Oral AMXT 1501 Dicaprate in Combination With IV DFMO

Phase 1

Terminated

• Conditions: Advanced Cancer; DIPG Brain Tumor; Ovary Cancer; Mesotheliomas Pleural; Papillary Thyroid Cancer; Gastric Cancer; Mesothelioma Peritoneum; Cancer; Nsclc; Cervical Cancer
• Interventions: Drug: AMXT1501; Drug: DFMO

• Registration Number: NCT05500508
• Lead Sponsor: Aminex Therapeutics, Inc.

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.

Detailed Description

The objective of this study is to determine the safety and tolerability of oral AMXT 1501 dicaprate (AMXT1501) in combination with IV DFMO in patients with advanced solid tumors, or DIPG/DMG. Secondary objectives include characterization of plasma pharmacokinetics (PK), pharmacodynamic (PD), and other biomarker efficacy assessments of the impact of AMXT 1501 in combination with IV DFMO on polyamine uptake by circulating lymphocytes (blood cells). To these aims, the study will evaluate the safety, PK, PD, and other biomarker efficacy profiles of orally-administered AMXT 1501 and IV DFMO. Approximately, 56 patients will be enrolled to determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of AMXT 1501 and IV DFMO in combination. The MTD is defined as the highest dose level below at which dose escalation is stopped.

Study Timeline

• Study First Submitted: 2022-08-10
• Study First Submitted QC: 2022-08-12
• Study First Posted: 2022-08-15
• Study Start: 2022-11-29
• Status Verified: 2024-12
• Primary Completion: 2024-12-12
• Study Completion: 2024-12-12
• Last Update Submitted: 2024-12-19
• Last Update Posted: 2024-12-24

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 15

Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Escalation	AMXT1501	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.
Expansion	AMXT1501	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.
Escalation	DFMO	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.
Expansion	DFMO	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.

Primary Outcome Measures

Name	Time	Method
Determine safety and tolerability of AMXT1501 in combination with IV DFMO	1 year	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
Determine DLTs and RP2Ds in AMXT 1501 in combination with IV DFMO	1 year	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

Secondary Outcome Measures

Name	Time	Method
Characterize investigator defined response Overall Response Rate (ORR) using RECIST v1.1	6 months	To characterize Investigator defined Overall Response Rate (ORR) using RECIST v1.1 response criteria.
Characterize investigator defined Duration of Response (DOR)	6 months	To characterize Investigator defined Duration of Response (DOR), using RECIST v1.1 response criteria and length of time (in days) from last study drug administration to time patient has progressive disease.
Determine the PK using AUC of AMXT 1501 and IV DFMO	6 months	To evaluate the pharmacokinetics (PK) of AMXT 1501 in combination with IV DFMO in patients
Determine the PK using Cmax of AMXT 1501 and IV DFMO	6 months	To evaluate the pharmacokinetics (PK) of AMXT 1501 and IV DFMO
Characterize AMXT1501 and IV DFMO on the expression of immune related gene signatures	1 year	Evaluate the effects of AMXT1501 and IV DFMO on the expression of immune related gene signatures, immune cell phenotype by IHC, AMXT1501 and DFMO drug levels impact on polyamine levels

Trial Locations

Locations (7)

Mayo Clinic - Minnesota; 🇺🇸 Rochester, Minnesota, United States

Cincinnati Children's Hospital Medical Center; 🇺🇸 Cincinnati, Ohio, United States

Mayo Clinic - Florida; 🇺🇸 Jacksonville, Florida, United States

Mayo Clinic - Arizona; 🇺🇸 Phoenix, Arizona, United States

MD Anderson Cancer Center; 🇺🇸 Houston, Texas, United States

Fred Hutch Cancer Center - Seattle Cancer Care Alliance; 🇺🇸 Seattle, Washington, United States

Kids Cancer Centre; 🇦🇺 Sydney, New South Wales, Australia