{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T19:39:24Z","timestamp":1790624364017,"version":"4.1.0"},"reference-count":34,"publisher":"Wiley","issue":"16","license":[{"start":{"date-parts":[[2025,8,13]],"date-time":"2025-08-13T00:00:00Z","timestamp":1755043200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["acsjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer"],"published-print":{"date-parts":[[2025,8,15]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Patients with recurrent glioblastoma (GBM) have a poor prognosis and limited treatment options. The authors report the efficacy and safety of lenvatinib plus pembrolizumab in participants with recurrent GBM enrolled in the phase 2, multicohort LEAP\u2010005 study (NCT03797326).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Eligible participants had histologically confirmed GBM (World Health Organization grade IV) with disease progression since previous treatment, and one or more prior lines of therapy. Participants were enrolled regardless of tumor programmed cell death ligand 1 (PD\u2010L1) status and received oral lenvatinib 20 mg per day plus intravenous pembrolizumab 200 mg every 3 weeks. The dual primary end points were objective response rate (ORR; per Response Assessment in Neuro\u2010Oncology by blinded independent central review) and safety.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A total of 101 participants were enrolled, with median (range) follow\u2010up of 23.7 (16.4\u201246.6) months. The median (range) duration of treatment with lenvatinib plus pembrolizumab was 3.4 (0.3\u201232.2) months. The ORR (95% confidence interval [CI]) was 20% (13%\u201229%), with 20 participants achieving a partial response, and the median (range) duration of response was 3.7 (1.4+ to 27.6) months. Median (95% CI) progression\u2010free survival was 3.0 (2.7\u20124.0) months and median (95% CI) overall survival was 8.6 (7.4\u201210.8) months. Responses were observed regardless of PD\u2010L1 status. Treatment\u2010related adverse events occurred in 93 participants (92%; grade 3\u20125, <jats:italic>n<\/jats:italic>\u00a0=\u00a041 [41%]). Two participants died due to treatment\u2010related adverse events (intestinal perforation and pneumonitis).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The combination of lenvatinib plus pembrolizumab demonstrated antitumor activity in a small subpopulation of participants with recurrent GBM as second\u2010line or later treatment. The safety profile was manageable.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cncr.70015","type":"journal-article","created":{"date-parts":[[2025,8,14]],"date-time":"2025-08-14T06:05:16Z","timestamp":1755151516000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Lenvatinib plus pembrolizumab for patients with previously treated select solid tumors: Results from the phase 2 LEAP\u2010005 study recurrent glioblastoma cohort"],"prefix":"10.1002","volume":"131","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2512-4531","authenticated-orcid":false,"given":"Sun Young","family":"Rha","sequence":"first","affiliation":[{"name":"Division of Medical Oncology Yonsei Cancer Center Yonsei University College of Medicine Songdang Institute for Cancer Research  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eduardo","family":"Castanon","sequence":"additional","affiliation":[{"name":"Department of Oncology Cl\u00ednica Universidad de Navarra  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanjeev","family":"Gill","sequence":"additional","affiliation":[{"name":"Medical Oncology Department Alfred Hospital  Melbourne Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helene","family":"Senellart","sequence":"additional","affiliation":[{"name":"Integrated Center for Oncology Centre Ren\u00e9 Gauducheau  Saint Herblain France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juanita","family":"Lopez","sequence":"additional","affiliation":[{"name":"Phase I Drug Development Unit The Royal Marsden Hospital and The Institute of Cancer Research  Sutton UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iv\u00e1n","family":"M\u00e1rquez\u2010Rodas","sequence":"additional","affiliation":[{"name":"Hospital General Universitario Gregorio Mara\u00f1on and Universidad Complutense  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iv\u00e1n","family":"Victoria","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology IDIBAPS, Hospital Cl\u00ednic  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6145-4426","authenticated-orcid":false,"given":"Tae Min","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Seoul National University Hospital  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zarnie","family":"Lwin","sequence":"additional","affiliation":[{"name":"Royal Brisbane and Women\u2019s Hospital University of Queensland  Herston Queensland Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael C.","family":"Burger","sequence":"additional","affiliation":[{"name":"Goethe University Frankfurt University Hospital Dr. Senckenberg Institute of Neurooncology  Frankfurt Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5264-1251","authenticated-orcid":false,"given":"Matteo","family":"Simonelli","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences Humanitas University  Milan Italy"},{"name":"Department of Medical Oncology and Hematology IRCCS Humanitas Research Hospital  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippe A.","family":"Cassier","sequence":"additional","affiliation":[{"name":"D\u00e9partement de Canc\u00e9rologie M\u00e9dicale Centre L\u00e9on B\u00e9rard  Lyon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2079-9177","authenticated-orcid":false,"given":"Andrew E.","family":"Hendifar","sequence":"additional","affiliation":[{"name":"Department of Medicine Division of Hematology and Oncology Cedars\u2010Sinai Medical Center Cedars\u2010Sinai Samuel Oschin Comprehensive Cancer Institute  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo A.","family":"Ascierto","sequence":"additional","affiliation":[{"name":"Department of Melanoma Cancer Immunotherapy and Development Therapeutics Istituto Nazionale Tumori IRCCS \u201cFondazione G. 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