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

ConditionsMelanoma (Skin Cancer)HER2-low Hormone Receptor Positive Breast Cancer
Trial statusRecruiting
Trial phasePhase 1, Phase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorAminex Therapeutics, Inc.

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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)

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.

Disqualifiers

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.

Trial design

Design model

Sequential

Treatments tested in this trial

  • 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)

  • DFMO

    Drug

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

  • 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

  • Capivasertib

    Drug

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

  • Pembrolizumab

    Drug

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

Treatment groups

92 Participants
are divided into 2 treatment groups
Group A: Arm 1: Breast Cancer (ER+ HER2-)Experimental treatment 4 interventions
Group B: Arm 2: MelanomaExperimental treatment 3 interventions

Trial outcomes

Primary outcomes

1

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.

Time frame
Within 24 months of last patient enrolled
2

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.

Time frame
Within 24 months of last patient enrolled
3

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.

Time frame
Within 24 months of last patient enrolled
4

Duration of Response (DOR) (Phase 2)

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

Time frame
Within 24 months of last patient enrolled

Secondary outcomes

1

Disease Control Rate (DCR)

Percentage of participants achieving CR, PR, or Stable Disease (SD) per RECIST v1.1.

Time frame
Within 24 months of last patient enrolled
2

Best Overall Response (BOR)

Best response recorded (CR, PR, SD, or PD) prior to disease progression, based on RECIST v1.1 criteria.

Time frame
Within 24 months of last patient enrolled
3

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

Proportion of patients treated with pembrolizumab (melanoma cohort) who demonstrate pseudo-progression based on iRECIST criteria.

Time frame
Within 24 months of last patient enrolled
4

Time to Response (TTR)

Time interval between start of treatment and initial objective tumor response per RECIST v1.1.

Time frame
Within 24 months of last patient enrolled

Other outcomes

1

Change in Immune-Related Gene Expression in Tumor Tissue

Change from baseline in immune-related gene expression measured by NanoString analysis in tumor tissue.

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

Tumor Tissue Concentration of AMXT-1501 and DFMO

Concentration of AMXT-1501 and DFMO measured in tumor biopsy samples.

Time frame
At Screening and end of Cycle 2 (each cycle is 28 days)
3

Tumor Polyamine Levels

Levels of polyamines measured in tumor tissue samples.

Time frame
At Screening and end of Cycle 2 (each cycle is 28 days)
4

eIF5A Hypusination Levels in Tumor Tissue

Levels of hypusinated eIF5A measured in tumor biopsy samples.

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

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Aminex Therapeutics, Inc.

Lead sponsor

Source ClinicalTrials.gov
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