AMXT 1501 Dicaprate

Overview

AMXT 1501 dicaprate (also known as AMX 513 dicaprate or AMXT-1501) is an oral small-molecule polyamine transport inhibitor being developed primarily in combination with difluoromethylornithine (DFMO/eflornithine), an irreversible inhibitor of ornithine decarboxylase (ODC). A first-in-human, multi-part phase 1 study in advanced solid tumors has been completed and published in 2025. Pediatric development is planned in neuroblastoma, for which the combination received FDA Orphan Drug Designation in October 2025. (pubmed.ncbi.nlm.nih.gov)

Mechanism of action

• Rationale: Many tumors upregulate polyamine metabolism, which promotes tumor growth and immunosuppression. DFMO reduces de novo polyamine synthesis by inhibiting ODC; tumor cells can compensate by increasing uptake of extracellular polyamines, motivating dual blockade. (pubmed.ncbi.nlm.nih.gov)
• AMXT 1501: Inhibits polyamine transport into cancer cells, thereby complementing DFMO to suppress both synthesis and uptake. Preclinical studies show synergy of AMXT 1501 + DFMO across models including neuroblastoma and diffuse intrinsic pontine glioma (DIPG). (pubmed.ncbi.nlm.nih.gov)
• Molecular targets: Emerging evidence implicates transporter proteins such as SLC3A2 and ATP13A3 in polyamine uptake; AMXT 1501 inhibits uptake mediated by these transporters in preclinical systems. (pubmed.ncbi.nlm.nih.gov)

Efficacy

Phase 1 (NCT03536728) in heavily pretreated patients with unresectable, locally advanced, or metastatic solid tumors (n=56) evaluated AMXT 1501 alone and in combination with DFMO, then established the combination dose and included an expansion cohort. Confirmed responses were observed in 2 patients; 16 had stable disease, yielding an overall response rate of 6% and a clinical benefit rate of 49%. The recommended phase 2 dose (RP2D) was AMXT 1501 600 mg twice daily plus DFMO 500 mg. (pubmed.ncbi.nlm.nih.gov)

Additional ongoing/early clinical work includes a phase 0 pharmacodynamic study assessing DFMO with or without AMXT 1501 in high-grade glioma using intracranial microdialysis to measure tumor extracellular metabolites; results are exploratory. (mayo.edu)

In pediatrics, a multicenter trial of eflornithine plus AMXT 1501 in neuroblastoma and related tumors is planned (NCT06465199; not yet recruiting as of September 10, 2025). (onclive.com)

Safety

In the phase 1 study (n=56), the most common treatment-emergent adverse events were gastrointestinal: diarrhea (39.3%), nausea (37.5%), and vomiting (33.9%). No grade 4–5 treatment-emergent adverse events and no treatment-emergent deaths were reported. Overall, the combination was considered tolerable with preliminary antitumor activity. (pubmed.ncbi.nlm.nih.gov)

Further reading

• ESMO Open phase 1 publication (2025): design, RP2D, and safety/efficacy outcomes. (pubmed.ncbi.nlm.nih.gov)
• Preclinical synergy and rationale in neuroblastoma. (pubmed.ncbi.nlm.nih.gov)
• Preclinical dual-targeting strategy and transporter upregulation in DIPG. (pubmed.ncbi.nlm.nih.gov)
• Mechanistic evidence that ATP13A3 mediates DFMO-induced polyamine uptake and is inhibited by AMXT 1501. (pubmed.ncbi.nlm.nih.gov)
• FDA Orphan Drug Designation in neuroblastoma and planned pediatric study details. (onclive.com)

Notes: As of November 11, 2025, published human efficacy data consist of the single-arm phase 1 trial in mixed solid tumors; randomized efficacy data have not yet been reported. (pubmed.ncbi.nlm.nih.gov)

Last updated: Nov 2025