LEAP-008: Lenvatinib Plus Pembrolizumab for Metastatic NSCLC That Has Progressed After an Anti-Programmed Cell Death Protein 1 or Anti-Programmed Cell Death Ligand 1 Plus Platinum Chemotherapy.

backgroundLEAP-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 or anti‒programmed cell death ligand 1 therapy and platinum-containing chemotherapy.

methodsParticipants were randomized 4:4:1 to once-daily lenvatinib 20 mg plus pembrolizumab 200 mg every 3 weeks (maximum 35 cycles), docetaxel 75 mg/m

resultsParticipants (N = 422) were randomized to lenvatinib plus pembrolizumab (n = 185), docetaxel (n = 189), or lenvatinib monotherapy (n = 48). The median (95% confidence interval [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, 0.89 [95% CI: 0.70‒1.12]; p = 0.164). The median (95% CI) OS was 11.3 (9.4‒13.2) versus 12.0 (9.6‒13.7) months (hazard ratio, 0.98 [95% CI: 0.78‒1.23]; p = 0.434). Rates of treatment-related adverse events were 91.7%, 91.0%, and 89.4% with lenvatinib plus pembrolizumab, docetaxel, and lenvatinib, respectively; the rates of grade 3 to 5 treatment-related adverse events were 59.7%, 48.6%, and 57.4%. Health-related quality of life scores were similar between treatment arms.

conclusionLenvatinib plus pembrolizumab did not improve efficacy versus docetaxel in participants with stage IV NSCLC that progressed on anti‒programmed cell death protein 1 or anti-programmed cell death ligand 1 therapy and platinum-containing chemotherapy. There were no unexpected safety signals. More effective therapies are needed for this patient population.