Phase 1 Evaluation of the Safety and Pharmacokinetics of First-in-Class N-Myristoylation Inhibitor PCLX-001 in Patients with Relapsed/ Refractory Acute Myeloid
Abstract
This is Phase 1 Study of Oral PCLX-001 in Relapsed/Refractory (R/R) Acute Myeloid Leukemia (AML) PCLX-001 is an oral small molecule N-myristoyltransferase (NMT) inhibitor that potently and selectively inhibits the growth of human Acute Myeloid Leukemia (AML)cells in vitro and in vivo models of human AM. Myristoylation, the N-terminal modification of proteins with the fatty acid myristate, is critical for targeting some proteins to the cell membrane and intracellular signaling. There is evidence of selective toxicity to malignant stem cell populations. An ongoing Phase 1 dose escalation study in lymphoma and solid tumor patients shows pharmacokinetic (PK) suitable for once daily oral dosing, achieving plasma concentrations continuously exceeding levels required to inhibit cultured AML cells. No dose limiting toxicities (DLT) have been identified in dose escalation up to 100 mg, and preliminary evidence of anti-cancer efficacy has beenobserved. PCXL-001 warrants further evaluation in adult AML. adult AML.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2023
- Accession Number
- AD1227936
Entities
People
- Naveen Pemmaraju
Organizations
- The University of Texas MD Anderson Cancer Center