Background
Phase II randomized trial, N=44 with operable stage I–IIIA NSCLC, evaluating neoadjuvant nivolumab vs nivolumab + ipilimumab.
Interventions and follow up
Arm A: Nivolumab 3 mg/kg D1, 15, 29 → surgery → standard of care
Arm B: Nivolumab 3 mg/kg D1, 15, 29 + ipilimumab 1 mg/kg D1 → surgery → standard of care
Primary endpoint: Major pathologic response (MPR), tested vs historical neoadjuvant chemotherapy controls
mFollow up: 22.2 mo
Arm B: Nivolumab 3 mg/kg D1, 15, 29 + ipilimumab 1 mg/kg D1 → surgery → standard of care
Primary endpoint: Major pathologic response (MPR), tested vs historical neoadjuvant chemotherapy controls
mFollow up: 22.2 mo
Results
MPR: 24% (nivo) vs 50% (nivo+ipi)
Pathologic complete response (pCR): 10% vs 38%
Median viable tumor: 50% vs 9%
Immune correlates: nivo+ipi yielded greater frequencies of effector, tissue-resident memory, and effector memory T cells
Pathologic complete response (pCR): 10% vs 38%
Median viable tumor: 50% vs 9%
Immune correlates: nivo+ipi yielded greater frequencies of effector, tissue-resident memory, and effector memory T cells
Adverse events
Overall: Grade 3–5 events 13% (nivo) vs 10% (nivo+ipi)
Surgical: No new surgical safety signals; resection feasible in both arms
Surgical: No new surgical safety signals; resection feasible in both arms
Conclusions
Neoadjuvant nivolumab + ipilimumab enhanced pathologic responses, tumor immune infiltrates, and immunologic memory vs nivolumab alone in operable NSCLC.
Key Limitations
Small phase II (N=44); MPR compared to historical controls rather than a randomized chemotherapy arm; no long-term survival endpoint at this readout.
Clinical Context
Hypothesis-generating; supported dual-checkpoint neoadjuvant strategies but neoadjuvant/perioperative chemoimmunotherapy (CheckMate 816, KEYNOTE-671, AEGEAN) became standard. Nivolumab + ipilimumab is not an established neoadjuvant regimen in NSCLC.