A Study of AC682 In Chinese Patients With ER+/HER2- Locally Advanced or Metastatic Breast Cancer

Study Overview
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Brief Summary
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This clinical trial is evaluating AC682 in participants with estrogen receptor positive/human epidermal growth factor 2 negative (ER+/HER2-) locally advanced or metastatic breast cancer. The main goals of this study are to: To evaluate the safety and tolerability of AC682 To evaluate the pharmacokinetic of AC682 To evaluate the preliminary anti-tumor activity of AC682

Detailed Description
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This is a Phase I, open-label dose-escalation study of AC682, an orally available estrogen receptor degrader, given as a single agent.

Official Title
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A Phase I Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Preliminary Anti-Tumor Activity of AC682 In Chinese Patients With ER+/HER2- Locally Advanced or Metastatic Breast Cancer

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: AC682


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients must be ≥18 years-of-age at the time of signing of the ICF Histologically and/or cytologically confirmed advanced estrogen receptor positive (ER+) human epidermal growth factor 2 negative (HER2-) breast cancer Female patients must be postmenopausal At least 1 measurable lesion according to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 or at least 1 predominantly lytic bone lesion in the absence of measurable disease Previously received at least 1 endocrine therapy regimen; concomitant use of cyclin-dependent kinase (CDK) 4/6 inhibitor(s) is acceptable; Previous chemotherapy is not required, but up to 2 prior regimens of cytotoxic chemotherapy is allowed. Patients who have adequate organ functions at baseline Exclusion Criteria: Treatment with any of the following: systemic anti-cancer chemotherapy, biologic, or hormonal agent from a previous treatment regimen or clinical study within 4 weeks prior to the first dose of AC682; systemic small molecules from a previous treatment regimen or clinical study within 14 days or 5 half-lives (whichever is longer) prior to the first dose of AC682 (at least 10 days must have elapsed between the last dose of such agent and the first dose of study drug) Received radiotherapy (including radioactive isotope therapy) within 4 weeks prior to the first dose of AC682 Major surgery (excluding placement of vascular access) within 4 weeks of first dose of AC682 With known metastasis to the brain Any condition that impairs a patient's ability to swallow whole pills. Impairment of gastrointestinal function (GI) or GI disease or other condition at baseline that will interfere significantly with the absorption, distribution, or metabolism of AC682. Use of prophylactic growth factors and blood transfusions ≤14 days prior to the first dose of AC682 and during dose limiting toxicity observation period

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: AC682<br>This arm will evaluate AC682 monotherapy administered in 28-day cycles. The participants will participate in this dose escalation arm. | Drug: AC682<br>* Participants will receive AC682 by mouth daily in 28-day cycles.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of dose limiting toxicities (DLTs) from AC682 monotherapy | Number of subjects with DLT | 28 days | 
| Incidence of treatment emergent adverse events(TEAEs) from AC682 monotherapy | Number of adverse events as characterized by type, frequency, seriousness, and relationship to AC682 | Throughout the study completion, approximately 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To determine the PK of AC682 after a single dose or multiple doses: | Area under the plasma concentration-time curve from time zero extrapolated to infinity (AUC(0-inf)) | At predefined intervals throughout the study completion, approximately 24 months. | 
| To determine the PK of AC682 after a single dose or multiple doses: | Area under the concentration-time curve over the dosing interval (AUC(0-tau)) | At predefined intervals throughout the study completion, approximately 24 months. | 
| To determine the PK of AC682 after a single dose or multiple doses: | Maximum plasma concentration (Cmax) | At predefined intervals throughout the study completion, approximately 24 months. | 
| To determine the PK of AC682 after a single dose or multiple doses: | Time to maximum plasma concentration (tmax) | At predefined intervals throughout the study completion, approximately 24 months. | 
| To determine the PK of AC682 after a single dose or multiple doses: | Terminal elimination half life (t1/2) | At predefined intervals throughout the study completion, approximately 24 months. | 
| To evaluate the preliminary anti-tumor activity of AC682: | Objective Response Rate(ORR) using RECIST version 1.1 | Throughout the study completion, approximately 24 months | 
| To evaluate the preliminary anti-tumor activity of AC682: | Clinical Benefit Rate (CBR) using RECIST version 1.1 | Throughout the study completion, approximately 24 months | 
| To evaluate the preliminary anti-tumor activity of AC682: | Duration of Response (DoR) using RECIST version 1.1 | Throughout the study completion, approximately 24 months | 
| To evaluate the preliminary anti-tumor activity of AC682: | Disease Control Rate (DCR) using RECIST version 1.1 | Throughout the study completion, approximately 24 months | 
| To evaluate the preliminary anti-tumor activity of AC682: | Progression-free Survival (PFS) using RECIST version 1.1 | Throughout the study completion, approximately 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Estrogen receptor positive, ER positive, ER+, Human epidermal growth factor receptor 2 negative, HER2 negative, AC682, Phase I