Induction therapy with PD-1 antibody combined with platinum-based doublet chemotherapy for locally-advanced non-small cell lung cancer: A randomised controlled, open-label, phase 2 trial.

8044 Background: Chemoradiotherpay plus immunotherapy is recommended for unresectable locally-advanced non-small cell lung cancer (NSCLC) based on PACIFIC trial. However, it is unclear whether surgery can provide survival benefit for patients with tumors initially unresectable transformed into resectable ones after chemoimmunotherapy. This trial aims to investigate the efficacy and safety of the therapeutic regimen of chemoimmunotherapy plus surgery or radiotherapy. Methods: Patients with unresectable stage IIIB-IIIC NSCLC were enrolled to receive 4 cycles (q21d) of PD-1 antibody (Serplulimab, 4.5mg/kg) and platinum-based doublet chemotherapy. After the induction therapy, those with disease downstaged to IIIA or lower stage and resectable were randomized to receive radical surgery or radiotherapy with a ratio of 1:1, and those with stage IIIB or higher stage or unresectable disease after induction therapy were then treated by oncologists. Primary endpoint was event-free survival (EFS). Secondary endpoints included objective response rate (ORR), major pathologic response (MPR), pathologic complete response (pCR), progression-free survival (PFS), disease-free survival (DFS), overall survival (OS), R0 rate of resection, severe adverse event (SAE) rate, and health related quality of life (HRQol). Preliminary short-term results were collected. Results: One hundred patients will be enrolled as planned, and a total of 82 patients were enrolled by the data cutoff date (January 6, 2024). Fifty-four and 28 patients were diagnosed with stage IIIB and IIIC disease, respectively. The percentage of squamous carcinomas, adenocarcinomas, and NSCLCs not otherwise specified were 68.3% (56/82), 15.9% (13/82), and 15.9% (13/82), respectively. ORR in 73 evaluable patients was 74.0% (54/73). Twenty-six of them are still in induction therapy phase, and the other 47 and 9 patients received 4 cycles and 1-3 cycles of induction therapy, respectively. Thirty-one patients had downstaged and resectable disease after 4 cycles of induction therapy, and 26 of them were randomized to arm A (n = 13) and arm B (n = 13), and 5 refused randomization (3 received surgery). One patient received surgery after 2 cycles of induction therapy. In 56 patients finished 1-4 cycles of induction therapy, the rate of conversion to resectability was 57.1% (32/56). In total, 17 patients received surgery, and the MPR and pCR rate in 16 evaluable patients were 62.5% (10/16) and 31.3% (5/16), respectively. The grade 3-5 adverse event rate in 56 patients finished induction therapy was 50.0% (28/56). One patient died of immune-related pneumonia. Conclusions: Induction therapy with PD-1 antibody (Serplulimab) and chemotherapy could transform half of unresectable stage IIIB-IIIC NSCLC into resectable, and the efficacy and safety were satisfactory. Clinical trial information: NCT05766800 .