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

Study Overview
=================
Brief 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.

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

Conditions
-----------------
Breast Cancer, Advanced Malignant Neoplasm, Ovarian Cancer, Homologous Recombination Deficiency, Prostate Cancer, Pancreatic Cancer

Intervention / Treatment
-----------------
* Drug: AMXI-5001:Dose Escalation Phase I
* Drug: AMXI-5001:Dose Expansion Phase II


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria (Key Factors): Has pathologically confirmed advanced or metastatic malignancy characterized by one or more of the following: Patient is intolerant of existing therapy(ies) known to provide clinical benefit for their condition Malignancy is refractory to existing therapy(ies) known to potentially provide clinical benefit Malignancy has progressed after standard therapy Has evaluable or measurable tumor(s) in dose escalation by standard radiological and/or laboratory assessments as applicable to their malignancy. Eastern Co-operative Oncology Group (ECOG) PS 0-1 Participant must be 18 years of age or older Exclusion Criteria (Key Factors): Receiving cancer treatment at the time of enrollment Any clinically significant disease or condition affecting a major organ system Significant cardiovascular disease or electrocardiogram (ECG) abnormalities 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) Has had a previous (within 2 years) or has a current malignancy other than the target cancer

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AMXI-5001 Treatment<br>Single Arm Study, all participants will receive AMXI-5001. | Drug: AMXI-5001:Dose Escalation Phase I<br>* 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.<br>* Other names: Dose Escalation;Drug: AMXI-5001:Dose Expansion Phase II<br>* 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.<br>* Other names: Dose Expansion;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 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 | 
| 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 | 
| 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 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Breast, Ovarian, Prostate, Pancreatic, Refractory, Cancer, Malignancy, BRCA, HRD, AMXI-5001, Progression, PARP Inhibitor, Microtubule inhibitor