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. 2026 Jan 22:S1533-0028(26)00005-8.
doi: 10.1016/j.clcc.2026.01.003. Online ahead of print.

Lenvatinib Plus Pembrolizumab for Patients With Previously Treated Advanced Colorectal Cancer: Results From the Phase II LEAP-005 Study

Iván Victoria Ruiz  1 , Nataliya V Uboha  2 , Rahima Jamal  3 , Fernando Contreras Mejía  4 , Mónica Ahumada  5 , Seock-Ah Im  6 , Carlos Gomez-Roca  7 , Ronnie Shapira-Frommer  8 , Ruth Perets  9 , Eduardo Yañez  10 , Corina Dutcus  11 , Chinyere E Okpara  12 , Razi Ghori  13 , Fan Jin  13 , Roman Groisberg  13 , Eduardo Castanon  14
Affiliations

Lenvatinib Plus Pembrolizumab for Patients With Previously Treated Advanced Colorectal Cancer: Results From the Phase II LEAP-005 Study

Iván Victoria Ruiz et al. Clin Colorectal Cancer. .

Abstract

Background: Current treatments for patients with previously treated metastatic colorectal cancer (CRC) have poor outcomes. LEAP-005 (ClinicalTrials.gov, NCT03797326) was a multicohort, open-label phase II study evaluating the efficacy and safety of lenvatinib plus pembrolizumab in participants with previously treated selected solid tumors. We report findings from the LEAP-005 CRC cohort.

Patients and methods: Participants aged ≥ 18 years with advanced (metastatic and/or unresectable) CRC with 2 prior lines of systemic therapy were eligible for the CRC cohort of LEAP-005. Participants received oral lenvatinib (20 mg/day) plus intravenous pembrolizumab (200 mg Q3W) combination therapy (Arm 1) or lenvatinib (24 mg/day) monotherapy (Arm 2). Dual primary endpoints were objective response rate (ORR) per RECIST version 1.1 and safety. Secondary endpoints were duration of response (DOR), progression-free survival (PFS), and overall survival (OS).

Results: 135 participants were enrolled in the CRC cohort (Arm 1, n = 105; Arm 2, n = 35). In Arm 1, ORR was 14% (95% CI, 8-23), median PFS was 3.4 (95% CI, 2.1-4.1) months, and OS was 8.7 (95% CI, 7.0-10.0) months. In Arm 2, ORR was 7% (95% CI, 1-22), median PFS was 3.4 (95% CI, 2.1-4.2) months, and OS was 7.7 (95% CI, 5.6-14.8) months. Treatment-related AEs occurred in 96% of participants (grade 3/4, 63%) in Arm 1 and 97% (grade 3/4, 63%) in Arm 2. One participant in Arm 1 died due to treatment-related intestinal perforation.

Conclusion: Lenvatinib plus pembrolizumab demonstrated antitumor activity in participants with advanced CRC with 2 prior lines of treatment. No new safety signals were identified.

Keywords: Gastrointestinal cancers; Immune checkpoint inhibitors; Metastatic disease; Phase II clinical trial; Protein kinase inhibitors.

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Conflict of interest statement

Disclosure I. Victoria: Nothing to declare. N.V. Uboha: Consulting/Advisory Boards: AstraZeneca, Astellas, Strata Oncology, Arcus, Elevation Oncology, Pfizer, BMS, Ipsen, Merck, BeiGene, Eisai. Research Support: Ipsen, EMD Serono, Arcus, Gilead. R. Jamal: Speaker honoraria: BMS, MSD, Novartis, Pfizer. Research grant to institution: MSD, BMS, Iovance Therapeutics. Advisory board: MSD, Novartis, Pfizer, Medison, BMS. F. Contreras Mejía: Speaker honoraria: BMS, MSD, GSK, Axon Pharma, Roche, AstraZeneca, Novartis, Eli Lilly. Advisory board: MSD, BMS, Janssen, Eli Lilly. M. Ahumada: Nothing to declare. S.-A. Im: Advisory role: AstraZeneca, Daiichi-Sankyo, GSK, Hanmi, Idience, Eli Lilly, Merck Sharp & Dohme LLC, a subsidiary of Merck & Co, Inc, Rahway, NJ, USA, Novartis, Pfizer, Bertis and Roche. Grants: AstraZeneca, Boryung Pharm, Daewoong Pharm, Daiichi-Sankyo, Eisai, Pfizer, and Roche. C. Gomez-Roca: Invited speaker: BMS, Pierre Fabre, Roche/Genentech. Consulting/ advisory board: Macomics, Pharmamar. Research grants: Roche/Genentech, Amgen. R. Shapira-Frommer: Speaker honoraria: BMS, Merck Sharp & Dohme LLC, a subsidiary of Merck & Co, Inc, Rahway, NJ, USA, Novartis, Sanofi, Roche, Medison, Neopharm. Research grant to institution: Merck Sharp & Dohme LLC, a subsidiary of Merck & Co, Inc, Rahway, NJ, USA. Advisory board: Merck Sharp & Dohme LLC, a subsidiary of Merck & Co, Inc, Rahway, NJ, USA, VBL Therapeutics, Clovis Oncology. R. Perets: Honoraria: GSK, Neopharm, AstraZeneca. Consulting: 1E therapeutics, Nevia Bio, Yeda. Research funding: 1E therapeutics, Gilead. E. Yañez: Nothing to declare. C. Dutcus: Employee of Eisai Inc, Nutley, NJ, USA. C.E. Okpara: Employee of Eisai Ltd., Hatfield, UK. R. Ghori: Employee of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co, Inc, Rahway, NJ, USA, and owns stock in Merck & Co, Inc, Rahway, NJ, USA. F. Jin: Employee of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co, Inc, Rahway, NJ, USA, and owns stock in Merck & Co, Inc, Rahway, NJ, USA. R. Groisberg: Employee of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co, Inc, Rahway, NJ, USA, and owns stock in Merck & Co, Inc, Rahway, NJ, USA. E. Castanon: Honoraria: BMS, Merck Sharp & Dohme LLC, a subsidiary of Merck & Co, Inc, Rahway, NJ, USA, Pfizer, Roche, AstraZeneca, Novartis, GSK. Advisory board: Merck Sharp & Dohme LLC, a subsidiary of Merck & Co, Inc, Rahway, NJ, USA.

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