Study of AMXT 1501 and DFMO in Combination With Standard Therapies in Advanced Solid Tumors

NCT07287917 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: AMXT1501-103
• Study Type: interventional
• Target: 92
• Locations: 1 country
• Sites: 12

Brief Summary

This study will evaluate the safety, tolerability, and preliminary effectiveness of AMXT 1501 and DFMO when combined with standard treatments for advanced solid tumors. The trial includes two groups:

• Cohort 1: Patients with ER+ / HER2- breast cancer receiving fulvestrant and capivasertib
• Cohort 2: Patients with unresectable or metastatic cutaneous melanoma receiving pembrolizumab The Phase 1b portion will find the recommended Phase 2 dose (RP2D). The Phase 2 portion will further evaluate clinical activity at the RP2D using response criteria for solid tumors (RECIST 1.1). The study will also evaluate pharmacokinetics, pharmacodynamics, disease control, and overall safety.

Conditions

Melanoma (Skin Cancer); HER2-low Hormone Receptor Positive Breast Cancer

Keywords

breast cancer; melanoma; AMXT 1501; DFMO; polyamine inhibitor; advanced solid tumor; combination therapy; polyamine

Outcome Measures

Primary Outcomes (4)

• Incidence of Dose-Limiting Toxicities (DLTs)

  Number of participants experiencing dose-limiting toxicities as defined in the protocol, including hematologic and non-hematologic toxicities, treatment-related dosing delays, missed doses, or any toxicity leading to discontinuation during the DLT evaluation period.

  Within 24 months of last patient enrolled

• Incidence, Frequency, and Severity of Adverse Events (AEs)

  Assessment of all treatment-emergent adverse events graded using CTCAE v5.0, including clinical labs, vital signs, ECGs, cardiac biomarkers, and physical examinations, to evaluate the safety and tolerability of AMXT 1501 + DFMO with SOC.

  Within 24 months of last patient enrolled

• Objective Response Rate (ORR) (Phase 2)

  Proportion of participants achieving a confirmed Complete Response (CR) or Partial Response (PR) per RECIST v1.1 as assessed by the investigator.

  Within 24 months of last patient enrolled

• Duration of Response (DOR) (Phase 2)

  Duration for which a patient maintains a confirmed objective response per RECIST v1.1.

  Within 24 months of last patient enrolled

Secondary Outcomes (9)

• Disease Control Rate (DCR)

  Within 24 months of last patient enrolled

• Best Overall Response (BOR)

  Within 24 months of last patient enrolled

• Percentage of Patients With Pseudo-Progression (iRECIST) (Melanoma Cohort)

  Within 24 months of last patient enrolled

• Time to Response (TTR)

  Within 24 months of last patient enrolled

• Progression-Free Survival (PFS)

  Within 24 months of last patient enrolled

Other Outcomes (4)

• Change in Immune-Related Gene Expression in Tumor Tissue

  From baseline (Screening) to end of Cycle 2 (each cycle is 28 days)

• Tumor Tissue Concentration of AMXT-1501 and DFMO

  At Screening and end of Cycle 2 (each cycle is 28 days)

• Tumor Polyamine Levels

  At Screening and end of Cycle 2 (each cycle is 28 days)

Study Arms (2)

Arm 1: Breast Cancer (ER+ HER2-)

EXPERIMENTAL

Arm 1: Breast Cancer Cohort (Cohort 1: ER+ / HER2-) AMXT 1501 oral DFMO oral Fulvestrant IM Capivasertib PO

Drug: AMXT 1501 Dicaprate; Drug: DFMO; Drug: Fulvestrant; Drug: Capivasertib

Arm 2: Melanoma

EXPERIMENTAL

Arm 2: Melanoma Cohort (Cohort 2: Melanoma) AMXT 1501 oral DFMO oral Pembrolizumab IV

Drug: AMXT 1501 Dicaprate; Drug: DFMO; Drug: Pembrolizumab

Interventions

AMXT 1501 Dicaprate DRUG

Formulation: Enteric-coated oral tablet (100 mg base) Dose: Body-surface-area-adjusted; starting dose = 300 mg PO BID; may escalate per 3 + 3 design Administration: By mouth on an empty stomach (AM and PM doses)

Also known as: AMXT 1501

Arm 1: Breast Cancer (ER+ HER2-); Arm 2: Melanoma

DFMO DRUG

Formulation: 500 mg gel capsule Dose: 500 mg PO once or twice daily, per cohort dose level

Also known as: Difluoromethylornithine

Arm 1: Breast Cancer (ER+ HER2-); Arm 2: Melanoma

Fulvestrant DRUG

Dose: 500 mg IM injection on Day 2 and Day 15 of Cycle 1, then Day 2 of each subsequent 28-day cycle

Arm 1: Breast Cancer (ER+ HER2-)

Capivasertib DRUG

Dose: 400 mg PO BID for 4 days on / 3 days off each week (28-day cycle)

Arm 1: Breast Cancer (ER+ HER2-)

Pembrolizumab DRUG

200 mg IV infusion every 3 weeks (Q3W) for up to 12 months

Also known as: Keytruda®

Arm 2: Melanoma

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Understand and sign the informed consent form (ICF) and be willing to comply with all study procedures before any study specific procedures are conducted.
• ≥18 years old at the time of signing the informed consent.
• Diagnosed with unresectable, locally advanced, or metastatic solid tumors including ER+ HER2- breast cancer (Cohort 1) or melanoma (Cohort 2)
• a.Underlying malignant disease must be histologically or cytologically documented b.For breast cancer patients: locally advanced or metastatic breast cancer with one or more actionable PIK3CA/AKT1/PTEN-alterations following progression on at least 2 endocrine-based regimens in the metastatic setting or recurrence on or within 12 months of completing adjuvant therapy. Patients who are candidates to start therapy with capivasertib are eligible for enrollment. Patients previously treated with PIK3CA inhibitors will be allowed into the study. Premenopausal patients with ER+ HER2-breast cancer may be enrolled and should be maintained on an agent for ovarian suppression (i.e., luteinizing hormone-releasing hormone \[LHRH\] agonist) as part of SOC.
• c.For melanoma patients: patients with unresectable metastatic cutaneous melanoma that progressed on any prior immune checkpoint inhibitor and, if BRAF600 mutant positive, a BRAF or mitogen-activated protein kinase (MEK) inhibitor or both as shown below: i.Patient have to have resolution of all immune checkpoint inhibitor-related adverse events to Grade 0-1 and prednisone ≤10 mg/day for at least 2 weeks. Histologically or cytologically confirmed diagnosis of unresectable Stage III or metastatic melanoma not amenable to local therapy.
• ii.Patients must have progressed or shown intolerance to any prior immune checkpoint inhibitors.
• iii.Patients with BRAF gene mutant melanoma must have had a prior treatment regimen (progressed or shown intolerance) that included vemurafenib, dabrafenib, or an approved BRAF gene and or MEK protein inhibitor. However, patients who may continue to be candidates for second line immune check point inhibitors can be enrolled prior to initiation for BRAF gene or MEK inhibitors.
• iv.Patients with incurable malignancies may be enrolled regardless of the number of prior treatment lines, as long as in the opinion of the Investigator, the patient would be unlikely to tolerate or derive clinically meaningful benefit from other available treatment options (FDA Guidance for Industry: Cancer Clinical Trial Eligibility Criteria: Available Therapy in Non-Curative Settings. July 2022).
• d.Has evaluable or measurable disease by tumor Response Evaluable Criteria in Solid Tumors version 1.1 (RECIST 1.1) at the time of enrollment. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
• e.Patients with brain previously treated stable brain metastases may participate provided they are radiologically stable, i.e., without evidence of progression for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study treatment.
• Patients must be willing to undergo a fresh tumor biopsy at Screening and during treatment if safe and clinically feasible. An archival sample is allowed if obtained within 1 year prior to the first dose of study drug. However, lack of tumor biopsy by itself will not preclude patients from enrollment.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 at Screening or Day 1.
• Life expectancy of at least 12 weeks.
• Adequate organ function defined as:
• a.Absolute neutrophil count (ANC) ≥1.5×109/L without granulocyte colony-stimulating factor (G-CSF) support within 7 days preceding the laboratory assessment b.Platelet ≥100×109/L, without transfusion within 7 days preceding the laboratory assessment c.Hemoglobin ≥9 g/dL, without transfusion support within 7 days preceding the laboratory assessment d.Activated partial thromboplastin time/partial thromboplastin time (aPTT/PTT) ≤1.5×ULN e.Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5×ULN (if liver metastases are present, then ≤5×ULN is allowed) f.Total serum bilirubin ≤1.5×ULN, except for patients with known Gilbert's Syndrome in whom ≤3×ULN is permitted. Confirmation of Gilbert's diagnosis requires elevated unconjugated (indirect) bilirubin values; normal complete blood count in previous 12 months, blood smear, and reticulocyte count; normal aminotransferases and alkaline phosphatase in previous 12 months g.The patient is clinically euthyroid (whether treated or untreated) h.Renal: Serum creatinine ≤1.5×ULN or creatinine clearance ≥60 mL/min/1.73 m2 for patients with serum creatinine levels \>1.5×ULN i.Any Grade 3 or higher laboratory abnormalities should be discussed and approved by the Sponsor Medical Monitor or designee prior to enrollment (even if not considered clinically significant)

You may not qualify if:

• Patients with melanoma only:
• i. Radiation therapy, or biological cancer therapy within 4 weeks prior to the first dose of study drug, or not recovered from the AEs due to cancer therapies administered more than 4 weeks earlier ii.Expected to require any other form of systemic or localized antineoplastic therapy while on study.
• iii.Chronic systemic steroid therapy within 2 weeks before the planned date of the first dose of randomized treatment or on any other form of immunosuppressive medication.
• Intolerant to any component of combination or standard of care therapies.
• History or presence of clinically relevant central nervous system (CNS) pathology such as epilepsy, seizure, paresis, aphasia, stroke, severe brain injury, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, or psychosis. Patient has known active CNS metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable, i.e., without evidence of progression for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study treatment.
• Active inflammatory neurological disorders (e.g., Guillain-Barre Syndrome, amyotrophic lateral sclerosis, multiple sclerosis).
• Treatment with radiation therapy, surgery, chemotherapy, or immunotherapy within 4 weeks prior to study entry (6 weeks for nitrosoureas or Mitomycin C). No prior use of Adriamycin is allowed. Limited prior palliative radiation may be permissible no less than 2 weeks prior to C1D1 with approval from the Sponsor Medical Monitor or designee.
• Targeted small molecule therapy within 7 days prior to initiation of trial therapy. Chemotherapy within 14 days prior to initiation of trial therapy.
• Active autoimmune disease (e.g., lupus, rheumatoid arthritis, Sjogren's syndrome) requiring systemic treatment (i.e., disease modifying agents, corticosteroids, or immunosuppressive drugs) in the past 2 years. Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
• History of or presence of clinically significant cardiovascular disease, e.g.,
• a. Inadequately controlled or uncontrolled hypertension (defined as systolic blood pressure \>150 mmHg and/or diastolic blood pressure \>100 mmHg on antihypertensive medications.) b. Atherosclerotic cardiovascular disease including history of myocardial infarction, unstable angina, angina, coronary artery disease, cerebrovascular accident (CVA) or transient ischemic attack (TIA). History of coronary revascularization including coronary artery bypass graft (CABG), percutaneous coronary intervention (PCI) or stent placement is excluded. c. Elevated Troponin I or BNP (or NT-proBNP) blood levels above the upper limit of normal at screening or baseline on C1D1.
• d. Heart failure or abnormal left ventricular ejection fraction (e.g., EF \<50%).
• e. Atrial or ventricular arrhythmias, including atrial fibrillation, ventricular tachycardia. Patients with pacemakers or ICDs (implantable cardioverter defibrillators) are excluded.
• f. Known cardiac involvement of a systemic disease (e.g., as in SLE, rheumatoid arthritis, psoriatic arthritis, systemic sclerosis
• History or presence of ECG abnormalities, e.g.,

Sponsors & Collaborators

• Aminex Therapeutics, Inc.: lead

Study Sites (12)

START Los Angeles

Los Angeles, California, 90025, United States

RECRUITING

Skin Cancer Institute

Englewood, Colorado, 80113, United States

RECRUITING

Wayne State University - Barbara Ann Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

RECRUITING

START Cancer Research New York-Long Island

Lake Success, New York, 11042, United States

RECRUITING

University of Cincinnati Medical Center

Cincinnati, Ohio, 45219, United States

RECRUITING

Vanderbilt-Ingram Cancer Institute

Nashville, Tennessee, 37232, United States

RECRUITING

University of Texas-MD Anderson

Houston, Texas, 77030, United States

RECRUITING

Lumi Research

Houston, Texas, 77090, United States

RECRUITING

Laguna Clinical Research Associates

Laredo, Texas, 78041, United States

RECRUITING

START Mountain Region

West Valley City, Utah, 84119, United States

RECRUITING

Virginia Cancer Specialists-Fairfax

Fairfax, Virginia, 22031, United States

RECRUITING

University of Wisconsin-Madison Carbone Cancer Center

Madison, Wisconsin, 53706, United States

RECRUITING

MeSH Terms

Conditions

Melanoma; Breast Neoplasms

Interventions

Eflornithine; Fulvestrant; capivasertib; pembrolizumab

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases; Breast Diseases

Intervention Hierarchy (Ancestors)

Ornithine; Amino Acids, Basic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Diamino; Estradiol; Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Study Officials

• Deyaa Adib, MD

  Aminex Therapeutics, Inc.

  STUDY DIRECTOR

Central Study Contacts

Mark Burns, PhD

CONTACT

425-524-1615; mburns@aminextx.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 24, 2025
• First Posted: December 17, 2025
• Study Start: January 26, 2026
• Primary Completion (Estimated): February 28, 2028
• Study Completion (Estimated): December 29, 2028
• Last Updated: May 5, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (12)