A Multi-Institutional Randomized Phase III Trial of Neoadjuvant Chemoimmunotherapy Followed By Surgery Versus Upfront...

The standard treatment for resectable non-small cell lung cancer (NSCLC) has traditionally been upfront surgery, followed by adjuvant therapy according to pathological stage. Although recent trials have demonstrated the superiority of surgery after neoadjuvant chemoimmunotherapy over chemotherapy alone, studies directly comparing it with upfront surgery remain lacking. This trial aims to determine the optimal perioperative treatment strategy for resectable NSCLC.

This is a multicenter, randomized, phase III trial designed to assess the superiority of neoadjuvant chemoimmunotherapy over upfront surgery followed by adjuvant therapy in terms of overall survival in patients with resectable clinical stage II-III NSCLC. Patients are randomized in a 1:1 ratio to receive either (1) upfront surgery followed by cisplatin-based chemotherapy (every 3 weeks for 4 cycles) and immune checkpoint inhibitor monotherapy (up to 1 year for patients with PD-L1 TPS≥1%) or (2) neoadjuvant nivolumab plus platinum-based chemotherapy (every 3 weeks for 3 cycles) followed by surgery. The primary endpoint is the overall survival. Secondary endpoints include progression-free survival, time to distant metastasis, objective response rate to neoadjuvant therapy, and adverse events. A total of 330 patients will be enrolled over 5 years. The trial was initiated in March 2025 and registered in the Japan Registry of Clinical Trials (study number: jRCTs031240747).

As immunotherapy has become an integral component of NSCLC management in the perioperative setting, this trial is expected to provide critical evidence to refine optimal perioperative treatment strategies for patients with resectable stage II-III NSCLC.