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

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

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:

1. To evaluate the safety and tolerability of AC682
2. To evaluate the pharmacokinetic of AC682
3. To evaluate the preliminary anti-tumor activity of AC682

Study Overview

• Status: Terminated
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: AC682

Detailed Description

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

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Beijing, China
    • Site 1001
  • Hangzhou, China
    • Site 1003
  • Tianjin, China
    • Site 1002

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Patients must be ≥18 years-of-age at the time of signing of the ICF
2. Histologically and/or cytologically confirmed advanced estrogen receptor positive (ER+) human epidermal growth factor 2 negative (HER2-) breast cancer
3. Female patients must be postmenopausal
4. 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
5. 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.
6. Patients who have adequate organ functions at baseline

Exclusion Criteria:

1. 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)

2. Received radiotherapy (including radioactive isotope therapy) within 4 weeks prior to the first dose of AC682
3. Major surgery (excluding placement of vascular access) within 4 weeks of first dose of AC682
4. With known metastasis to the brain
5. 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.
6. Use of prophylactic growth factors and blood transfusions ≤14 days prior to the first dose of AC682 and during dose limiting toxicity observation period

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: AC682; This arm will evaluate AC682 monotherapy administered in 28-day cycles. The participants will participate in this dose escalation arm.	Drug: AC682; Participants will receive AC682 by mouth daily in 28-day cycles.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Accutar Biotechnology Inc

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2022
• Primary Completion (Actual): September 28, 2023
• Study Completion (Actual): September 28, 2023

Study Registration Dates

• First Submitted: July 15, 2022
• First Submitted That Met QC Criteria: August 3, 2022
• First Posted (Actual): August 5, 2022

Study Record Updates

• Last Update Posted (Estimated): January 25, 2024
• Last Update Submitted That Met QC Criteria: January 23, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: Phase I; HER2 negative; Estrogen receptor positive; ER positive; ER+; Human epidermal growth factor receptor 2 negative; AC682
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms
• Other Study ID Numbers: AC682-002

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No