AMXT 1501 Dicaprate

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Also known as:

AMX 513 dicaprate

Cancer types include:

brain tumor breast cancer melanoma sarcoma

TrialFetch AI Analysis

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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)

Active trials using AMXT 1501 Dicaprate

Found 3 active trials using this drug:

A Phase 1b/2 Trial Investigating the Safety and Efficacy of Oral AMXT 1501 and Oral DFMO in Combination With Standard of Care in Patients With Advanced Solid Tumors Who Progressed After Prior Therapies

Sponsor: Aminex Therapeutics, Inc. (industry) Phase: 1/2 Start date: Dec. 17, 2025

TrialFetch AI summary: For adults with ECOG 0–1 and measurable unresectable/metastatic disease, this study enrolls either ER+/HER2− breast cancer with actionable PIK3CA/AKT1/PTEN alterations after progression on ≥2 endocrine-based regimens (candidate for fulvestrant + capivasertib) or cutaneous melanoma progressing after prior immune checkpoint inhibitor therapy (and after/intolerant to BRAF/MEK inhibitors if BRAF V600–mutant). Patients receive dual polyamine blockade with oral AMXT 1501 (polyamine transport inhibitor) plus oral DFMO/eflornithine (irreversible ornithine decarboxylase inhibitor) added to standard therapy—fulvestrant + capivasertib in breast cancer or pembrolizumab in melanoma.

ClinicalTrials.gov ID: NCT07287917

A Multicenter, Phase II Trial of Relatlimab, Nivolumab, and Ipilimumab in Patients With Asymptomatic and Symptomatic Melanoma Brain Metastases

Sponsor: Stanford University (other) Phase: 2 Start date: Aug. 6, 2025

TrialFetch AI summary: Adults with non-uveal melanoma and measurable untreated brain metastases (including asymptomatic ECOG 0–1 and symptomatic ECOG 0–2 with limited steroids) receive triple checkpoint blockade: nivolumab (PD-1 inhibitor) plus relatlimab (LAG-3 inhibitor) combined with ipilimumab (CTLA-4 inhibitor). Prior adjuvant/neoadjuvant PD-1/CTLA-4/LAG-3 allowed if >6 months; excludes leptomeningeal disease, prior whole-brain RT, active autoimmune disease requiring systemic therapy, and significant cardiac comorbidity.

ClinicalTrials.gov ID: NCT06712927

A Dose Escalation Study Using Eflornithine (DFMO) and AMXT 1501 Followed by a Randomized Controlled Trial of DFMO With or Without AMXT 1501 for Neuroblastoma, CNS Tumors, and Sarcomas

Sponsor: Milton S. Hershey Medical Center (other) Phase: 1/2 Start date: June 18, 2024

TrialFetch AI summary: Pediatric, adolescent, and young adult patients with relapsed/refractory neuroblastoma (randomized to DFMO with or without AMXT 1501) and single-arm cohorts for relapsed/refractory ETMR/ATRT, newly diagnosed DIPG post-RT, and relapsed/refractory Ewing sarcoma or osteosarcoma receive oral eflornithine (DFMO) with AMXT 1501. AMXT 1501 inhibits polyamine transport and DFMO irreversibly inhibits ornithine decarboxylase, aiming to block both polyamine uptake and synthesis.

ClinicalTrials.gov ID: NCT06465199