A Study of AC682 for the Treatment of Locally Advanced or Metastatic ER+ Breast Cancer

A Phase I Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Preliminary Anti-Tumor Activity of AC682 in Patients With Estrogen Receptor Positive/Human Epidermal Growth Factor Receptor 2 Negative (ER+/HER2-) Locally Advanced or Metastatic Breast Cancer

This clinical trial is evaluating a drug called 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:

• Identify the recommended dose of AC682 that can be given safely to participants
• To evaluate the side effects of AC682
• To evaluate pharmacokinetics of AC682
• To evaluate the effectiveness of AC682

Study Overview

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

Detailed Description

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

• Study Type: Interventional
• Enrollment (Actual): 21
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Colorado
    • Denver, Colorado, United States, 80218
      • Site 01
  • Florida
    • Orlando, Florida, United States, 32827
      • Site 04
    • Sarasota, Florida, United States, 34232
      • Site 02
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Site 03
  • Texas
    • Houston, Texas, United States, 77030
      • Site 05

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Signed written informed consent form (ICF)
• Patients must be ≥18 years-of-age at the time of signing of the ICF
• Female patients must be postmenopausal
• Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1
• Histologically and/or cytologically confirmed advanced estrogen receptor positive (ER+) human epidermal growth factor 2 negative (HER2-) breast cancer
• Patients with life expectancy ≥3 months
• Patients who have adequate organ functions at baseline
• At least 1 measurable lesion that meets the definition in Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 or at least 1 non-target lesion is required.

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)
• Radiation therapy such as wide-field radiotherapy administered ≤28 days of first dose of AC682
• Major surgery (excluding placement of vascular access) within 4 weeks of first dose of AC682
• Known symptomatic brain metastases requiring the use of steroids
• 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

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. Up to 30 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)		28 days (Cycle 1)
Incidence of treatment-emergent adverse events (TEAEs), and clinically significant grade 3 or higher laboratory abnormalities following administration of AC682	Adverse events will be graded according to NCI CTCAE v5.0.	Through study completion, approximately 18 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Objective response rate (ORR) as a measure of anti-tumor activity	Through study completion, approximately 18 months
Clinical benefit rate (CBR) as a measure of anti-tumor activity	Through study completion, approximately 18 months
Duration of response (DOR) as a measure of anti-tumor activity	Through study completion, approximately 18 months
Disease control rate (DCR) as a measure of anti-tumor activity	Through study completion, approximately 18 months
Progression free survival (PFS) as a measure of anti-tumor activity	Through study completion, approximately 18 months
Pharmacokinetic Analysis: area under the plasma concentration-time curve from time zero extrapolated to infinity (AUC(0-inf))	Through study completion, approximately 18 months
Pharmacokinetic Analysis: area under the concentration-time curve over the dosing interval (AUC(0-tau))	Through study completion, approximately 18 months
Pharmacokinetic Analysis: maximum plasma concentration (Cmax)	Through study completion, approximately 18 months
Pharmacokinetic Analysis: time to maximum plasma concentration (tmax)	Through study completion, approximately 18 months
Pharmacokinetic Analysis: terminal elimination half life (t1/2)	Through study completion, approximately 18 months

Collaborators and Investigators

• Sponsor: Accutar Biotechnology Inc

Study record dates

Study Major Dates

• Study Start (Actual): November 12, 2021
• Primary Completion (Actual): April 4, 2024
• Study Completion (Actual): April 4, 2024

Study Registration Dates

• First Submitted: September 22, 2021
• First Submitted That Met QC Criteria: October 4, 2021
• First Posted (Actual): October 18, 2021

Study Record Updates

• Last Update Posted (Actual): April 11, 2024
• Last Update Submitted That Met QC Criteria: April 9, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Breast cancer; Phase I; HER2 negative; HER2-; 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: AC682-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No