RecruitingInterventionalPhase 1/Phase 2

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

NCT ID: NCT04503265Sponsor: AtlasMedx, IncorporatedLast updated: 2025-05-01

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.

Detailed 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.

Arms & interventions

DrugAMXI-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.
DrugAMXI-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.

Outcome measures

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.
Time frame: Approximately 12 months
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.
Time frame: Approximately 12 months
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.
Time frame: Approximately 24 months

Secondary

Measure concentration of AMXI-5001 in plasma samples
Time frame: Approximately 24 months
Determine change in anti-tumor activity following administration of AMXI-5001
Time frame: Approximately 24 months

Eligibility criteria

Sex: AllAge: 18 Years and olderHealthy volunteers: No

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 5. Able to understand and sign consent 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

Study locations (4)

University of California, Los Angles (UCLA) Department of Medicine - Hematology/Oncology

Los Angeles, California, 90404

Recruiting

Johns Hopkins

Baltimore, Maryland, 21218

Recruiting

SCRI Oncology Partners

Nashville, Tennessee, 37203

Recruiting

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030

Recruiting

References

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.(PubMed)