Neoadjuvant Toripalimab plus chemotherapy in patients with stage IIB-IIIB NSCLC: A single-center, prospective, single-arm, phase 2 trial (Renaissance Study).

Abstract

e21128 Background: Neoadjuvant treatment of a programmed cell death protein 1 (PD-1) inhibitor plus chemotherapy has been shown to be promising in treating resectable non-small cell lung cancer (NSCLC). The current study aimed to investigate the efficacy and safety of toripalimab plus double platinum-based chemotherapy as neoadjuvant treatment for stage IIB-IIIB NSCLC. Methods: Study eligibility involved stage IIB-IIIB, wildtype EGFR/ALK NSCLC pts with ECOG PS 0-1 status. Pts received 2-4 cycles of toripalimab (240mg, q3w) plus cisplatin-based chemotherapy. All pts were assessed by imaging/surgical indication after the second cycle of treatment. Pts who cannot undergo surgery will be reassessed after another 1-2 cycles of neoadjuvant therapy. Primary endpoints were major pathological response (MPR), complete pathological response (pCR). Secondary endpoints were objective response rate (ORR), R0 resection rate and safety. Results: A total of 52 eligible pts (median age: 62, IQR: 45-76; female: 4, 7.7%) were enrolled and received 2-4 cycles neoadjuvant treatment since Mar 2021. 42 pts had squamous cell carcinoma and 10 pts had non-squamous cell carcinoma. Disease distribution in stage IIB, IIIA and IIIB consisted of 14, 30 and 8 pts, respectively. 15 pts were undergoing preoperative treatment or preparing for surgery, 32 pts underwent resection (median interval between neoadjuvant treatment and surgery: 67 days, IQR 39-113), 5 pts were unsuitable for surgery (1 pt had immune-related pneumonia; 2 pts who had stable disease were considered radical radiotherapy and immunotherapy for maintenance due to the difficulty of surgery induced by tumor location and lymph node metastasis; 2 pts continued toripalimab plus chemotherapy or radiotherapy due to high surgical risk induced by old age and poor performance status). 20 pts (20/32, 62.5%) achieved MPR, including 16 pts (16/32, 50%) with pCR. 6 pts (6/8, 75%), 12 pts (12/18, 66.7%), and 2 pts (2/6, 33.3%) with stage IIB, IIIA and IIIB achieved MPR respectively. R0 resection was achieved for all 32 pts (100%). 23 pts underwent surgery with cN2/N1 at baseline (23/24, 95.8%) achieved nodal downstaging. For pts who finished radiological reassessment (45 pts finished the treatment schedule and only 43 pts finished radiological reassessment), ORR was 83.7% (36/43). Grade 1-2 TRAEs were reported in 33 patients (33/45, 73.3%). Grade 3-4 TRAEs were reported in 6 pts (6/45, 13.3%). Conclusions: Toripalimab plus platinum-based doublet as neoadjuvant treatment yields a high MPR rate, manageable toxicity and feasible surgical resection in stage IIB-IIIB NSCLC. Clinical trial information: NCT04606303.