A Study to Determine Safety and Tolerability of GMI-1359 in Subjects With HR+ Metastatic Breast Cancer

Study Overview
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Brief Summary
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This trial is being conducted to investigate the safety, tolerability, pharmacokinetics (the effect the body has on the drug), and pharmacodynamics (the effect the drug has on the body) of GMI-1359 when given with standard-of-care treatment to subjects with HR+ metastatic breast cancer.

Official Title
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A Phase 1b, Single and Multiple Dose, Open-Label Trial of Intravenous GMI-1359 in HR+ Metastatic Breast Cancer Subjects

Conditions
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HR+ Metastatic Breast Cancer, Breast Cancer, Breast Cancer Metastatic

Intervention / Treatment
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* Drug: GMI-1359


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Pathologically confirmed HR+ metastatic breast cancer, currently stable or minimally progressive on current endocrine-based therapy. Continuing on current endocrine-based therapy with an aromatase inhibitor, selective estrogen receptor degrader, or selective estrogen receptor modulator; and must be medically eligible to remain on this therapy during the treatment period. Exclusion Criteria: Uncontrolled acute life-threatening bacterial, viral, or fungal infection. Subjects who are pregnant or breastfeeding Concurrent treatment with any cytotoxic chemotherapy agent or other targeted therapies including HER2 targeting therapies Currently receiving, or less than 28 days since ending treatment on another investigational drug. Clinically significant cardiovascular disease. Abnormal liver function. Any medical, psychiatric, or other condition which, in the opinion of the investigator, is likely to interfere with trial completion, assessments, or interpretation of trial results, or otherwise would make the subject an inappropriate subject for this trial.

Ages Eligible for Study
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Minimum Age: 18 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: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Single Ascending Dose followed by Multiple Doses<br>Up to 3 single ascending doses of GMI-1359 followed by the highest tolerated dose given for 3 consecutive days. | Drug: GMI-1359<br>* Injection 10 mg/mL<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Occurrences of dose-limiting toxicities (DLT) including protocol-defined adverse events (AEs)/serious adverse events (SAEs), and/or laboratory abnormalities will be assessed in order to determine recommended phase II dose (Safety and Tolerability) |  | Up to 4 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the plasma concentration-time curve [AUC0-t and AUC0-∞] of GMI-1359 |  | Up to 16 weeks | 
| Maximum plasma concentration [Cmax] of GMI-1359 |  | Up to 16 weeks | 
| Time to reach maximum plasma concentration [tmax] of GMI-1359 |  | Up to 16 weeks | 
| Individual estimate of the terminal elimination rate constant [Λz] of GMI-1359 |  | Up to 16 weeks | 
| Half-life [t1/2] of GMI-1359 |  | Up to 16 weeks | 
| Total plasma clearance [CL] of GMI-1359 |  | Up to 16 weeks | 
| Apparent volume of distribution estimated at the terminal phase [Vz] of GMI-1359 |  | Up to 16 weeks | 
| Pre- and post-dose circulating tumor cells (CTC) enumeration to determine tumor cell mobilization [digital pathology assay] |  | Up to 16 weeks | 
| Pre-and post-dose CD34+ cell quantification to determine mobilization into peripheral blood [standard flow cytometry] |  | Up to 16 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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GMI-1359, breast cancer, HR+ metastatic breast cancer