Biomarkers of nivolumab benefit in resectable non-small cell lung cancer

Perioperative nivolumab significantly improved event-free survival (EFS) compared with placebo in patients with resectable non-small cell lung cancer (NSCLC) in the CheckMate 77T study (ClinicalTrials.gov NCT04025879 )1. Here, after randomization, 98 out of 229 patients who received nivolumab and 92 out of 232 patients who received placebo had evaluable biomarkers (41% of randomized patients). Of the 98 patients receiving nivolumab, 83 (85%) had detectable circulating tumour DNA (ctDNA) before initiating neoadjuvant treatment and 90 (92%) at neoadjuvant treatment completion. Of the 92 placebo-treated patients, 75 (82%) had detectable ctDNA at the treatment start and 78 (85%) at completion. Among the 98 nivolumab-treated patients, 76 (78%) had detectable and evaluable ctDNA before and after neoadjuvant treatment, and 50 of them (66%) had pre-surgical ctDNA clearance, and 25 out of 50 (50%) had pathologic complete response (pCR). For the placebo-treated group, these values were 64 out 92 (70%) for detectable and evaluable ctDNA before and after neoadjuvant treatment, and 24 out of 64 (38%) had pre-surgical ctDNA clearance, and 3 out of 24 (12%) had pCR. Furthermore, 4 out of 48 (8%) patients in the nivolumab group and 9 out of 44 (20%) in the placebo group who were negative for molecular residual disease (MRD) after surgery and before adjuvant treatment initiation became positive during the adjuvant treatment period; all had disease recurrence. EFS seemed to be prolonged with nivolumab (n = 60) versus placebo (n = 45) in patients with single or co-alterations in any of the KEAP1, STK11, CDKN2A and/or SMARCA4 driver genes (hazard ratio, 0.48; 95% confidence interval, 0.28–0.83). In a machine-learning model trained using biomarker-evaluable patients, top predictors of prolonged EFS included pre-surgical ctDNA clearance, non-N2 NSCLC, pCR, squamous tumour histology and nivolumab treatment. These findings provide insights into predictive markers for outcomes with perioperative nivolumab in resectable NSCLC. Potential predictive biomarkers of perioperative nivolumab therapy benefit in non-small cell lung cancer are identified from evaluable participants in the CheckMate 77T trial.