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, 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

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.

Conflict of interest statement

BB, NB, JP, JQ, EC, JL and NJ were employed by Bristol Myers Squibb. MS is employed by and has stock ownership with Celegne. JF: Related to the work: Celgene (a Bristol-Myers Squibb Company) (advisory board). LM: Honoraria/consulting/advisory boards for Bristol-Myers Squibb, Bayer, Eisai, Tesaro. MM: Bristol-Myers Squibb (advisory boards and travel expenses), Roche (advisory board), Novartis (advisory board), Oncoscience (advisory board). BB, NB, JP, JQ, EC, JL and NJ: Employment and stock ownership with Bristol-Myers Squibb Company. DH: Related to the work: Celgene (a Bristol-Myers Squibb Company) (advisory board). Not related to the work: Consulting, AstraZeneca, Bayer, Boehringer Ingelheim, Novartis, Roche/Genentech; research funding, AstraZeneca; expert testimony, AstraZeneca; travel, Boehringer Ingelheim, Novartis, Roche/Genentech; other, AbbVie, Bristol-Myers Squibb, and Novartis. FD: Related to the work: Celgene (a Bristol-Myers Squibb Company) (advisory board). Not related to the work: Bayer (advisory boards and travel expenses), Bristol-Myers Squibb (advisory boards and travel expenses), Roche (advisory board and travel expenses), Loxo Oncology (advisory board), Novartis (advisory board), Tesaro (advisory board), Servier (advisory boards and consulting). KW: Related to the work: Celgene (a Bristol-Myers Squibb Company) (advisory board). Not related to the work: Celgene (a Bristol-Myers Squibb Company) (clinical trial sponsorship). The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The authors declare that this study received funding from Bristol Myers Squibb. The sponsor was involved in the study design, collection, analysis, interpretation of data, and funded the writing of this article.

Copyright © 2021 Fangusaro, Cefalo, Garré, Marshall, Massimino, Benettaib, Biserna, Poon, Quan, Conlin, Lewandowski, Simcock, Jeste, Hargrave, Doz and Warren.

Figures

Figure 1
Figure 1
Patient Disposition by Tumor Type (safety population).

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