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dc.contributor.authorDesai, Jayesh-
dc.contributor.authorGan, Hui K-
dc.contributor.authorBarrow, Catherine-
dc.contributor.authorJameson, Michael-
dc.contributor.authorAtkinson, Victoria-
dc.contributor.authorHaydon, Andrew-
dc.contributor.authorMillward, Michael-
dc.contributor.authorBegbie, Stephen-
dc.contributor.authorBrown, Michael-
dc.contributor.authorMarkman, Ben-
dc.contributor.authorPatterson, William-
dc.contributor.authorHill, Andrew-
dc.contributor.authorHorvath, Lisa-
dc.contributor.authorNagrial, Adnan-
dc.contributor.authorRichardson, Gary-
dc.contributor.authorJackson, Christopher-
dc.contributor.authorFriedlander, Michael-
dc.contributor.authorParente, Phillip-
dc.contributor.authorTran, Ben-
dc.contributor.authorWang, Lai-
dc.contributor.authorChen, Yunxin-
dc.contributor.authorTang, Zhiyu-
dc.contributor.authorHuang, Wendy-
dc.contributor.authorWu, John-
dc.contributor.authorZeng, Dewan-
dc.contributor.authorLuo, Lusong-
dc.contributor.authorSolomon, Benjamin-
dc.identifier.citationJournal of Clinical Oncology 2020; 38(19): 2140-2150-
dc.description.abstractLifirafenib is an investigational, reversible inhibitor of B-RAFV600E, wild-type A-RAF, B-RAF, C-RAF, and EGFR. This first-in-human, phase I, dose-escalation/dose-expansion study evaluated the safety, tolerability, and efficacy of lifirafenib in patients with B-RAF- or K-RAS/N-RAS-mutated solid tumors. During dose escalation, adult patients with histologically/cytologically confirmed advanced solid tumors received escalating doses of lifirafenib. Primary end points were safety/tolerability during dose escalation and objective response rate in preselected patients with B-RAF and K-RAS/N-RAS mutations during dose expansion. The maximum tolerated dose was established as 40 mg/d; dose-limiting toxicities included reversible thrombocytopenia and nonhematologic toxicity. Across the entire study, the most common grade ≥ 3 treatment-emergent adverse events were hypertension (n = 23; 17.6%) and fatigue (n = 13; 9.9%). One patient with B-RAF-mutated melanoma achieved complete response, and 8 patients with B-RAF mutations had confirmed objective responses: B-RAFV600E/K melanoma (n = 5, including 1 patient treated with prior B-RAF/MEK inhibitor therapy), B-RAFV600E thyroid cancer/papillary thyroid cancer (PTC; n = 2), and B-RAFV600E low-grade serous ovarian cancer (LGSOC; n = 1). One patient with B-RAF-mutated non-small-cell lung cancer (NSCLC) had unconfirmed partial response (PR). Patients with K-RAS-mutated endometrial cancer and K-RAS codon 12-mutated NSCLC had confirmed PR (n = 1 each). No responses were seen in patients with K-RAS/N-RAS-mutated colorectal cancer (n = 20). Lifirafenib is a novel inhibitor of key RAF family kinases and EGFR, with an acceptable risk-benefit profile and antitumor activity in patients with B-RAFV600-mutated solid tumors, including melanoma, PTC, and LGSOC, as well as K-RAS-mutated NSCLC and endometrial carcinoma. Future comparisons with first-generation B-RAF inhibitors and exploration of lifirafenib alone or as combination therapy in patients with selected RAS mutations who are resistant/refractory to first-generation B-RAF inhibitors are warranted.-
dc.titlePhase I, Open-Label, Dose-Escalation/Dose-Expansion Study of Lifirafenib (BGB-283), an RAF Family Kinase Inhibitor, in Patients With Solid Tumors.-
dc.typeJournal Article-
dc.identifier.journaltitleJournal of Clinical Oncology-
dc.identifier.affiliationWellington Hospital, Wellington, New Zealanden
dc.identifier.affiliationPrincess Alexandra Hospital, Woolloongabba, Queensland, Australiaen
dc.identifier.affiliationDunedin Hospital, Dunedin, New Zealanden
dc.identifier.affiliationWaikato Hospital and University of Auckland Waikato Clinical Campus, Hamilton, New Zealanden
dc.identifier.affiliationBeiGene (Beijing) Co, Beijing, People's Republic of Chinaen
dc.identifier.affiliationOlivia Newton-John Cancer Wellness and Research Centre, Austin Health, Heidelberg, Victoria, Australiaen
dc.identifier.affiliationLa Trobe University School of Cancer Medicine, Heidelberg, Victoria, Australiaen
dc.identifier.affiliationDepartment of Medicine, Austin Health, The University of Melbourne, Heidelberg, Victoria, Australiaen
dc.identifier.affiliationPeter MacCallum Cancer Center, Melbourne, Victoria, Australiaen
dc.identifier.affiliationRoyal Melbourne Hospital, Melbourne, Victoria, Australiaen
dc.identifier.affiliationEastern Health Monash University, Box Hill Hospital, Box Hill, Victoria, Australiaen
dc.identifier.affiliationPrince of Wales Hospital, Randwick, New South Wales, Australiaen
dc.identifier.affiliationCabrini Health, Malvern, Victoria, Australiaen
dc.identifier.affiliationWestmead Hospital, Westmead, New South Wales, Australiaen
dc.identifier.affiliationChris O'Brien Lifehouse, Camperdown, New South Wales, Australiaen
dc.identifier.affiliationTasman Oncology Research, Southport, Queensland, Australiaen
dc.identifier.affiliationThe Queen Elizabeth Hospital, Woodville South, South Australia, Australiaen
dc.identifier.affiliationMonash Health and Monash University, Clayton, Victoria, Australiaen
dc.identifier.affiliationRoyal Adelaide Hospital, Adelaide, South Australia, Australiaen
dc.identifier.affiliationMid North Coast Cancer Institute, Port Macquarie, New South Wales, Australiaen
dc.identifier.affiliationLinear Clinical Research, Nedlands, Western Australia, Australiaen
dc.identifier.affiliationThe Alfred, Melbourne, Victoria, Australiaen
dc.identifier.affiliationBeiGene USA, San Mateo, CA-
dc.type.austinJournal Article-, Hui K
item.openairetypeJournal Article-
item.fulltextNo Fulltext-
item.grantfulltextnone- Oncology- Newton-John Cancer Wellness and Research Centre-
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