{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T21:48:49Z","timestamp":1792273729225,"version":"4.4.0"},"reference-count":27,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"2","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["JCO"],"published-print":{"date-parts":[[2023,1,10]]},"abstract":"<jats:sec><jats:title>PURPOSE<\/jats:title><jats:p> Limited prospective data are available on sequential immunotherapy and BRAF\/MEK inhibition for BRAFV600-mutant metastatic melanoma. <\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS<\/jats:title><jats:p> SECOMBIT is a randomized, three-arm, noncomparative phase II trial (ClinicalTrials.gov identifier: NCT02631447 ). Patients with untreated, metastatic BRAFV600-mutant melanoma from 37 sites in nine countries were randomly assigned to arm A (encorafenib [450 mg orally once daily] plus binimetinib [45 mg orally twice daily] until progressive disease [PD] -&gt; ipilimumab plus nivolumab [ipilimumab 3 mg\/kg once every 3 weeks and nivolumab 1 mg\/kg once every 3 weeks \u00d7 four cycles -&gt; nivolumab 3 mg\/kg every 2 weeks]), arm B [ipilimumab plus nivolumab until PD -&gt; encorafenib plus binimetinib], or arm C (encorafenib plus binimetinib for 8 weeks -&gt; ipilimumab plus nivolumab until PD -&gt; encorafenib plus binimetinib). The primary end point was overall survival (OS) at 2 years. Secondary end points included total progression-free survival, 3-year OS, best overall response rate, duration of response, and biomarkers in the intent-to-treat population. Safety was analyzed throughout sequential treatment in all participants who received at least one dose of study medication. <\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p> A total of 209 patients were randomly assigned (69 in arm A, 71 in arm B, and 69 in arm C). At a median follow-up of 32.2 (interquartile range, 27.9-41.6) months, median OS was not reached in any arm and more than 30 patients were alive in all arms. Assuming a null hypothesis of median OS of \u2264 15 months, the OS end point was met for all arms. The 2-year and 3-year OS rates were 65% (95% CI, 54 to 76) and 54% (95% CI, 41 to 67) in arm A, 73% (95% CI, 62 to 84) and 62% (95% CI, 48 to 76) in arm B, and 69% (95% CI, 59 to 80) and 60% (95% CI, 58 to 72) in arm C. No new safety signals emerged. <\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSION<\/jats:title><jats:p> Sequential immunotherapy and targeted therapy provide clinically meaningful survival benefits for patients with BRAFV600-mutant melanoma. <\/jats:p><\/jats:sec>","DOI":"10.1200\/jco.21.02961","type":"journal-article","created":{"date-parts":[[2022,9,1]],"date-time":"2022-09-01T20:00:16Z","timestamp":1662062416000},"page":"212-221","update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":235,"title":["Sequencing of Ipilimumab Plus Nivolumab and Encorafenib Plus Binimetinib for Untreated <i>BRAF<\/i>-Mutated Metastatic Melanoma (SECOMBIT): A Randomized, Three-Arm, Open-Label Phase II Trial"],"prefix":"10.1200","volume":"41","clinical-trial-number":[{"clinical-trial-number":"nct02631447","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8322-475X","authenticated-orcid":false,"given":"Paolo A.","family":"Ascierto","sequence":"first","affiliation":[{"name":"Department of Melanoma, Cancer Immunotherapy and Development Therapeutics, I.N.T. 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Pascale\u201d Napoli, Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8846-8959","authenticated-orcid":false,"given":"Mario","family":"Mandal\u00e0","sequence":"additional","affiliation":[{"name":"Department of Oncology and Haematology, Papa Giovanni XXIII Cancer Center Hospital, Bergamo, Italy"},{"name":"University of Perugia, Perugia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6255-5851","authenticated-orcid":false,"given":"Pier Francesso","family":"Ferrucci","sequence":"additional","affiliation":[{"name":"Biotherapy of Tumors Unit, Department of Experimental Oncology, European Institute of Oncology, IRCCS, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7703-790X","authenticated-orcid":false,"given":"Massimo","family":"Guidoboni","sequence":"additional","affiliation":[{"name":"Immunotherapy and Cell 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