checkpoint inhibitor trials, none have looked exclusively at an N2+ population. This trial focused on operable N2+ NSCLC and uniquely sought to evaluate N2 nodal clearance (N2NC) rates after treatment with chemotherapy and durvalumab.

We conducted a single arm multi-institutional phase 2 trial. Eligible subjects had surgically resectable stage III NSCLC with pathologically proven N2 disease, performance status 0-1. N3 disease and EGFR mutation were exclusionary. Participants received 4 cycles of platinum doublet + durvalumab followed by lobectomy or greater, and adjuvant durvalumab Q4 weeks for one year. The primary endpoint (PEP) was N2NC (ypN0-1); the objective was an increase of N2NC to ≥ 50% from a historical rate of 30% with platinum doublet chemotherapy. Secondary endpoints were resection rates, safety, feasibility, overall survival (OS) and event-free survival (EFS) at 18 months. Planned accrual was 55 patients, anticipating 42 patients undergoing resection.

Between 2021 and 2023, 37 patients were enrolled and 30 patients (81%) underwent resection. The study was closed early because the PEP was exceeded on interim analysis. N2NC was 73.3% (22/30); pathologic complete response (pCR) 30% (9/30); R0 resection 93.3% (28/30). At median follow up of 16.3 months, EFS at 18 months was 60.6% (95% CI 44-83%) overall, and 73.4% (95% CI 56-97%) for the resected cohort (n = 30). 16% (6/37) had grade 3 and higher treatment-related adverse events, most commonly lymphopenia.

In this surgically challenging, documented N2 + NSCLC population, neoadjuvant durvalumab plus chemotherapy was feasible with low toxicity, high rates of mediastinal nodal clearance, and complete resection. Glossary of Abbreviations.