Efficacy and Safety of Pembrolizumab (MK-3475) With Lenvatinib (E7080/MK-7902) vs. Docetaxel in Participants With Metastatic Non-Small Cell Lung Cancer (NSCLC) and Progressive Disease (PD) After Platinum Doublet Chemotherapy and Immunotherapy (MK-7902-008/E7080-G000-316/LEAP-008)
Summary
This study will evaluate the efficacy and safety of pembrolizumab (MK-3475) with lenvatinib (E7080/MK-7902) vs. docetaxel in participants with metastatic non-small cell lung cancer (NSCLC) and progressive disease (PD) after platinum doublet chemotherapy and treatment with one prior anti-PD-1/PD-L1 monoclonal antibody (mAb). The primary hypotheses of this study are that pembrolizumab + lenvatinib (compared with docetaxel) prolongs: 1) overall survival (OS); and progression-free survival (PFS) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) based on blinded independent central review (BICR).
Timeline
- Start
- 2019-06-26
- Primary completion
- 2023-08-11
- Completion
- 2024-08-22
Outcome
Missed primary endpoint
registry analysis (superiority test); Pembrolizumab+Lenvatinib vs Docetaxel; p = 0.4342; Hazard Ratio (HR) 0.98 (95% CI 0.78 to 1.23) NCT03976375 ↗
registry analysis (superiority test); Pembrolizumab+Lenvatinib vs Docetaxel; p = 0.1563; Hazard Ratio (HR) 0.89 (95% CI 0.70 to 1.12) NCT03976375 ↗
paper CONCLUSION: Lenvatinib plus pembrolizumab did not improve efficacy versus docetaxel PMID 40473109 ↗
Publications
- Results Leighl NB, Paz-Ares L, Abreu DR, Hui R, Baka S, Bigot F, Nishio M, Smolin A, Ahmed S, Schoenfeld AJ, Daher S, Cortinovis DL, Di Noia V, Linardou H, Gainor JF, Dutcus C, Okpara CE, Deng X, Kush D, Arunachalam A, Song A, Cho BC. 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. J Thorac Oncol. 2025 Oct;20(10):1489-1504. doi: 10.1016/j.jtho.2025.05.020. Epub 2025 Jun 3.
- Xing P, Wang M, Zhao J, Zhong W, Chi Y, Xu Z, Li J. Study protocol: A single-arm, multicenter, phase II trial of camrelizumab plus apatinib for advanced nonsquamous NSCLC previously treated with first-line immunotherapy. Thorac Cancer. 2021 Oct;12(20):2825-2828. doi: 10.1111/1759-7714.14113. Epub 2021 Aug 18.
- Taylor MH, Schmidt EV, Dutcus C, Pinheiro EM, Funahashi Y, Lubiniecki G, Rasco D. The LEAP program: lenvatinib plus pembrolizumab for the treatment of advanced solid tumors. Future Oncol. 2021 Feb;17(6):637-648. doi: 10.2217/fon-2020-0937. Epub 2020 Dec 10.
Drugs
| Evaluation | Drug | Modality | Dose | Route |
|---|---|---|---|---|
| Comparator | Docetaxel | Small molecule | 75 mg/m2 | Intravenous |
| Subject | Lenvatinib | Small molecule | 20 mg | Oral |
| Subject | Lenvatinib | Small molecule | 24 mg | Oral |
| Subject | Pembrolizumab | Monoclonal antibody | 200 mg | Intravenous |