PEPN2011, A Phase 1/2 Study of Tegavivint (IND#156033, NSC#826393) in Children, Adolescents, and Young Adults with Recurrent or Refractory Solid Tumors, Including Lymphomas and Desmoid Tumors
PEPN2011
What is the goal of the study?
Tegavivint is a novel small molecule inhibitor of Wnt-ß-catenin signaling, which is involved in a myriad of cellular processes including proliferation, differentiation, and oncogenesis. Aberrant Wnt signaling has been identified as a key mechanism of cancer biology, resulting in uncontrolled transcription of Wnt target genes, several of which are oncogenes. Tegavivint binds to transducin ß-like protein 1 (TBL1) preventing the binding of TBL1 to ß-catenin, which results in nuclear degradation of ß-catenin and, therefore, prevents transcription of Wnt target genes. Importantly, tegavivint specifically inhibits nuclear ß-catenin and oncogenic gene transcription without affecting upstream membrane-bound or cytoplasmic ß-catenin, which have other important, non-oncogenic cellular functions. Pre-clinical in vivo studies demonstrate anti-tumor activity in a variety of pediatric solid tumors, including osteosarcoma, Ewing sarcoma, and lymphoma. A phase 1/2 study of tegavivint in adults with progressive desmoid tumors has shown promising results and has been well-tolerated with no dose limiting toxicities. We are conducting a phase 1/2 trial of single-agent tegavivint in children, adolescents, and young adults with recurrent or refractory solid tumors, including lymphomas and desmoid tumors. Part A, dose escalation, will be conducting using the rolling six design. The aims of Part A are to determine the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) of tegavivint, as well as to describe the toxicities and pharmacokinetics of tegavivint administered as an IV infusion over 4 hours, once weekly for 3 weeks, followed by 1 week rest, in a 28-day cycle. Once Part A is complete, Part B, Phase 2 expansion cohorts, will open for Ewing sarcoma, desmoid tumors, osteosarcoma, liver tumors, Wilms tumor, and tumors with Wnt pathway aberrations. The 10+10 Simon?s optimal two stage design will be used for parts B1 (Ewing) and B2 (Desmoid). Parts B4 (Liver), B5 (Wilms), and B6 (Wnt pathway aberrations) are non-statistical cohorts; however, these cohorts will follow the 5+2 minimax design if sufficient enrollment occurs. Part B3 (Osteosarcoma) will follow the 14+11 Simon?s optimal two stage design with response assessed at the 4-month time point. The primary aim of Part B is to preliminarily define the antitumor activity of tegavivint in pediatric patients with these solid tumors.
Who can participate in the study?
Please contact the study team listed below to learn more.