{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T16:05:24Z","timestamp":1792598724932,"version":"4.5.0"},"reference-count":43,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"1","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["JCO"],"published-print":{"date-parts":[[2023,1,1]]},"abstract":"<jats:sec><jats:title>PURPOSE<\/jats:title><jats:p> Effective treatments are needed for melanoma that progresses on inhibitors of programmed cell death protein-1 (PD-1) or its ligand (PD-L1). We conducted the phase II LEAP-004 study to evaluate the combination of the multikinase inhibitor lenvatinib and the PD-1 inhibitor pembrolizumab in this population (ClinicalTrials.gov identifier: NCT03776136 ). <\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS<\/jats:title><jats:p> Eligible patients with unresectable stage III-IV melanoma with confirmed progressive disease (PD) within 12 weeks of the last dose of a PD-1\/L1 inhibitor given alone or with other therapies, including cytotoxic T-cell lymphocyte\u2013associated antigen 4 (CTLA-4) inhibitors, received lenvatinib 20 mg orally once daily plus \u2264 35 doses of pembrolizumab 200 mg intravenously once every 3 weeks until PD or unacceptable toxicity. The primary end point was objective response rate (ORR) per RECIST, version 1.1, by independent central review. <\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p> A total of 103 patients were enrolled and treated. The median study follow-up was 15.3 months. ORR in the total population was 21.4% (95% CI, 13.9 to 30.5), with three (2.9%) complete responses and 19 (18.4%) partial responses. The median duration of response was 8.3 months (range, 3.2-15.9+). ORR was 33.3% in the 30 patients with PD on prior anti\u2013PD-1 plus anti\u2013CTLA-4 therapy. The median progression-free survival and overall survival in the total population were 4.2 months (95% CI, 3.8 to 7.1) and 14.0 months (95% CI, 10.8 to not reached), respectively. Grade 3-5 treatment-related adverse events occurred in 47 (45.6%) patients, most commonly hypertension (21.4%); one patient died from a treatment-related event (decreased platelet count). <\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSION<\/jats:title><jats:p> Lenvatinib plus pembrolizumab provides clinically meaningful, durable responses in patients with advanced melanoma with confirmed PD on prior PD-1\/L1 inhibitor-based therapy, including those with PD on anti\u2013PD-1 plus anti\u2013CTLA-4 therapy. The safety profile was as expected. These data support lenvatinib plus pembrolizumab as a potential regimen for this population of high unmet need. <\/jats:p><\/jats:sec>","DOI":"10.1200\/jco.22.00221","type":"journal-article","created":{"date-parts":[[2022,7,22]],"date-time":"2022-07-22T19:59:36Z","timestamp":1658519976000},"page":"75-85","update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":125,"title":["Phase II LEAP-004 Study of Lenvatinib Plus Pembrolizumab for Melanoma With Confirmed Progression on a Programmed Cell Death Protein-1 or Programmed Death Ligand 1 Inhibitor Given as Monotherapy or in Combination"],"prefix":"10.1200","volume":"41","clinical-trial-number":[{"clinical-trial-number":"nct03776136","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2896-1957","authenticated-orcid":false,"given":"Ana","family":"Arance","sequence":"first","affiliation":[{"name":"Hospital Clinic Barcelona and IDIBAPS, Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5333-0535","authenticated-orcid":false,"given":"Luis","family":"de la Cruz-Merino","sequence":"additional","affiliation":[{"name":"Hospital Universitario Virgen Macarena, Seville, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teresa M.","family":"Petrella","sequence":"additional","affiliation":[{"name":"Sunnybrook Health Sciences Centre, Toronto, ON, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rahima","family":"Jamal","sequence":"additional","affiliation":[{"name":"Centre Hospitalier de l\u2019Universit\u00e9 de Montr\u00e9al (CHUM), Centre de recherche du CHUM, Montr\u00e9al, QC, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3864-5958","authenticated-orcid":false,"given":"Lars","family":"Ny","sequence":"additional","affiliation":[{"name":"University of Gothenburg and Sahlgrenska University Hospital, Gothenburg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1818-7008","authenticated-orcid":false,"given":"Ana","family":"Carneiro","sequence":"additional","affiliation":[{"name":"Sk\u00e5ne University Hospital Comprehensive Cancer Center and Lund University, Lund, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alfonso","family":"Berrocal","sequence":"additional","affiliation":[{"name":"Hospital General Universitario de Valencia, Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2476-668X","authenticated-orcid":false,"given":"Ivan","family":"M\u00e1rquez-Rodas","sequence":"additional","affiliation":[{"name":"Hospital General Universitario Gregorio Mara\u00f1\u00f3n and CIBERONC, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Spreafico","sequence":"additional","affiliation":[{"name":"Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, ON, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victoria","family":"Atkinson","sequence":"additional","affiliation":[{"name":"Princess Alexandra Hospital, University of Queensland, Brisbane, QLD, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernanda","family":"Costa Svedman","sequence":"additional","affiliation":[{"name":"Karolinska University Hospital, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Mant","sequence":"additional","affiliation":[{"name":"Eastern Health, Monash University, Melbourne, VIC, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammad A.","family":"Khattak","sequence":"additional","affiliation":[{"name":"Fiona Stanley Hospital, Murdoch and Edith Cowan University, Perth, WA, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4010-2012","authenticated-orcid":false,"given":"Catalin","family":"Mihalcioiu","sequence":"additional","affiliation":[{"name":"Royal Victoria Hospital, McGill University, Montr\u00e9al, QC, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sekwon","family":"Jang","sequence":"additional","affiliation":[{"name":"Inova Schar Cancer Institute, Fairfax, VA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C. 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