{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T08:39:13Z","timestamp":1793176753966,"version":"4.5.0"},"reference-count":30,"publisher":"Elsevier BV","issue":"2","license":[{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"funder":[{"DOI":"10.13039\/100030732","name":"MSD","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100030732","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009947","name":"Merck Sharp and Dohme United Kingdom","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100009947","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003769","name":"Eisai","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003769","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100023368","name":"Eisai Canada","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100023368","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004334","name":"Merck","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004334","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["clinical-colorectal-cancer.com","clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Clinical Colorectal Cancer"],"published-print":{"date-parts":[[2026,6]]},"DOI":"10.1016\/j.clcc.2026.01.003","type":"journal-article","created":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T17:09:12Z","timestamp":1769101752000},"page":"225-238.e2","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":2,"title":["Lenvatinib Plus Pembrolizumab for Patients With Previously Treated Advanced Colorectal Cancer: Results From the Phase II LEAP-005 Study"],"prefix":"10.1016","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8733-6089","authenticated-orcid":false,"given":"Iv\u00e1n","family":"Victoria Ruiz","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nataliya V.","family":"Uboha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rahima","family":"Jamal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernando Contreras","family":"Mej\u00eda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M\u00f3nica","family":"Ahumada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seock-Ah","family":"Im","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos","family":"Gomez-Roca","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronnie","family":"Shapira-Frommer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruth","family":"Perets","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eduardo","family":"Ya\u00f1ez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Corina","family":"Dutcus","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chinyere E.","family":"Okpara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Razi","family":"Ghori","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fan","family":"Jin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roman","family":"Groisberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eduardo","family":"Castanon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"issue":"1","key":"10.1016\/j.clcc.2026.01.003_bib0001","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.annonc.2022.10.003","article-title":"Metastatic colorectal cancer: ESMO clinical practice guideline for diagnosis, treatment and follow-up","volume":"34","author":"Cervantes","year":"2023","journal-title":"Ann Oncol"},{"key":"10.1016\/j.clcc.2026.01.003_bib0002","unstructured":"National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines). Colon cancer. Version 5.2025. https:\/\/www.nccn.org\/guidelines\/guidelines-detail?category=1&id=1428. Accessed February 12, 2026."},{"issue":"9863","key":"10.1016\/j.clcc.2026.01.003_bib0003","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1016\/S0140-6736(12)61900-X","article-title":"Regorafenib monotherapy for previously treated metastatic colorectal cancer (CORRECT): an international, multicentre, randomised, placebo-controlled, phase 3 trial","volume":"381","author":"Grothey","year":"2013","journal-title":"Lancet"},{"issue":"20","key":"10.1016\/j.clcc.2026.01.003_bib0004","doi-asserted-by":"crossref","first-page":"1909","DOI":"10.1056\/NEJMoa1414325","article-title":"Randomized trial of TAS-102 for refractory metastatic colorectal cancer","volume":"372","author":"Mayer","year":"2015","journal-title":"N Engl J Med"},{"issue":"18","key":"10.1016\/j.clcc.2026.01.003_bib0005","doi-asserted-by":"crossref","first-page":"1657","DOI":"10.1056\/NEJMoa2214963","article-title":"Trifluridine-tipiracil and bevacizumab in refractory metastatic colorectal cancer","volume":"388","author":"Prager","year":"2023","journal-title":"N Engl J Med"},{"issue":"10395","key":"10.1016\/j.clcc.2026.01.003_bib0006","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/S0140-6736(23)00772-9","article-title":"Fruquintinib versus placebo in patients with refractory metastatic colorectal cancer (FRESCO-2): an international, multicentre, randomised, double-blind, phase 3 study","volume":"402","author":"Dasari","year":"2023","journal-title":"Lancet"},{"issue":"2","key":"10.1016\/j.clcc.2026.01.003_bib0007","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1615\/CritRevOncog.2020035422","article-title":"Molecular mechanisms of resistance to anti-angiogenic drugs","volume":"26","author":"Filippelli","year":"2021","journal-title":"Crit Rev Oncog"},{"issue":"1","key":"10.1016\/j.clcc.2026.01.003_bib0008","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1007\/s40265-018-1037-9","article-title":"Targeting angiogenesis in colorectal carcinoma","volume":"79","author":"Lopez","year":"2019","journal-title":"Drugs"},{"issue":"10","key":"10.1016\/j.clcc.2026.01.003_bib0009","doi-asserted-by":"crossref","first-page":"1734","DOI":"10.1093\/annonc\/mdn368","article-title":"Polymorphisms in VEGF and IL-8 predict tumor recurrence in stage III colon cancer","volume":"19","author":"Lurje","year":"2008","journal-title":"Ann Oncol"},{"key":"10.1016\/j.clcc.2026.01.003_bib0010","doi-asserted-by":"crossref","DOI":"10.3389\/fgene.2022.943006","article-title":"Pan-cancer analysis of the prognosis and immunological role of AKAP12: a potential biomarker for resistance to anti-VEGF inhibitors","volume":"13","author":"Liang","year":"2022","journal-title":"Front Genet"},{"issue":"2","key":"10.1016\/j.clcc.2026.01.003_bib0011","doi-asserted-by":"crossref","first-page":"e302","DOI":"10.1634\/theoncologist.2019-0407","article-title":"Lenvatinib in management of solid tumors","volume":"25","author":"Hao","year":"2020","journal-title":"Oncologist"},{"issue":"4","key":"10.1016\/j.clcc.2026.01.003_bib0012","doi-asserted-by":"crossref","DOI":"10.1136\/esmoopen-2020-000776","article-title":"Phase II study of lenvatinib for metastatic colorectal cancer refractory to standard chemotherapy: the LEMON study (NCCH1503)","volume":"5","author":"Iwasa","year":"2020","journal-title":"ESMO Open"},{"issue":"6","key":"10.1016\/j.clcc.2026.01.003_bib0013","doi-asserted-by":"crossref","first-page":"637","DOI":"10.2217\/fon-2020-0937","article-title":"The LEAP program: lenvatinib plus pembrolizumab for the treatment of advanced solid tumors","volume":"17","author":"Taylor","year":"2021","journal-title":"Future Oncol"},{"issue":"2","key":"10.1016\/j.clcc.2026.01.003_bib0014","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1158\/0008-5472.CAN-20-2426","article-title":"Inhibition of FGFR reactivates IFN\u03b3 signaling in tumor cells to enhance the combined antitumor activity of lenvatinib with anti-PD-1 antibodies","volume":"82","author":"Adachi","year":"2022","journal-title":"Cancer Res"},{"issue":"2","key":"10.1016\/j.clcc.2026.01.003_bib0015","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0212513","article-title":"Lenvatinib plus anti-PD-1 antibody combination treatment activates CD8+ T cells through reduction of tumor-associated macrophage and activation of the interferon pathway","volume":"14","author":"Kato","year":"2019","journal-title":"PLoS One"},{"issue":"6","key":"10.1016\/j.clcc.2026.01.003_bib0016","doi-asserted-by":"crossref","DOI":"10.1177\/10781552231178461","article-title":"Combined use of pembrolizumab and lenvatinib: a review","volume":"29","author":"Eisinger","year":"2023","journal-title":"J Oncol Pharm Pract"},{"issue":"23","key":"10.1016\/j.clcc.2026.01.003_bib0017","doi-asserted-by":"crossref","first-page":"2207","DOI":"10.1056\/NEJMoa2017699","article-title":"Pembrolizumab in microsatellite-instability-high advanced colorectal cancer","volume":"383","author":"Andre","year":"2020","journal-title":"N Engl J Med"},{"issue":"5","key":"10.1016\/j.clcc.2026.01.003_bib0018","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1016\/S1470-2045(22)00197-8","article-title":"Pembrolizumab versus chemotherapy for microsatellite instability-high or mismatch repair-deficient metastatic colorectal cancer (KEYNOTE-177): final analysis of a randomised, open-label, phase 3 study","volume":"23","author":"Diaz","year":"2022","journal-title":"Lancet Oncol"},{"key":"10.1016\/j.clcc.2026.01.003_bib0019","unstructured":"Keytruda (pembrolizumab). Full prescribing information. Rahway, NJ, USA,: Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc.; 2026. https:\/\/www.merck.com\/product\/usa\/pi_circulars\/k\/keytruda\/keytruda_pi.pdf. Accessed February 12, 2026."},{"issue":"1","key":"10.1016\/j.clcc.2026.01.003_bib0020","doi-asserted-by":"crossref","DOI":"10.1136\/jitc-2021-003091","article-title":"Tumor mutational burden predicts the efficacy of pembrolizumab monotherapy: a pan-tumor retrospective analysis of participants with advanced solid tumors","volume":"10","author":"Cristescu","year":"2022","journal-title":"J Immunother Cancer"},{"issue":"Number 3 suppl","key":"10.1016\/j.clcc.2026.01.003_bib0021","article-title":"LEAP-005: a phase II multicohort study of lenvatinib plus pembrolizumab in patients with previously treated selected solid tumors-results from the colorectal cancer cohort","volume":"39","author":"Gomez-Roca","year":"2021","journal-title":"J Clin Oncol."},{"issue":"6","key":"10.1016\/j.clcc.2026.01.003_bib0022","doi-asserted-by":"crossref","first-page":"849","DOI":"10.1016\/S1470-2045(19)30027-0","article-title":"Atezolizumab with or without cobimetinib versus regorafenib in previously treated metastatic colorectal cancer (IMblaze370): a multicentre, open-label, phase 3, randomised, controlled trial","volume":"20","author":"Eng","year":"2019","journal-title":"Lancet Oncol"},{"issue":"18","key":"10.1016\/j.clcc.2026.01.003_bib0023","doi-asserted-by":"crossref","first-page":"2053","DOI":"10.1200\/JCO.19.03296","article-title":"Regorafenib plus nivolumab in patients with advanced gastric or colorectal cancer: an open-label, dose-escalation, and dose-expansion phase ib trial (REGONIVO, EPOC1603)","volume":"38","author":"Fukuoka","year":"2020","journal-title":"J Clin Oncol"},{"key":"10.1016\/j.clcc.2026.01.003_bib0024","doi-asserted-by":"crossref","DOI":"10.1016\/j.eclinm.2023.101917","article-title":"Regorafenib plus nivolumab in patients with mismatch repair-proficient\/microsatellite stable metastatic colorectal cancer: a single-arm, open-label, multicentre phase 2 study","volume":"58","author":"Fakih","year":"2023","journal-title":"EClinicalMedicine"},{"issue":"5","key":"10.1016\/j.clcc.2026.01.003_bib0025","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1001\/jamaoncol.2022.7845","article-title":"Regorafenib, ipilimumab, and nivolumab for patients with microsatellite stable colorectal cancer and disease progression with prior chemotherapy: a phase 1 nonrandomized clinical trial","volume":"9","author":"Fakih","year":"2023","journal-title":"JAMA Oncol"},{"key":"10.1016\/j.clcc.2026.01.003_bib0026","doi-asserted-by":"crossref","first-page":"S178","DOI":"10.1016\/j.annonc.2023.04.014","article-title":"LBA-4 results from an expanded phase 1 trial of botensilimab (BOT), a multifunctional anti-CTLA-4, plus balstilimab (BAL; anti-PD-1) for metastatic heavily pretreated microsatellite stable colorectal cancer (MSS CRC)","volume":"34","author":"Bullock","year":"2023","journal-title":"Ann Oncol"},{"issue":"suppl 4","key":"10.1016\/j.clcc.2026.01.003_bib0027","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1200\/JCO.2022.40.4_suppl.135","article-title":"Phase II trial of cabozantinib (Cabo) plus durvalumab (Durva) in chemotherapy refractory patients with advanced mismatch repair proficient\/microsatellite stable (pMMR\/MSS) colorectal cancer (CRC): CAMILLA CRC cohort results [abstract]","volume":"40","author":"Saeed","year":"2022","journal-title":"J Clin Oncol"},{"issue":"24","key":"10.1016\/j.clcc.2026.01.003_bib0028","doi-asserted-by":"crossref","first-page":"2918","DOI":"10.1200\/JCO.23.02736","article-title":"Lenvatinib plus pembrolizumab versus standard of care for previously treated metastatic colorectal cancer: final analysis of the randomized, open-label, phase III LEAP-017 study","volume":"42","author":"Kawazoe","year":"2024","journal-title":"J Clin Oncol"},{"key":"10.1016\/j.clcc.2026.01.003_bib0029","unstructured":"KEYTRUDA (pembrolizumab). Summary of product characteristics. The Netherlands: Merck Sharp & Dohme B.V.; 2023. https:\/\/www.ema.europa.eu\/en\/documents\/product-information\/keytruda-epar-product-information_en.pdf. Accessed February 12, 2026."},{"key":"10.1016\/j.clcc.2026.01.003_bib0030","unstructured":"Lenvima (lenvatinib). Full prescribing information. Full Prescribing Information. Nutley, NJ, USA: Eisai Inc.; 2025. https:\/\/www.lenvima.com\/-\/media\/Project\/EISAI\/Lenvima\/PDF\/prescribing-information.pdf. Accessed February 12, 2026."}],"container-title":["Clinical Colorectal Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1533002826000058?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1533002826000058?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T08:25:30Z","timestamp":1793175930000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1533002826000058"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6]]},"references-count":30,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2026,6]]}},"alternative-id":["S1533002826000058"],"URL":"https:\/\/doi.org\/10.1016\/j.clcc.2026.01.003","relation":{},"ISSN":["1533-0028"],"issn-type":[{"value":"1533-0028","type":"print"}],"subject":[],"published":{"date-parts":[[2026,6]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Lenvatinib Plus Pembrolizumab for Patients With Previously Treated Advanced Colorectal Cancer: Results From the Phase II LEAP-005 Study","name":"articletitle","label":"Article Title"},{"value":"Clinical Colorectal Cancer","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.clcc.2026.01.003","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2026 Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.","name":"copyright","label":"Copyright"}]}}