{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T20:53:06Z","timestamp":1790974386950,"version":"4.1.0"},"reference-count":35,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"10","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["JCO Precis Oncol"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:sec>\n                    <jats:title>PURPOSE<\/jats:title>\n                    <jats:p>\n                      Tovorafenib is an oral, selective, CNS-penetrant, type II inhibitor of BRAF and CRAF.\n                      <jats:italic toggle=\"yes\">BRAF<\/jats:italic>\n                      fusions and\n                      <jats:italic toggle=\"yes\">CRAF\/RAF1<\/jats:italic>\n                      fusions and amplifications are rare oncogenic drivers in many solid tumors. The phase II DAY101-102a substudy of FIRELIGHT-1 (ClinicalTrials.gov identifier:\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/www.clinicaltrials.gov\/ct2\/show\/NCT04985604\">NCT04985604<\/jats:ext-link>\n                      ) investigated the efficacy and safety of tovorafenib monotherapy in recurrent\/refractory solid tumors with structural alterations in\n                      <jats:italic toggle=\"yes\">BRAF<\/jats:italic>\n                      or\n                      <jats:italic toggle=\"yes\">CRAF<\/jats:italic>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>PATIENTS AND METHODS<\/jats:title>\n                    <jats:p>\n                      Patients \u226512 years of age with a recurrent\/refractory solid tumor with a\n                      <jats:italic toggle=\"yes\">BRAF<\/jats:italic>\n                      fusion or\n                      <jats:italic toggle=\"yes\">CRAF<\/jats:italic>\n                      fusion or amplification were enrolled into a melanoma cohort or tumor-agnostic cohort. The primary end point was overall response rate (ORR), as assessed by investigators. Tovorafenib was administered at 600 mg once weekly (adult dose), continuously, in 28-day cycles.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      Twenty-three patients were enrolled; eight in the melanoma cohort and 15 in the tumor-agnostic cohort. The median age was 53 years (range, 21-71), and 57% of patients had \u22652 lines of prior therapy. Fourteen patients had tumors with\n                      <jats:italic toggle=\"yes\">BRAF<\/jats:italic>\n                      fusion, six\n                      <jats:italic toggle=\"yes\">CRAF<\/jats:italic>\n                      fusion, two\n                      <jats:italic toggle=\"yes\">CRAF<\/jats:italic>\n                      amplification, and one\n                      <jats:italic toggle=\"yes\">CRAF<\/jats:italic>\n                      fusions and amplification. The median duration of tovorafenib treatment was 5.3 months (range, 0.8-22.5). The ORR was 43% (10\/23 patients), including 50% (4\/8) in patients with melanoma and 40% (6\/15) in patients with other tumors. The median time to response was 1.8 months. The median duration of response was 9.2 months. The most common treatment-related adverse events (any grade) were anemia (39%), pruritus (30%), increased creatine phosphokinase (26%), and rash (26%).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSION<\/jats:title>\n                    <jats:p>\n                      Tovorafenib demonstrated single-agent clinical activity in solid tumors with\n                      <jats:italic toggle=\"yes\">BRAF<\/jats:italic>\n                      fusions or\n                      <jats:italic toggle=\"yes\">CRAF<\/jats:italic>\n                      fusions or amplification and had a manageable safety profile. Tovorafenib may offer a new targeted treatment option for adult patients with tumors harboring these rare genomic driver alterations.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1200\/po-25-01187","type":"journal-article","created":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T19:59:07Z","timestamp":1790971147000},"update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":0,"title":["Type II RAF Inhibitor Tovorafenib in Recurrent\/Refractory Melanoma or Other Solid Tumors With\n                    <i>BRAF<\/i>\n                    Fusions or\n                    <i>CRAF\/RAF1<\/i>\n                    Fusions or Amplification: Phase II FIRELIGHT-1 Substudy"],"prefix":"10.1200","volume":"10","clinical-trial-number":[{"clinical-trial-number":"nct04985604","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7531-343X","authenticated-orcid":true,"given":"Maria","family":"Vieito","sequence":"first","affiliation":[{"name":"Hospital Universitari Vall d'Hebron, Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4412-7842","authenticated-orcid":true,"given":"Elena Garralda","family":"Cabanas","sequence":"additional","affiliation":[{"name":"Hospital Universitari Vall d'Hebron, Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2253-2206","authenticated-orcid":true,"given":"Inderjit","family":"Mehmi","sequence":"additional","affiliation":[{"name":"The Angeles Clinic &amp; Research Institute, Inc, Los Angeles, 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