A Trial of AMXI-5001 for Treatment in Patients With Advanced Malignancies

Breast Cancer Clinical Trial

Official title:

A Phase I/II, Open Label, Multi-center, Non-randomized Dose Escalation and Dose Expansion Study of AMXI-5001 in Patients With Advanced Malignancies

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04503265
• Other study ID #: ATLAS-101
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• Start date: August 12, 2020
• Est. completion date: January 2025

Study information

• Verified date: March 2024
• Source: AtlasMedx, Incorporated
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

ATLAS-101 is a Phase I/II clinical trial of AMXI-5001 in adult participants with advanced malignancies who have previously failed other therapies. The study has two phases. The purpose of Phase I (Dose Escalation) is to confirm the appropriate treatment dose and Phase II (Dose Expansion) is to characterize the safety and efficacy of AMXI-5001.

Description:

AMXI-5001 is an orally available dual PARP (poly adenosine diphosphate [ADP] ribose polymerase) and microtubule polymerization inhibitor. ATLAS-101 is a Phase I/II, open label, multi-center, non-randomized Dose Escalation and Dose Expansion study in participants with advanced malignancies. Study enrollment is approximately 122 participants. All participants receive oral AMXI-5001, twice daily, as monotherapy. Following Phase I (Dose Escalation) to identify the Maximum Tolerated Dose and the Recommended Dose for use in Phase II, additional participants will be enrolled into the Dose Expansion Phase to further characterize the safety, pharmacology, and clinical efficacy of AMXI-5001.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 122
• Est. completion date: January 2025
• Est. primary completion date: January 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria (Key Factors):

1. Has pathologically confirmed advanced or metastatic malignancy characterized by one or

more of the following:

1. Patient is intolerant of existing therapy(ies) known to provide clinical benefit for their condition

2. Malignancy is refractory to existing therapy(ies) known to potentially provide clinical benefit

3. Malignancy has progressed after standard therapy

2. Has evaluable or measurable tumor(s) in dose escalation by standard radiological and/or laboratory assessments as applicable to their malignancy.

3. Eastern Co-operative Oncology Group (ECOG) PS 0-1

4. Participant must be 18 years of age or older

Exclusion Criteria (Key Factors):

1. Receiving cancer treatment at the time of enrollment

2. Any clinically significant disease or condition affecting a major organ system

3. Significant cardiovascular disease or electrocardiogram (ECG) abnormalities

4. Use of a strong inhibitor or inducer of CYP3A4 within 7 days prior to start of study therapy and throughout the study (e.g., some antibiotics, antifungals, anticonvulsants, grapefruit)

5. Has had a previous (within 2 years) or has a current malignancy other than the target cancer

Related Conditions & MeSH terms

• Advanced Malignant Neoplasm
• Breast Cancer
• Homologous Recombination Deficiency
• Neoplasms
• Ovarian Cancer
• Pancreatic Cancer
• Prostate Cancer

Intervention

Drug:
• AMXI-5001:Dose Escalation Phase I
Phase I will enroll up to 70 participants to identify the Recommended Phase II daily dose in the treatment of various cancers and to characterize the safety, pharmacology, and clinical efficacy of AMXI-5001. AMXI-5001 is administered orally twice daily, with food. AMXI-5001 is administered weekly on a continuous 7-day schedule. Each cycle is 28 days.
• AMXI-5001:Dose Expansion Phase II
Phase II will enroll up to 52 study participants to further characterize the safety, pharmacology, and clinical efficacy of AMXI-5001. AMXI-5001 is administered orally twice daily, with food. AMXI-5001 is administered weekly on a continuous 7-day schedule. Each cycle is 28 days.

Locations

Country	Name	City	State
United States	Johns Hopkins	Baltimore	Maryland
United States	University of California, Davis (UC Davis)	Davis	California
United States	The University of Texas MD Anderson Cancer Center	Houston	Texas
United States	University of California, Los Angles (UCLA) Department of Medicine - Hematology/Oncology	Los Angeles	California
United States	SCRI Oncology Partners	Nashville	Tennessee
United States	Vanderbilt University	Nashville	Tennessee
United States	Honor Health	Phoenix	Arizona
United States	Moffitt Cancer Center and Research Institute	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
AtlasMedx, Incorporated

Country where clinical trial is conducted

United States, 

References & Publications (1)

Lemjabbar-Alaoui H, Peto CJ, Yang YW, Jablons DM. AMXI-5001, a novel dual parp1/2 and microtubule polymerization inhibitor for the treatment of human cancers. Am J Cancer Res. 2020 Aug 1;10(8):2649-2676. eCollection 2020. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Determine the Maximum Tolerated Dose (MTD)	The highest dose is defined at which no more than 1 of 6 evaluable participants has had a Dose Limiting Toxicity (DLT) according to NCI CTCAE V5.0 criteria and determination by Investigator and Data and Safety Monitoring Committee.	Approximately 12 months
Secondary	Determine the Recommended Phase 2 Dose (RP2D) for AMXI-5001 as monotherapy	The RP2D is based upon the review of all available data including safety, pharmacokinetic, preliminary anti-tumor activity, and MTD.	Approximately 12 months
Secondary	Measure concentration of AMXI-5001 in plasma samples	Concentrations of AMXI-5001 in plasma samples at different time points are measured. Standard pharmacokinetic parameters are calculated.	Approximately 24 months
Secondary	Characterize safety profile of AMXI-5001	The safety profile of AMXI-5001 is defined by the incidence of treatment emergent adverse events, laboratory abnormalities, and ECG measurements.	Approximately 24 months
Secondary	Determine change in anti-tumor activity following administration of AMXI-5001	Overall Survival (OS), Objective Response Rate (ORR), Duration of Response (DOR), and Progression-free Survival (PFS) are assessed by RECIST V1.1 criteria.	Approximately 24 months

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