Phase 2 Study of Pomalidomide (CC-4047) Monotherapy for Children and Young Adults With Recurrent or Progressive Primary Brain Tumors

Frontiers in Oncology

Katherine E. Warren¹  Jackie Quan²  Jennifer Poon²  Bouchra Benettaib²  Erin Conlin²  John Lewandowski²  Noha Biserna²  Neelum Jeste²  Mathew Simcock³  Lynley V. Marshall⁴  Maria Giuseppina Cefalo⁵  François Doz⁶  Jason Fangusaro⁷  Maria Luisa Garré⁸  Maura Massimino⁹  Darren R. Hargrave^1,10 

[1] 0National Cancer Institute, National Institutes of Health, Bethesda, MD, United States;Bristol Myers Squibb, Princeton, NJ, United States;Celgene Corporation, Uxbridge, United Kingdom;Children and Young People’s Unit, The Royal Marsden Hospital and The Institute of Cancer Research, London, United Kingdom;Department of Hematology/Oncology and Stem Cell Transplantation, IRCCS Bambino Gesù Children’s Hospital, Rome, Italy;Department of Pediatric Oncology, Institut Curie and University of Paris, Paris, France;Department of Pediatrics, Children’s Healthcare of Atlanta and Aflac Cancer Center at Emory University Medical School, Atlanta, GA, United States;Neuro-Oncology Unit, Istituto Giannina Gaslini, Genoa, Italy;Pediatric Oncology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy;Pediatric Oncology Unit, UCL Great Ormond Street Hospital for Children, London, United Kingdom;

关键词: diffuse intrinsic pontine glioma;    ependymoma;    high-grade glioma;    medulloblastoma;    pomalidomide;    progressive or recurrent disease;   

DOI  :  10.3389/fonc.2021.660892

来源: DOAJ

【 摘 要 】

IntroductionTreatment of recurrent primary pediatric brain tumors remains a major challenge, with most children succumbing to their disease. We conducted a prospective phase 2 study investigating the safety and efficacy of pomalidomide (POM) in children and young adults with recurrent and progressive primary brain tumors.MethodsPatients with recurrent and progressive high-grade glioma (HGG), diffuse intrinsic pontine glioma (DIPG), ependymoma, or medulloblastoma received POM 2.6 mg/m2/day (the recommended phase 2 dose [RP2D]) on days 1-21 of a 28-day cycle. A Simon’s Optimal 2-stage design was used to determine efficacy. Primary endpoints included objective response (OR) and long-term stable disease (LTSD) rates. Secondary endpoints included duration of response, progression-free survival (PFS), overall survival (OS), and safety.Results46 patients were evaluable for response (HGG, n = 19; DIPG, ependymoma, and medulloblastoma, n = 9 each). Two patients with HGG achieved OR or LTSD (10.5% [95% CI, 1.3%-33.1%]; 1 partial response and 1 LTSD) and 1 patient with ependymoma had LTSD (11.1% [95% CI, 0.3%-48.2%]). There were no ORs or LTSD in the DIPG or medulloblastoma cohorts. The median PFS for patients with HGG, DIPG, ependymoma, and medulloblastoma was 7.86, 11.29, 8.43, and 8.43 weeks, respectively. Median OS was 5.06, 3.78, 12.02, and 11.60 months, respectively. Neutropenia was the most common grade 3/4 adverse event.ConclusionsTreatment with POM monotherapy did not meet the primary measure of success in any cohort. Future studies are needed to evaluate if POM would show efficacy in tumors with specific molecular signatures or in combination with other anticancer agents.Clinical Trial RegistrationClinicalTrials.gov, identifier NCT03257631; EudraCT, identifier 2016-002903-25.

【 授权许可】

Unknown