Multicenter phase 2 trial of neoadjuvant pembrolizumab plus ramucirumab for PD-L1 positive non-small cell lung cancer

Angiogenesis inhibitors are known to modify tumor immunity. The multicenter phase 2 EAST ENERGY trial in Japan evaluated the neoadjuvant combination of pembrolizumab plus ramucirumab for PD-L1 positive stage IB-IIIA non-small cell lung cancer (NSCLC). Patients received two cycles of pembrolizumab plus ramucirumab every three weeks, followed by surgery scheduled 4 to 8 weeks after the last dose. Major pathologic response (primary end point) was seen in 50.0% of patients (90% CI 31.9-68.1) with pathologic complete response in 25%. Grade 3 adverse events occurred in 37.5%, including immune-related adverse events in 12.5%; there were no grade 4 or 5 adverse events. Exploratory transcriptome and multiplexed immunohistochemistry analyses suggested that tumor with greater CD8⁺ T-cell infiltration and higher expression of effector molecules at baseline showed better sensitivity to treatment. The authors conclude that this new neoadjuvant combination of pembrolizumab and ramucirumab was feasible and active in patients with PD-L1 positive NSCLC.