Current Research Studies

PEPN2111: A Phase 1/2 Trial of CBL0137 (NSC# 825802, IND# 155843) in Patients with Relapsed or Refractory Solid Tumors including CNS Tumors and Lymphoma


What is the goal of the study?

CBL0137 is a novel small molecule inhibitor that is the first clinically developed drug in a new class of compounds termed ?curaxins.? It acts by targeting the epigenome via a complex known as FACT (Facilitates Chromatin Transcription). This leads to inhibition of a range of oncogenic pathways including inhibition of NFkB and upregulation of TP53, leading to induction of apoptosis. The FACT subunits, SSRP1 and SUPT16, are over-expressed in a range of pediatric brain tumors such as Diffuse Intrinsic Pontine Gliomas (DIPG) and solid tumors such as neuroblastoma. Moreover, FACT over-expression is highly prognostic of poor outcome in primary untreated neuroblastoma. CBL0137 has shown potent anti-tumor activity against a variety of pediatric cancer cell lines, with minimal toxicity against normal cell cultures. It has also been shown to be active in a range of pediatric solid tumor xenograft and transgenic models. Including DIPG, neuroblastoma and osteosarcoma. CBL0137 has completed Phase 1 testing in adult patients with recurrent solid tumors in both intravenous and oral formulations. The most potent anti-tumor activity in pediatric preclinical models was seen in animals treated with the intravenous formulation. We are conducting a pediatric phase 1 trial of single-agent intravenous CBL0137 given on Day 1 and Day 8 of a 21 day cycle in children with refractory or recurrent solid tumors, including CNS tumors and lymphoma. The study will use the rolling six design with the primary aim of determining the maximum-tolerated pediatric dose of CBL0137. The study will also assess the toxicity profile and determine the pharmacokinetics of CBL0137 in children with solid and CNS tumors. Once the Recommended Phase 2 Dose (RP2D) is established the study will include expansion cohorts in patients with recurrent/progressive DIPG and osteosarcoma to assess for signals of anti-tumor activity.

Who can participate in the study?

Please contact the study team listed below to learn more.

Study Team: