Nivolumab (PD-1 blockade) + chemo: ctDNA clearance flags higher pCR and longer EFS in resectable NSCLC

Nivolumab (Opdivo), a PD-1 immune checkpoint inhibitor, was evaluated as perioperative therapy in the Phase 3, double-blind CheckMate 77T trial (NCT04025879): neoadjuvant nivolumab + platinum-doublet chemotherapy (4 cycles) → surgery → adjuvant nivolumab for 1 year vs matched placebo + chemo → surgery → placebo. In this biomarker subset (evaluable: nivolumab n=98; placebo n=92; ~41% of randomized), pre-surgical ctDNA clearance after neoadjuvant therapy was more frequent with nivolumab (66% [50/76]) vs placebo (38% [24/64]), and ctDNA clearance tracked with pCR—50% (25/50) with nivolumab vs 12% (3/24) with placebo; MRD conversion to positive during adjuvant therapy occurred in 8% (4/48) vs 20% (9/44), and all converters recurred. Exploratory genomics suggested perioperative nivolumab prolonged EFS vs placebo in tumors with KEAP1/STK11/CDKN2A/SMARCA4 single or co-alterations (HR 0.48; 95% CI 0.28-0.83), while a machine-learning model ranked pre-surgical ctDNA clearance, non-N2 disease, pCR, squamous histology, and nivolumab treatment as top EFS predictors; in the overall intent-to-treat CheckMate 77T population, EFS favored nivolumab (HR 0.58) with median EFS not reached vs 18.4 months for placebo—well beyond historical surgery±chemo benchmarks and supportive of the now–FDA-approved perioperative nivolumab regimen in EGFR/ALK-negative resectable disease.