Oral AMXT 1501 Dicaprate in Combination With IV DFMO

NCT05500508 | Terminated Phase 1 DMC FDA Drug

• 1 other identifier: AMXT1501-102
• Study Type: interventional
• Target: 15
• Locations: 2 countries
• Sites: 7

Brief Summary

A Phase 1B/2A study will be conducted to establish safety and dose level of AMXT 1501 dicaprate in combination with IV DFMO, in cancer patients.

Conditions

Cancer; Solid Tumor; Solid Carcinoma; Advanced Cancer; DIPG Brain Tumor; Ovary Cancer; Breast Cancer; Papillary Thyroid Cancer; Head and Neck Cancer; Gastric Cancer; Nsclc; Mesotheliomas Pleural; Mesothelioma Peritoneum; Esophageal Cancer; Diffuse Midline Glioma, H3 K27M-Mutant; Endometrial Cancer; Cervical Cancer; Melanoma; Colorectal Cancer; Glioma, Malignant

Keywords

DFMO IV; AMXT 1501; DFMO

Outcome Measures

Primary Outcomes (2)

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

  Indicate Number of patients with DLTs in AMXT1501 in combination with IV DFMO in patients with advanced cancer to determine the RP2D within the duration of the dose escalation period of the study as defined by the DLT definition of the protocol from baseline to end of Cycle 1

  1 year

• Determine safety and tolerability of AMXT1501 in combination with IV DFMO

  To evaluate the safety and tolerability of AMXT1501 and IV DFMO combination in patients through collecting the number of patients with Treatment Related Adverse Events that occur in patients from first dose, AEs assessed by CTCAEv5.0

  1 year

Secondary Outcomes (5)

• Determine the PK using AUC of AMXT 1501 and IV DFMO

  6 months

• Determine the PK using Cmax of AMXT 1501 and IV 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 and IV DFMO on the expression of immune related gene signatures

  1 year

Other Outcomes (1)

• Evaluate AMXT1501 and DFMO on PD biomarker by evaluating the level/concentration of polyamine uptake.

  6 months

Study Arms (2)

Escalation

EXPERIMENTAL

Dose escalation of DFMO with AMXT1501 fixed dose will follow a 3 + 3 dose escalation design. The AMXT 1501 starting dose administered in the first cohort will be 1200mg total daily dose (200 mg capsules; 3 capsules in morning; 3 capsules in evening) along with IV DFMO administered in continuous infusion at 2mL/hr over a 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 cohort.

Drug: AMXT1501; Drug: DFMO

Expansion

EXPERIMENTAL

The expansion cohort will include up to 40 evaluable patients at a proposed RP2D level of AMXT1501 and DFMO defined by AMXT1501-101A study 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 200 mg (free base content) enterically-coated capsules

Escalation; Expansion

DFMO DRUG

DFMO is DL-2-(difluoromethyl) ornithine monohydrochloride monohydrate provided as a 200 mg/mL aqueous solution in 20 mL vials.

Also known as: difluoromethyl ornithine monohydrochloride

Escalation; Expansion

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:

• IMPORTANT NOTE- Younger 12-17 year old patients are also eligible for this study if they meet the noted DIPG or DMG criteria noted below, which is separate from Patient Diagnosed with Advanced Solid Tumors.
• Understand and sign written IRB-approved informed consent form and be willing to comply with all study procedures.
• Diagnosed with unresectable, locally advanced, or metastatic solid tumor for which no standard therapy is recognized or for which standard therapy has failed. Planned tumor types for evaluation include:
• Platinum resistant ovarian cancer (including - primary peritoneal cancer and fallopian tube cancer)
• Breast cancer
• Papillary thyroid cancer
• Head and neck cancer
• Gastric cancer
• Non-small cell lung cancer (NSCLC)
• Mesothelioma: Pleural and peritoneal
• Esophageal
• Endometrial cancer
• Cervical
• Melanoma
• Colorectal cancers (colon, rectal)

You may not qualify if:

• Patients must have fully recovered from the acute toxic effects of all prior anti-cancer chemotherapy: The following minimum periods from treatment apply:
• (a) Myelosuppressive chemotherapy: At least 21 days after the last dose of myelosuppressive chemotherapy (42 days if prior nitrosourea).
• (b) Hematopoietic growth factors: At least 14 days after the last dose of a long-acting growth factor (e.g., Neulasta) or 7 days for short-acting growth factor.
• (c) Biologic (anti-neoplastic agent): At least 7 days after the last dose of a biologic agent. For agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur.
• (d) Immunotherapy: At least 42 days after the completion of any type of vaccination.
• (e) Monoclonal antibodies: \>21 days must have elapsed from the infusion of last dose of antibody and toxicity related to antibody therapy must be recovered to Grade ≤1.
• (f) Radiation therapy: Patients must have had their last fraction of craniospinal or focal irradiation a minimum of 8-12 weeks prior to enrollment.
• (g) Stem cell transplant: Patients must be ≥3 months since autologous stem cell transplant. Patients who received allogenic stem cell transplant or solid organ transplant are not eligible for study.
• Patient is able to take oral medications and willing to use an at-home infusion pump.
• Must have adequate bone marrow and renal/hepatic function at the screening and baseline visits, defined as:
• (a) Absolute neutrophil count (ANC) ≥1.5×109/L without granulocyte colony-stimulating factor (G-CSF) support within 7 days
• (b) Platelet ≥100×109/L, without transfusion within 7 days
• (c) Hemoglobin ≥9 g/dL, without transfusion support within 7 days
• (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).

Sponsors & Collaborators

• Aminex Therapeutics, Inc.: lead

Study Sites (7)

Mayo Clinic - Arizona

Phoenix, Arizona, 85054, United States

Location

Mayo Clinic - Florida

Jacksonville, Florida, 32224, United States

Location

Mayo Clinic - Minnesota

Rochester, Minnesota, 55905, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Fred Hutch Cancer Center - Seattle Cancer Care Alliance

Seattle, Washington, 98109, United States

Location

Kids Cancer Centre

Sydney, New South Wales, Australia

Location

MeSH Terms

Conditions

Neoplasms; Diffuse Intrinsic Pontine Glioma; Ovarian Neoplasms; Breast Neoplasms; Thyroid Cancer, Papillary; Head and Neck Neoplasms; Stomach Neoplasms; Carcinoma, Non-Small-Cell Lung; Mesothelioma, Malignant; Esophageal Neoplasms; Endometrial Neoplasms; Uterine Cervical Neoplasms; Melanoma; Colorectal Neoplasms; Glioma

Condition Hierarchy (Ancestors)

Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Brain Stem Neoplasms; Infratentorial Neoplasms; Brain Neoplasms; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Endocrine Gland Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Adenocarcinoma, Papillary; Adenocarcinoma; Carcinoma; Thyroid Neoplasms; Thyroid Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases; Mesothelioma; Adenoma; Neoplasms, Mesothelial; Pleural Neoplasms; Esophageal Diseases; Uterine Neoplasms; Uterine Diseases; Uterine Cervical Diseases; Neuroendocrine Tumors; Nevi and Melanomas; Skin Neoplasms; Intestinal Neoplasms; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Study Officials

• Sue Lee, MD

  Aminex Therapeutics, Inc.

  STUDY CHAIR

• Michael Armstrong, MD

  IQVIA Biotech

  STUDY DIRECTOR

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: August 10, 2022
• First Posted: August 15, 2022
• Study Start: November 29, 2022
• Primary Completion: December 12, 2024
• Study Completion: December 12, 2024
• Last Updated: December 24, 2024

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (6); AU (1)