Phase 1, First-in-Human Study of RAD140 in Postmenopausal Women With Breast Cancer

Study Overview
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Brief Summary
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The primary purpose of this study is to evaluate the clinical safety profile, tolerability, and pharmacokinetic (PK) characteristics of RAD140 in hormone receptor positive breast cancer.

Detailed Description
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This is a first in humans study that is designed to evaluate the clinical safety profile, tolerability, and pharmacokinetic (PK) characteristics of RAD140 in hormone receptor positive breast cancer.

Official Title
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A Phase 1, First-in-Human, Multi-Part Study of RAD140 in Postmenopausal Women With Hormone Receptor Positive Breast Cancer

Conditions
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Hormone Receptor Positive Malignant Neoplasm of Breast

Intervention / Treatment
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* Drug: RAD140


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Progressive metastatic or locally advanced or metastatic breast cancer. Clinically confirmed as postmenopausal. Eastern Cooperative Oncology Group (ECOG) score of 0 to 1 at screening. Key Exclusion Criteria: HER2 positive patients by local laboratory testing. Triple negative breast cancer. Any chemotherapy within the 28 days prior to the first dose of study drug. Any non-chemotherapy anti-cancer drug less than 5 half-lives (30 days for biologics) or less than 14 days for small molecule therapeutics, or if half-life is not known. Tamoxifen and aromatase inhibitors within 14 days prior to the first dose of study drug. Fulvestrant within 30 days prior to first dose of study drug. Any investigational drug therapy within 5 half-lives of the previous investigational study drug or 30 days, whichever is shorter. Radiation therapy for breast cancer within 2 weeks of dosing and planning to have radiation therapy during participation in this study. Known history of human immunodeficiency virus infection (HIV) or hepatitis C or active hepatitis B infection, unless the patient was diagnosed >10 years prior to enrollment and no evidence of active liver disease. Currently taking testosterone, methyltestosterone, oxandrolone (Oxandrin), oxymetholone, danazol, fluoxymesterone (Halotestin), or testosterone-like agents. Untreated or uncontrolled brain metastasis. Diagnosed with or treated for cancer within the previous 2 years, other than breast cancer or non-melanoma carcinoma of the skin. Pregnant and nursing females.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

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: RAD140 Part A and Part B<br>Part A, Dose Escalation: Patients will be assigned sequentially to escalating doses of RAD140. Part B, Safety Expansion: Once the maximum tolerated dose (MTD) has been identified and/or a recommended dose escalation (RDE) has been determined, additional patients will be enrolled to further evaluate the safety, tolerability and preliminary clinical activity of the recommended dose. | Drug: RAD140<br>* RAD140 will be supplied as formulated drug-in-capsules for oral administration.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence rate of dose-limiting toxicities (DLTs) RAD140 treatment | Incidence rate of dose-limiting toxicities (DLTs) RAD140 treatment | First 28 days of treatment | 
| Number of adverse events related to study treatment | Number of adverse events related to study treatment | Up to 30 days after end of treatment | 
| Number participants with dose interruptions and dose adjustments | Number participants with dose interruptions and dose adjustments | Up to 30 days after end of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum plasma concentration (Cmax) | Maximum plasma concentration (Cmax) | Day 1 and 15 | 
| Time to maximum plasma concentration (Tmax) | Time to maximum plasma concentration (Tmax) | Day 1 and 15 | 
| Area under the plasma concentration versus time curve (AUC) | Area under the plasma concentration versus time curve (AUC) | Day 1 and Day 15 | 
| Tumor response | Clinical benefit rate (CBR) or objective response rate (ORR) will be assessed by Investigators per RECIST v1.1 along with time-related efficacy endpoints. | Screening and every 8 weeks for up to 12 months of treatment |