Lenvatinib plus Pembrolizumab for Patients with Previously Treated Advanced Gastric, Biliary Tract, or Pancreatic Cancer - Results from the Phase II LEAP-005 Study

Sep 22, 2026

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Patients with gastric cancer, biliary tract cancer (BTC), and pancreatic ductal adenocarcinoma (PDAC) experience poor survival and limited second- or later-line options. A multicohort, open-label phase II LEAP-005 study assessed lenvatinib plus pembrolizumab in previously treated solid tumors, targeting VEGF and PD-1 pathways. Participants received lenvatinib 20 mg/day orally with pembrolizumab 200 mg i.v. every 3 weeks, with objective response rate (ORR) and safety as primary endpoints.

LanguageEnglish

CategoryResearch & Report

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Pages14

Reading Time35 min

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Abstract

Purpose

Patients and Methods

Results

Conclusions

Significance

Introduction

RESEARCH ARTICLE [https://doi.org/10.1158/2767-9764.CRC-26-0018](https://doi.org/10.1158/2767-9764.CRC-26-0018) OPEN ACCESS Lenvatinib plus Pembrolizumab for Patients with Previously Treated Advanced Gastric, Biliary Tract, or Pancreatic Cancer: Results from the Phase II LEAP-005 Study Mariano Ponz-Sarvis1, Sun Young Rha2, Carlos A. Gomez-Roca3, Laura Ortega Morn4, Sanjeev Gill5, Giampaolo Tortora6,7, Ravit Geva8, Esma Saada-Bouzid9,10, Armando Santoro11,12, Tae Won Kim13, Daniel Heudobler14, Corina E. Dutcus15, Chinyere E. Okpara16, Razi Ghori17, Yiwei Zhang17, Amir Vajdi17, E.J. Dettman17, Fan Jin17, Roman Groisberg17, and Ronnie Shapira-Frommer18 􀀶 ABSTRACT Purpose: Patients with gastric cancer, biliary tract cancer (BTC), and pancreatic ductal adenocarcinoma (PDAC) have poor survival outcomesand limited second- or later-line treatment options. Certain drugs targeting vascular endothelial growth factor (VEGF) or programmed cell death protein 1 (PD-1) signaling pathways are currently used in these cancers in specific circumstances; however, there remains a need for novel treatment combinations. LEAP-005 is a multicohort, open-label, phase II study that evaluated lenvatinib (multitargeted inhibitor of tyrosine kinases, including VEGF) plus pembrolizumab (anti–PD- 1 monoclonal antibody) in select previously treated solid tumors. Patients and Methods: Participants with previously treated, advanced gastric cancer, BTC, and PDAC were enrolled in cohorts C, F, and G of LEAP-005, respectively, and received lenvatinib 20 mg/day orally plus pembrolizumab 200 mg i.v. every 3 weeks. Primary endpoints were objective response rate (ORR) and safety. Results: Of 99, 102, and 103 total participants enrolled in cohorts C, F, and G, respectively, median times from first dose of study treatment to data cutoff (February 6, 2023) were 23.7, 24.2, and 19.5 months. ORRs (95% confidence interval) by blinded independent central review were 15.2%(8 .7%–23 .8%) in cohort C, 17.6%(10 .8%–26 .4%) in cohort F, and 7.8%(3 .4%–14 .7%) in cohort G. Grade 3 to 5 treatment-related adverse events occurred in 54.5% of participants in cohort C, and grade 3 to 4 (no grade 5) occurred in 60.8% and 59.2% of participants in cohorts F and G, respectively. Conclusions: Lenvatinib plus pembrolizumab demonstrated modest antitumor activity and a manageable safety profile in previously treated, advanced gastric cancer, BTC, and PDAC. Significance: In the phase II LEAP-005 study, lenvatinib plus pembrolizumab showed modest antitumor activity and a manageable safety profile in participants with previously treated gastrointestinal-related cancers. Exploratory analyses in participants with BTC indicated higher ORRs in participants with targetable alterations versus those without. 1Department of Medical Oncology and Program in Solid Tumors, Cancer Center Clnica Universidad de Navarra (CCUN), Cima-Universidad de Navarra, Pamplona, Spain. 2Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Republic of Korea. 3 Institut Universitaire du Cancer de Toulouse Oncopole, Toulouse, France. 4 Department of Medical Oncology, Hospital General Universitario Gregorio Marañn, Madrid, Spain. 5The Alfred Hospital, Melbourne, Australia. 6 Medical Oncology, Fondazione Policlinico AGemelli IRCCS, Rome, Italy. 7 Medical Oncology, Universit Cattolica del Sacro Cuore, Rome, Italy. 8Tel Aviv Sourasky Medical Center, Tel Aviv, Israel. 9 Early Phase Trial Unit, Centre Antoine Lacassagne, Nice, France. 10 Laboratory of Translational Research, Cte d’Azur University, Nice, France. 11 IRCCS, Humanitas Research Hospital, Milan, Italy. 12 Department of Biomedical Sciences, Humanitas University, Milan, Italy. 13 Department of Oncology, Asan Medical Center, University of Ulsan, Seoul, Republic of Korea. 14 University Hospital Regensburg, Regensburg, Germany. 15 Eisai Inc. , Nutley, New Jersey. 16 Eisai Ltd. , Hatfield, United Kingdom. 17 Merck & Co. , Inc. , Rahway, Ne

FAQs

What cancers and patient population were evaluated in LEAP-005?

The study enrolled participants with previously treated advanced gastric cancer, biliary tract cancer (BTC), and pancreatic ductal adenocarcinoma (PDAC) across separate cohorts.

How were lenvatinib and pembrolizumab administered in the trial?

Participants received lenvatinib 20 mg per day orally plus pembrolizumab 200 mg administered intravenously every 3 weeks.

What were the primary endpoints of the phase II study?

Primary endpoints were objective response rate (ORR) and safety, including treatment-related adverse events by grade.

Sep 22, 2026

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