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

Jason Fangusaro; Maria Giuseppina Cefalo; Maria Luisa Garré; Lynley V Marshall; Maura Massimino; Bouchra Benettaib; Noha Biserna; Jennifer Poon; Jackie Quan; Erin Conlin; John Lewandowski; Mathew Simcock; Neelum Jeste; Darren R Hargrave; François Doz; Katherine E Warren

doi:10.3389/fonc.2021.660892

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

Front Oncol. 2021 Jun 8:11:660892. doi: 10.3389/fonc.2021.660892. eCollection 2021.

Authors

Jason Fangusaro¹, Maria Giuseppina Cefalo², Maria Luisa Garré³, Lynley V Marshall⁴, Maura Massimino⁵, Bouchra Benettaib⁶, Noha Biserna⁶, Jennifer Poon⁶, Jackie Quan⁶, Erin Conlin⁶, John Lewandowski⁶, Mathew Simcock⁷, Neelum Jeste⁶, Darren R Hargrave⁸, François Doz⁹, Katherine E Warren¹⁰

Affiliations

¹ Department of Pediatrics, Children's Healthcare of Atlanta and Aflac Cancer Center at Emory University Medical School, Atlanta, GA, United States.
² Department of Hematology/Oncology and Stem Cell Transplantation, IRCCS Bambino Gesù Children's Hospital, Rome, Italy.
³ Neuro-Oncology Unit, Istituto Giannina Gaslini, Genoa, Italy.
⁴ Children and Young People's Unit, The Royal Marsden Hospital and The Institute of Cancer Research, London, United Kingdom.
⁵ Pediatric Oncology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
⁶ Bristol Myers Squibb, Princeton, NJ, United States.
⁷ Celgene Corporation, Uxbridge, United Kingdom.
⁸ Pediatric Oncology Unit, UCL Great Ormond Street Hospital for Children, London, United Kingdom.
⁹ Department of Pediatric Oncology, Institut Curie and University of Paris, Paris, France.
¹⁰ National Cancer Institute, National Institutes of Health, Bethesda, MD, United States.

Abstract

Introduction: Treatment 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.

Methods: Patients 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.

Results: 46 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.

Conclusions: Treatment 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 registration: ClinicalTrials.gov, identifier NCT03257631; EudraCT, identifier 2016-002903-25.

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

Associated data

ClinicalTrials.gov/NCT03257631