Lenvatinib Plus Pembrolizumab, Pemetrexed, and a Platinum in Chinese Participants with Untreated Metastatic Nonsquamous Non–Small-Cell Lung Cancer: Phase 3 LEAP-006 China Extension Study

Background In the global phase 3 randomized LEAP-006 study (NCT03829319), addition of lenvatinib to pembrolizumab plus chemotherapy did not significantly improve efficacy outcomes in metastatic nonsquamous non-small–cell lung cancer (NSCLC). We present findings from an extension study of LEAP-006 (NCT04716933) including participants from China. Methods Adults (≥18 years) from mainland China with untreated metastatic nonsquamous NSCLC without targetable genetic alterations were randomized 1:1 to lenvatinib 8mg once daily or placebo, plus pembrolizumab 200mg plus cisplatin or carboplatin plus pemetrexed for 4 cycles, followed by lenvatinib or placebo plus pembrolizumab plus pemetrexed for ≤35 cycles. PFS and OS were dual primary endpoints. No alpha was assigned to these analyses. Results Of 201 enrolled participants from China, 101 received lenvatinib plus pembrolizumab and chemotherapy (lenvatinib arm) and 100 to placebo plus pembrolizumab and chemotherapy (placebo arm). Median follow-up was 32.7 months (data cutoff August 11, 2023). Median PFS (95% CI) was 15.3 (12.2‒19.6) and 9.2 (8.2‒12.5) in the lenvatinib and placebo arms, respectively (HR, 0.68; 95% CI, 0.48‒0.97); median OS (95% CI) was 26.6 (22.2‒35.0) months and 22.0 (16.6‒24.8) months (HR, 0.78; 95% CI, 0.54‒1.12). Grade ≥3 treatment-related adverse events occurred in 83.2% and 62.0% of participants in the lenvatinib and placebo arms, respectively; treatment-related AEs that led to death were reported in 7.9% and 3.0% of participants. Conclusions In the China extension of LEAP-006, addition of lenvatinib to pembrolizumab plus chemotherapy was associated with numerical improvements in PFS and OS with manageable safety in previously untreated metastatic nonsquamous NSCLC.