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dc.contributorVall d'Hebron Barcelona Hospital Campus
dc.contributor.authorTrippett, Tanya
dc.contributor.authorToledano, Helen
dc.contributor.authorCampbell Hewson, Quentin
dc.contributor.authorVerschuur, Arnauld
dc.contributor.authorLangevin, Anne‑Marie
dc.contributor.authorAerts, Isabelle
dc.contributor.authorGallego Melcón, Soledad
dc.date.accessioned2022-09-12T09:23:00Z
dc.date.available2022-09-12T09:23:00Z
dc.date.issued2022-05
dc.identifier.citationTrippett T, Toledano H, Campbell Hewson Q, Verschuur A, Langevin AM, Aerts I, et al. Cobimetinib in Pediatric and Young Adult Patients with Relapsed or Refractory Solid Tumors (iMATRIX-cobi): A Multicenter, Phase I/II Study. Target Oncol. 2022 May;17(3):283–93.
dc.identifier.issn1776-260X
dc.identifier.urihttp://hdl.handle.net/11351/8147
dc.descriptionCobimetinib; Pediatrics; Refractory Solid Tumors
dc.description.abstractBackground: The MAPK pathway is an emerging target across a number of adult and pediatric tumors. Targeting the downstream effector of MAPK, MEK1, is a proposed strategy to control the growth of MAPK-dependent tumors. Objective: iMATRIX-cobi assessed the safety, pharmacokinetics, and anti-tumor activity of cobimetinib, a highly selective MEK inhibitor, in children and young adults with relapsed/refractory solid tumors. Patients and methods: This multicenter Phase I/II study enrolled patients aged 6 months to < 30 years with solid tumors with known/expected MAPK pathway involvement. Patients received cobimetinib tablet or suspension formulation on Days 1-21 of a 28-day cycle. Dose escalation followed a rolling 6 design. The primary endpoint was safety; secondary endpoints were pharmacokinetics and anti-tumor activity. Results: Of 56 enrolled patients (median age 9 years [range 3-29]), 18 received cobimetinib tablets and 38 cobimetinib suspension. Most common diagnoses were low-grade glioma (LGG; n = 32, including n = 12 in the expansion cohort) and plexiform neurofibroma within neurofibromatosis type 1 (n = 12). Six patients (11 %) experienced dose-limiting toxicities (including five ocular toxicity events), which established a pediatric recommended Phase II dose (RP2D) of 0.8 mg/kg tablet and 1.0 mg/kg suspension. Most frequently reported treatment-related adverse events were gastrointestinal and skin disorders. Steady state mean exposure (Cmax, AUC0-24) of cobimetinib at the RP2D (1.0 mg/kg suspension) was ~ 50 % lower than in adults receiving the approved 60 mg/day dose. Overall response rate was 5.4 % (3/56; all partial responses in patients with LGG). Conclusions: The safety profile of cobimetinib in pediatrics was similar to that reported in adults. Clinical activity was observed in LGG patients with known/suspected MAPK pathway activation. Cobimetinib combination regimens may be required to improve response rates in this pediatric population.
dc.language.isoeng
dc.publisherSpringer
dc.relation.ispartofseriesTargeted Oncology;17(3)
dc.rightsAttribution-NonCommercial 4.0 International
dc.rights.urihttp://creativecommons.org/licenses/by-nc/4.0/
dc.sourceScientia
dc.subjectFarmacocinètica
dc.subjectPosologia
dc.subjectCàncer - Tractament
dc.subject.meshNeoplasms
dc.subject.mesh/drug therapy
dc.subject.meshPharmacokinetics
dc.subject.meshMaximum Tolerated Dose
dc.titleCobimetinib in Pediatric and Young Adult Patients with Relapsed or Refractory Solid Tumors (iMATRIX-cobi): A Multicenter, Phase I/II Study
dc.typeinfo:eu-repo/semantics/article
dc.identifier.doi10.1007/s11523-022-00888-9
dc.subject.decsneoplasias
dc.subject.decs/farmacoterapia
dc.subject.decsfarmacocinética
dc.subject.decsdosis máxima tolerada
dc.relation.publishversionhttps://doi.org/10.1007/s11523-022-00888-9
dc.type.versioninfo:eu-repo/semantics/publishedVersion
dc.audienceProfessionals
dc.contributor.organismesInstitut Català de la Salut
dc.contributor.authoraffiliation[Trippett T] Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, USA. [Toledano H] Department of Pediatric Hematology-Oncology, Schneider Children's Medical Center, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel. [Campbell Hewson Q] Department of Paediatric and Adolescent Oncology, The Great North Children’s Hospital, Newcastle Upon Tyne, UK. [Verschuur A] Assistance Publique-Hopitaux de Marseille, Pediatric Oncology, Timone Children’s Hospital, Marseille, France. [Langevin AM] Department of Pediatrics, UT Health San Antonio, San Antonio, TX, USA. [Aerts I] Oncology Center SIREDO, Institut Curie, PSL Research University, Paris, France. [Gallego S] Servei d’Oncologia i Hematologia Pediàtriques, Vall d’Hebron Hospital Universitari, Barcelona, Spain
dc.identifier.pmid35715627
dc.identifier.wos000812474500002
dc.rights.accessrightsinfo:eu-repo/semantics/openAccess


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