A Study of Oral MBQ-167 in Participants With Advanced Breast Cancer

Study Overview
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Brief Summary
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A Phase 1, open-label, dose-escalation clinical trial of MBQ-167 in participants with advanced Breast Cancer for whom Standard of Care (SOC) has failed or has proven intolerable.

Detailed Description
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The main questions this clinical trial aims to answer are: What, if any, are the side effects of different dose levels in humans? What is the maximum tolerated dose? How does the human body process the drug? Does the drug slow, stop or eliminate cancer in human participants? Participants will be asked to: provide informed consent be evaluated by physicians and provide laboratory specimens to determine if eligible take MBQ-167 orally twice a day for at least 21 days may continue dosing, if safe to do so, until not effective or other decision to stop is made participate in multiple visits that include additional evaluations, laboratory tests and diary review until after stopping the investigational drug

Official Title
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A Phase 1 Open-Label, First-in-Human Trial of Oral MBQ-167 as Single Agent in Participants With Advanced Breast Cancer

Conditions
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Breast Cancer, Breast Neoplasm, Breast Cancer Stage IV

Intervention / Treatment
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* Drug: MBQ-167


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: The investigator will evaluate these and other criteria to determine whether a participant can be included in this study. Histologically and/or cytologically confirmed advanced breast cancer which has progressed after treatment with approved therapies or for which there are no standard therapies available. Participants with known brain metastases may be eligible if specific conditions are met. Life expectancy ≥6 months, in the opinion of the investigator, after starting MBQ-167. Are able to swallow capsules twice daily. Key Exclusion Criteria: The investigator will evaluate these and other criteria to determine whether a participant should be excluded from this study. Inability to take oral medication, or malabsorption syndrome or any other uncontrolled gastrointestinal condition (e.g., nausea, diarrhea, or vomiting) that might impair the bioavailability of MBQ-167. Females who are pregnant or breastfeeding. Participants who have received any anticancer treatment within 4 weeks or any investigational agent within 30 days prior to the first dose of trial drug or who have not recovered from any acute toxicity greater than Grade 0 or 1 related to previous anticancer treatment. Participants who have received any anticancer treatment within 4 weeks or any investigational agent within 30 days prior to the first dose of trial drug or who have not recovered from any acute toxicity greater than Grade 0 or 1 related to previous anticancer treatment. Active malignancies other than advanced breast cancer will be excluded from the study.

Ages Eligible for Study
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Minimum Age: 21 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Sequential Assignment
Interventional Model Description: Open-label dose escalation following a standard 3+3 cohort design with a 21 day Dose Limiting Toxicity (DLT) evaluation
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MBQ-167 oral capsule<br>A dose ranging from 10mg to 400mg BID following a standard 3+3 cohort design | Drug: MBQ-167<br>* MBQ-167, an inhibitor of Rho GTPases Rac and Cdc42<br>* Other names: Rac/Cdc42 inhibitor;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Tolerated Dose (MTD) | To find the maximum tolerated dose (MTD) of MBQ-167 as a single agent administered orally, BID continuously for 21 days in participants with Advanced Breast Cancer (ABC) by evaluating for the presence or absence of dose-limiting toxicity (DLT) related to MBQ-167 administered in cohorts of participants at escalating sequential cohort dose levels. | 21 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| MBQ-167 PK parameter (Cmax/min) | Maximum and minimum observed plasma concentration at steady state | 56 days | 
| MBQ-167 PK parameter (tmax) | Time to maximum plasma concentration | 56 days | 
| MBQ-167 PK parameter (t1/2) | Terminal elimination half-life | 56 days | 
| MBQ-167 PK parameter (AUC (0-t,0-24,∞)) | Area under the concentration-time curve over the dosing interval time from time 0 | 56 days | 
| MBQ-167 PD parameter (differential gene expression) | Observed quantitative measurement of gene expression change from baseline | 16 days | 
| MBQ-167 PK/PD parameter (minimum dose for therapeutic response) | Correlate differential gene expression change, objective response and PK parameter Cmax/min to identify a minimum dose for therapeutic response | 56 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Recurrent Breast Cancer, Advanced Breast Cancer, Metastatic Breast Cancer