Please use this identifier to cite or link to this item: https://ahro.austin.org.au/austinjspui/handle/1/19259
Full metadata record
DC FieldValueLanguage
dc.contributor.authorDienstmann, Rodrigo-
dc.contributor.authorLassen, Ulrik-
dc.contributor.authorCebon, Jonathan S-
dc.contributor.authorDesai, Jayesh-
dc.contributor.authorBrown, Michael P-
dc.contributor.authorEvers, Stefan-
dc.contributor.authorSu, Fei-
dc.contributor.authorZhang, Weijiang-
dc.contributor.authorBoisserie, Frederic-
dc.contributor.authorLestini, Brian-
dc.contributor.authorSchostack, Kathleen-
dc.contributor.authorMeresse, Valerie-
dc.contributor.authorTabernero, Josep-
dc.date.accessioned2018-09-13T00:21:17Z-
dc.date.available2018-09-13T00:21:17Z-
dc.date.issued2016-04-
dc.identifier.citationTargeted oncology 2016; 11(2): 149-56-
dc.identifier.urihttps://ahro.austin.org.au/austinjspui/handle/1/19259-
dc.description.abstractBRAF mutations are a validated target for cancer therapy. A second-generation BRAF inhibitor with an improved preclinical safety profile (RG7256) was evaluated in a first-in-man study in order to determine the safety, efficacy, pharmacokinetics and pharmacodynamics in patients with BRAF V600-mutated advanced solid tumors. Patients received RG7256 orally over 8 dose levels from 200 mg once a day (QD) to 2400 mg twice a day (BID) (50-, 100- and 150-mg tablets) using a classic 3 + 3 dose escalation design. In total, 45 patients were enrolled; most (87 %) had advanced melanoma (94 % BRAF V600E). RG7256 was rapidly absorbed, with limited accumulation and dose-proportional increase in exposure up to 1950 mg BID. The maximal tolerated dose (MTD) was not reached. The most common drug-related adverse events (AEs) were dyspepsia (20 %), dry skin (18 %), rash (18 %), fatigue (16 %) and nausea (13 %), mainly grade 1. Three patients (7 %) developed cutaneous squamous cell carcinoma. Photosensitivity, arthralgia and increased liver enzyme levels were each observed in only one patient each. Of 44 evaluable patients, 14 (32 %) had a partial response (melanoma and thyroid cancer). At high dose levels (>1200 mg BID), 10 of 16 (63 %) patients had a partial response. A decrease in maximum standardized uptake value (SUVmax) on FDG-PET of ≥25 % was observed in 19 of 37 patients. On-treatment reductions in pERK were documented in eight of ten paired tumor samples. RG7256 has a favorable safety profile compared to other BRAF inhibitors while maintaining clinical activity, and MTD was not reached. The excessive pill burden needed to provide the desired exposure, and thus concerns about patient compliance, limited further development of this agent. Study Identifier: ClinicalTrials.gov (NCT01143753).-
dc.language.isoeng-
dc.titleFirst-in-Man Dose-Escalation Study of the Selective BRAF Inhibitor RG7256 in Patients with BRAF V600-Mutated Advanced Solid Tumors.-
dc.typeJournal Article-
dc.identifier.journaltitleTargeted oncology-
dc.identifier.affiliationP. Vall d'Hebron 119-129, 08035, Barcelona, Spainen
dc.identifier.affiliationGlobal Development, Oncology, Bayer HealthCare Pharmaceuticals, Inc, Whippany, NJ, USAen
dc.identifier.affiliationVall d'Hebron University Hospital, Medical Oncology, Barcelona, Spainen
dc.identifier.affiliationDepartment of Oncology, Rigshospitalet, Copenhagen, Denmarken
dc.identifier.affiliationDepartment of Medical Oncology, Austin Health, Heidelberg, Victoria, Australiaen
dc.identifier.affiliationRoyal Melbourne Hospital, Parkville, Australiaen
dc.identifier.affiliationCancer Clinical Trials Unit, Royal Adelaide Hospital, Centre for Cancer Biology, SA Pathology and University of South Australia, Adelaide, Australiaen
dc.identifier.affiliationPharma Research & Early Development, Roche Innovation Center Zurich, Schlieren, Switzerlanden
dc.identifier.affiliationPharma Research & Early Development, Roche Innovation Center New York, New York, NY, USAen
dc.identifier.affiliationOncology Correlative Science Lead, Novartis Pharmaceutical Corporation, East Hanover, NJ, USAen
dc.identifier.affiliationOncology Global Clinical Research, Bristol-Myers Squibb, New York, NY, USAen
dc.identifier.affiliationPharma Research & Early Development, Roche Innovation Center Basel, Basel, Switzerlanden
dc.identifier.doi10.1007/s11523-015-0381-x-
dc.identifier.pubmedid26310975-
dc.type.austinClinical Trial, Phase I-
dc.type.austinJournal Article-
dc.type.austinMulticenter Study-
local.name.researcherCebon, Jonathan S
item.openairecristypehttp://purl.org/coar/resource_type/c_18cf-
item.cerifentitytypePublications-
item.fulltextNo Fulltext-
item.grantfulltextnone-
item.languageiso639-1en-
item.openairetypeJournal Article-
crisitem.author.deptOlivia Newton-John Cancer Research Institute-
Appears in Collections:Journal articles
Show simple item record

Page view(s)

24
checked on Mar 28, 2024

Google ScholarTM

Check


Items in AHRO are protected by copyright, with all rights reserved, unless otherwise indicated.