Oral AMXT 1501 Dicaprate in Combination With DFMO

NCT03536728 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: AMXT1501-101A
• Study Type: interventional
• Target: 56
• Locations: 1 country
• Sites: 4

Brief Summary

A Phase 1 study will be conducted to establish safety and dose level of AMXT 1501 dicaprate alone, and in combination with DFMO, in cancer patients.

Conditions

Cancer; Solid Tumor; Solid Carcinoma; Advanced Cancer

Keywords

DFMO; AMXT 1501

Outcome Measures

Primary Outcomes (2)

• Determine DLTs and RP2Ds in AMXT 1501 in combination with DFMO

  To evaluate dose-limiting toxicities (DLTs) of AMXT 1501 in combination with DFMO, in patients with advanced cancer and to establish a recommended Phase 2 dose (RP2D)

  2 years

• Determine safety and tolerability of AMXT1501 in combination with DFMO

  To evaluate the safety and tolerability of AMXT1501 and DFMO combination

  2 years

Secondary Outcomes (5)

• Determine the PK using AUC of AMXT 1501 and in combination with DFMO

  6 months

• Determine the PK using Cmax of AMXT 1501 and in combination with DFMO

  6 months

• Characterize investigator defined response Overall Response Rate (ORR) using RECIST v1.1

  6 months

• Characterize investigator defined Duration of Response (DOR)

  6 months

• Characterize AMXT1501 in combination with DFMO on the expression of immune related gene signatures

  1 year

Other Outcomes (1)

• Evaluate AMXT1501 in combination with DFMO on PD biomarker by evaluating the level/concentration of polyamine uptake in the blood.

  6 months

Study Arms (3)

Part 1

EXPERIMENTAL

Dose escalation of AMXT1501 with a fixed low dose of DFMO will follow a 3 + 3 dose escalation design. The AMXT 1501 starting dose administered in the first cohort will be 80 mg (2 capsules); each capsule contains 40 mg of active drug. The dose will be given orally, once daily, fasted state alone for 14 days, and starting on Day 15 AMXT 1501 80 mg given in combination with fixed low-dose oral DFMO at 250mg 2x per day (BID), for an additional 14 days; for a total 28 days of treatment per cycle. Cycle 2 includes AMXT1501 + DFMO that will be administered for 28 days. The patient can be treated for additional 28 day treatment cycles as deemed appropriate by their study investigator. Dose escalation of AMXT1501 alone will increase per Part 1 cohort.

Drug: AMXT1501; Drug: DFMO

Part 2

EXPERIMENTAL

Dose escalation of DFMO with the Part 1 AMXT1501 RP2D fixed dose will follow a 3 + 3 dose escalation design. The AMXT 1501 starting dose administered in the first cohort will be one level below the AMXT 1501 Part 1 RP2D with 500 mg DFMO BID. The morning dose will be given orally of both AMXT1501 and DFMO, in a fasted state. The evening dose of DFMO alone will be given prior to bed-time for 28 days per cycle. The patient can be treated for additional 28 day treatment cycles as deemed appropriate by their study investigator. Dose escalation of DFMO alone will increase per Part 2 cohort.

Drug: AMXT1501; Drug: DFMO

Expansion

EXPERIMENTAL

The expansion cohort will include up to 14 evaluable patients at a proposed RP2D level of AMXT1501 and DFMO defined by Part 2 to further characterize safety at proposed RP2D dose level with repeat dosing, and characterize early anti-tumor activity.

Drug: AMXT1501; Drug: DFMO

Interventions

AMXT1501 DRUG

AMXT 1501 dicaprate is D-lys(palmitoyl)-spermine dicaprate salt in 40 mg or 200 mg (free base content) enterically-coated capsules

Expansion; Part 1; Part 2

DFMO DRUG

DFMO is DL-2-(difluoromethyl) ornithine monohydrochloride monohydrate 250 mg in hard gelatin capsules

Also known as: difluoromethyl ornithine monohydrochloride

Expansion; Part 1; Part 2

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Individuals eligible to participate in this study must meet all the following criteria:
• Understand and sign written Institutional Review Board (IRB)-approved informed consent form and be willing to comply with all study procedures.
• Participants must be ≥18 years of age.
• Patient is able to take oral medications.
• Histologically or cytologically documented disease, with the exception of patients with cancers that are not biopsied but where there is radiological evidence of documented disease.
• Unresectable, locally advanced, or metastatic solid tumor for which no standard therapy is recognized or for which standard therapy has failed.
• Has evaluable or measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria or mRECIST criteria for pleural mesothelioma (Appendix 2).
• Tumor tissue and/or archival tissue, ideally from original diagnostic block or the patients most recent biopsy, must be located with plans to be forwarded to the study center or made available prior to the first dose of study therapy and available for biomarker analysis. Archival biopsy samples are only required for patients enrolled in Part 1 or 2.
• Performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) scale (Appendix 1).
• Normal auditory acuity: defined as a normal age-related audiogram.
• Must have adequate bone marrow and renal/hepatic function at the screening and baseline visits, defined as:
• Absolute neutrophil count (ANC) ≥1.5×109/L without granulocyte colony stimulating factor (G-CSF) support within 7 days preceding the lab assessment.
• Platelet ≥100×109/L, without transfusion within 7 days preceding the lab assessment.
• Hemoglobin ≥9 g/dL, without transfusion support within 7 days preceding the lab assessment.
• Activated partial thromboplastin time/ partial thromboplastin time (aPTT/PTT) ≤1.5×ULN.

You may not qualify if:

• Individuals will be excluded from study participation if they:
• \) Have a seizure disorder where \>1 seizure has occurred within the last year. 2) Have clinically significant cardiovascular disease (e.g., significant cardiac conduction abnormalities, uncontrolled hypertension, myocardial infarction, cardiac arrhythmia or unstable angina, New York Heart Association Grade 3 or greater congestive heart failure, serious cardiac arrhythmia requiring medication, Grade 2 or greater peripheral vascular disease, or history of cerebrovascular accident \[CVA\]) within 6 months of enrollment.
• \) History or presence of an abnormal ECG that, in the Investigator's opinion, is clinically meaningful. Screening QTcF interval \>480 ms is excluded. In the event that a single QTcF is \>480 ms, the patient may enroll if the average QTcF for the 3 ECGs is \<480 ms. For patients with an intraventricular conduction delay (QRS interval \>120 ms), the JTc interval may be used in place of the QTcF with Sponsor approval. The JTc must be \<340 ms if JTc is used in place of the QTcF. Patients with an intraventricular delay due to a left bundle branch block are excluded. Note: QTcF prolongation due to pacemaker may enroll if the JTc is normal.
• \) Patient with treated (surgically excised or irradiated) and stable brain metastases are eligible as long as the treatment was at least 4 weeks prior to initiation of study drug and baseline brain computed tomography (CT) with contrast or MRI within 2 weeks of initiation of study drug is negative for new brain metastases. Patients with stable brain metastases must not require therapy with corticosteroids.
• \) Have major surgery, other than diagnostic surgery, within 4-weeks prior to Day 1.
• \) Have active, bacterial, viral, or fungal infections, requiring systemic therapy.
• \) Women who are pregnant or lactating. NOTE: Women of childbearing potential (WOCBP) must have a "negative" serum pregnancy test within 1 week prior to treatment.
• a) Women not OCBP defined as any of the following: i. Postmenopausal with \>1 year since last menses and:
• If younger than 65 years old, with a follicle-stimulating hormone (FSH) \>40 mIU/mL.
• If older than 65 years old and not on hormone replacement therapy (HRT), with a FSH \>30 mIU/mL.
• If older than 65 years old and on HRT, the FSH requirement in not applicable. Postmenopausal females on HRT will be allowed if the treatment is stable for at least 6 months prior to dosing of study drug(s).
• Written medical documentation of being sterilized (e.g. hysterectomy, double oophorectomy, bilateral salpingectomy) with the procedure performed at least 6 months prior to dosing study drug(s). Note: Tubal ligation is not considered a form of permanent sterilization.
• Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
• \) Have undergone treatment with radiation therapy, surgery, chemotherapy, or immunotherapy, within 4-weeks prior to study entry (6 weeks for nitrosoureas or Mitomycin C). Patients may also not have any unresolved toxicity \>Grade 1 from previous anticancer therapy, except for stable chronic toxicities that are not expected to resolve (i.e. peripheral neuropathy, alopecia etc.). Patients who have an ongoing requirement for thyroid replacement therapy from prior exposure to a checkpoint inhibitor but who are clinically euthyroid are permitted.
• \) Have an unwillingness or inability to comply with procedures required in this protocol.

Sponsors & Collaborators

• Aminex Therapeutics, Inc.: lead

Study Sites (4)

Next Oncology - Austin Midtown

Austin, Texas, 78758, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Next Oncology - San Antonio

San Antonio, Texas, 78240, United States

Location

Virginia Cancer Center

Fairfax, Virginia, 22031, United States

Location

Related Publications (1)

• Piha-Paul SA, Tolcher AW, Vandross AL, Spira AI, Burns MR. Phase I dose-escalation trial of AMXT 1501 dicaprate plus difluoromethylornithine: a dual-agent approach targeting immunosuppressive polyamine metabolism. ESMO Open. 2025 Sep;10(9):105576. doi: 10.1016/j.esmoop.2025.105576. Epub 2025 Sep 6.

  PMID: 40913836 DERIVED

MeSH Terms

Conditions

Neoplasms

Study Officials

• Nicole Gallegos, BS, MBA

  Aminex

  STUDY DIRECTOR

• Jackie Walling, MBChB PhD

  Aminex

  STUDY CHAIR

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: April 4, 2018
• First Posted: May 25, 2018
• Study Start: June 12, 2018
• Primary Completion: December 30, 2022
• Study Completion: April 21, 2023
• Last Updated: May 25, 2023

Record last verified: 2023-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)