A phase II clinical study of pomalidomide (CC-4047) monotherapy for children and young adults with recurrent or progressive primary brain tumors.

person Jason R. Fangusaro Childrens' Healthcare of Atlanta and Emory University School of Medicine, Atlanta, GA info_outline Jason R. Fangusaro, Franco Locatelli, 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, Francois P. Doz, Katherine E. Warren

Authors person Jason R. Fangusaro Childrens' Healthcare of Atlanta and Emory University School of Medicine, Atlanta, GA info_outline Jason R. Fangusaro, Franco Locatelli, 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, Francois P. Doz, Katherine E. Warren Organizations Childrens' Healthcare of Atlanta and Emory University School of Medicine, Atlanta, GA, IRCCS Ospedale Bambino Gesù Children’s Hospital, Rome, Italy, University of Pavia, Pavia, Italy, Dott.ssa Oncologia Pediatrica Presso G. Gaslini, Genova, Italy, The Royal Marsden Hospital and The Institute of Cancer Research, London, United Kingdom, Istituto Nazionale Tumori, Milan, Italy, Celgene Corporation, Summit, NJ, Celgene Corporation, Uxbridge, United Kingdom, Great Ormond Street Hospital for Children, London, United Kingdom, Institut Curie, Paris, France, National Cancer Institute, National Institutes of Health, Bethesda, MD Abstract Disclosures Research Funding Pharmaceutical/Biotech Company Background: Central nervous system (CNS) tumors are the most common cause of pediatric cancer mortality and novel therapies are needed for refractory disease. Pomalidomide (pom) is an oral immunomodulatory agent with CNS penetration, anti-angiogenic, anti-inflammatory and cytotoxic activity. Methods: This Phase 2 study evaluated both safety and efficacy of pom in pediatric patients with recurrent/progressive CNS tumors. Using a Simon’s two-stage design, patients were stratified to high-grade glioma [HGG], ependymoma, medulloblastoma or diffuse intrinsic pontine glioma [DIPG] cohorts. Patients received pom 2.6 mg/m 2 for 21 days of a 28-day cycle. The primary endpoint was objective response rate (complete response [CR], partial response [PR]) or prolonged stable disease [SD] (defined as ≥ 6 cycles, or ≥ 3 for DIPG). Stage 1 required ≥ 2/9 subjects, within each cohort, to have a response or prolonged SD to move into Stage 2, and ≥ 5/20 responders or patients with prolonged SD at the end of Stage 2 for pom to be deemed effective. Results: Of 52 treated patients (median age 11.5 y/o; range 4-18), 47 were evaluable for primary endpoint. Median treatment duration was 2 cycles (range 1-16). Only the HGG cohort met protocol-defined criteria to advance to Stage 2, with one PR and one prolonged SD in Stage 1. Forty-six of 47 evaluable patients discontinued pom, due to adverse event (n = 1; pneumonia), withdrawal by parent/guardian (n = 2), death (n = 4; 3 progressive disease, 1 sepsis), or progressive disease (n = 39). Nineteen of 52 treated patients experienced ≥ 1 grade 3–4 treatment-emergent adverse event (TEAE) related to pom, neutropenia (n = 15) being the most commonly reported. Twenty-six patients died on study. All deaths were attributed to either disease progression or complications from disease. Conclusions: Single agent pomalidomide failed to meet a clinically meaningful level of efficacy in children with recurrent/progressive HGG, DIPG, medulloblastoma or ependymoma. However, it should be noted that a sustained response was observed in a child with HGG, replicating the outcome observed in one child with HGG in the Phase 1 (PBTC-043) trial. Clinical trial information: NCT03257631