Phase 1, open-label, multi-center trial of RPT1G in patients with relapsed/refractory acute myeloid leukemia and higher-risk myelodysplastic syndromes/neoplasms
Abstract
TPS6601
Background:
Nicotinamide phosphoribosyltransferase (NAMPT), the rate limiting enzyme in the NAD salvage pathway, regulates cellular energy metabolism and is overexpressed in blood cancers. Because cancer cells depend on elevated NAD-flux, they are highly sensitive to NAMPT inhibition. Since normal cells also require NAD for survival, prior clinical trials of complete NAMPT inhibitors lead to dose-limiting toxicities. We developed RPT1G, a novel hyperbolic inhibitor with an improved therapeutic window that enables therapeutically effective NAD depletion in malignant cells while sparing normal tissues (Crimmins, ASH 2023). A first-in-human, Phase 1, randomized, double-blind, placebo-controlled, SAD and MAD study in healthy volunteers of RPT1G showed that oral administration of RPT1G is safe and well-tolerated with a favorable pharmacokinetics (PK) profile. Target engagement results showed that RPT1G inhibits NAMPT at doses predicted to be therapeutically relevant.
Methods:
RPT1G is being investigated in a Phase 1, multi-center, open-label clinical trial (NCT07107126) for treatment of Relapsed/Refractory Acute Myeloid Leukemia (R/R AML) and Higher-Risk Myelodysplastic Syndromes/Neoplasms (HR-MDS). It is the first NAMPT hyperbolic inhibitor to be studied for the treatment of R/R-AML and HR-MDS patients. With a standard 3+3 design, this study explores escalating oral doses of RPT1G, given twice daily in 28-day cycles. Other dosing schedules will be studied based on…
How strong is the evidence?
Evidence Hub reads this as a randomized trial, done in people. Its evidence level is 2 of 5 (High · randomized trial). Randomized trials of a reasonable size are the strongest single-study design.
Read the paper
Related studies
- Chaos and quantum thermalization
- The Dalton quantum chemistry program system
- Cord Blood Leptin and Adiponectin as Predictors of Adiposity in Children at 3 Years of Age: A Prospective Cohort Study
- Quantitative metabolomics by H-NMR and LC-MS/MS confirms altered metabolic pathways in diabetes
- Stable adiabatic quantum batteries
- A novel self-lipid antigen targets human T cells against CD1c(+) leukemias
Go deeper in Evidence Hub
Evidence Hub adds a study data sheet (design, sample size, evidence level, key numbers), an AI summary and a chat grounded in the paper's text.