LEAP-008: Lenvatinib Plus Pembrolizumab for Metastatic NSCLC That Has Progressed After an Anti-PD-(L)1 Plus Platinum Chemotherapy.

Background: LEAP-008 (NCT03976375) was an open-label, randomized, phase 3 study of lenvatinib plus pembrolizumab versus docetaxel for metastatic NSCLC that progressed on anti‒programmed cell death protein 1 (PD-1)/programmed cell death ligand 1 (PD-L1) therapy and platinum-containing chemotherapy.

Methods: Participants were randomized 4:4:1 to once-daily lenvatinib 20 mg plus pembrolizumab 200 mg every 3 weeks (maximum 35 cycles), docetaxel 75 mg/m2 every 3 weeks, or once-daily lenvatinib 24 mg. Primary endpoints were overall survival (OS) and progression-free survival (PFS) per RECIST version 1.1 by central review. Superiority of lenvatinib plus pembrolizumab versus docetaxel was assessed at interim analysis 2 for PFS and at final analysis for OS.

Results: Participants (N=422) were randomized to lenvatinib plus pembrolizumab (n=185), docetaxel (n=189), or lenvatinib monotherapy (n=48). Median (95% CI) PFS was 5.6 (4.2‒6.5) months with lenvatinib plus pembrolizumab and 4.2 (3.2‒5.2) months with docetaxel (hazard ratio [HR], 0.89 [95% CI, 0.70‒1.12]; P=0.164). Median (95% CI) OS was 11.3 (9.4‒13.2) versus 12.0 (9.6‒13.7) months (HR, 0.98 [95% CI, 0.78‒1.23]; P=0.434). Rates of treatment-related adverse events (AEs) were 91.7%, 91.0%, and 89.4% with lenvatinib plus pembrolizumab, docetaxel, and lenvatinib, respectively; rates of grade 3 to 5 treatment-related AEs were 59.7%, 48.6%, and 57.4%. Health-related quality of life scores were similar between treatment arms.

Conclusions: Lenvatinib plus pembrolizumab did not improve efficacy versus docetaxel in participants with stage IV NSCLC that progressed on anti‒PD-1/PD-L1 therapy and platinum-containing chemotherapy. There were no unexpected safety signals. More effective therapies are needed for this patient population.