dc.contributor | Vall d'Hebron Barcelona Hospital Campus |
dc.contributor.author | Trippett, Tanya |
dc.contributor.author | Toledano, Helen |
dc.contributor.author | Campbell Hewson, Quentin |
dc.contributor.author | Verschuur, Arnauld |
dc.contributor.author | Langevin, Anne‑Marie |
dc.contributor.author | Gallego Melcón, Soledad |
dc.contributor.author | Aerts, Isabelle |
dc.date.accessioned | 2022-09-12T09:23:00Z |
dc.date.available | 2022-09-12T09:23:00Z |
dc.date.issued | 2022-05 |
dc.identifier.citation | Trippett 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.issn | 1776-260X |
dc.identifier.uri | https://hdl.handle.net/11351/8147 |
dc.description | Cobimetinib; Pediatrics; Refractory Solid Tumors |
dc.description.abstract | Background: 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.iso | eng |
dc.publisher | Springer |
dc.relation.ispartofseries | Targeted Oncology;17(3) |
dc.rights | Attribution-NonCommercial 4.0 International |
dc.rights.uri | http://creativecommons.org/licenses/by-nc/4.0/ |
dc.source | Scientia |
dc.subject | Farmacocinètica |
dc.subject | Posologia |
dc.subject | Càncer - Tractament |
dc.subject.mesh | Neoplasms |
dc.subject.mesh | /drug therapy |
dc.subject.mesh | Pharmacokinetics |
dc.subject.mesh | Maximum Tolerated Dose |
dc.title | Cobimetinib in Pediatric and Young Adult Patients with Relapsed or Refractory Solid Tumors (iMATRIX-cobi): A Multicenter, Phase I/II Study |
dc.type | info:eu-repo/semantics/article |
dc.identifier.doi | 10.1007/s11523-022-00888-9 |
dc.subject.decs | neoplasias |
dc.subject.decs | /farmacoterapia |
dc.subject.decs | farmacocinética |
dc.subject.decs | dosis máxima tolerada |
dc.relation.publishversion | https://doi.org/10.1007/s11523-022-00888-9 |
dc.type.version | info:eu-repo/semantics/publishedVersion |
dc.audience | Professionals |
dc.contributor.organismes | Institut 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.pmid | 35715627 |
dc.identifier.wos | 000812474500002 |
dc.rights.accessrights | info:eu-repo/semantics/openAccess |