Study of AC699 in Patients With Estrogen Receptor Positive/Human Epidermal Growth Factor Receptor 2 Negative (ER+/HER2-) Locally Advanced or Metastatic Breast Cancer

A Phase I Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Preliminary Anti-Tumor Activity of AC699 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 AC699 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 AC699 that can be given safely to participants
• Evaluate the safety profile of AC699
• Evaluate the pharmacokinetics of AC699
• Evaluate the effectiveness of AC699

Study Overview

• Status: Active, not recruiting
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: AC699

Detailed Description

This study is a Phase I, first-in-human, open-label dose-escalation study of AC699, an orally bioavailable estrogen receptor degrader, given as a single agent.

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Colorado
    • Denver, Colorado, United States, 80218
      • Site 08
  • Florida
    • Orlando, Florida, United States, 32746
      • Site 07
    • Sarasota, Florida, United States, 34232
      • Site 02
  • Maryland
    • Rockville, Maryland, United States, 21044
      • Site 06
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Site 01
  • Texas
    • Houston, Texas, United States, 77030
      • Site 03
    • San Antonio, Texas, United States, 78240
      • Site 09
  • Virginia
    • Norfolk, Virginia, United States, 23502
      • Site 05
  • Washington
    • Vancouver, Washington, United States, 98684
      • Site 04

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Signed written informed consent (ICF)
• Adult male and female participants, at least 18 years-of-age at the time of signature of the ICF
• Female participants must be postmenopausal
• Confirmed diagnosis of advanced, unresectable, and/or metastatic breast cancer following disease progression on standard treatment, or for whom no therapy of proven efficacy exists, or who are not amenable to standard therapies
• Histologically and/or cytologically confirmed diagnosis of estrogen-receptor positive (ER+) human epidermal growth factor 2 negative (HER2-) breast cancer
• Must have received at least 2 prior endocrine or at least 1 prior line of endocrine therapy if combined with CDK4/6 inhibitor
• Prior chemotherapy is not required, but up to 3 prior regimens of cytotoxic chemotherapy will be allowed in the locally advanced/ metastatic setting
• At least 1 measurable lesion according to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 (Appendix B) or at least 1 predominantly lytic bone lesion in the absence of measurable disease
• Acceptable organ and hematologic function at baseline
• Life expectancy ≥12 weeks after the start of the treatment

Exclusion Criteria:

• Treatment with any of the following:

  • Any cytotoxic chemotherapy, investigational agents or other anti-cancer drugs for the treatment of locally advanced or metastatic breast cancer within 14 days prior to the first administration of AC699
  • Radiation therapy within 14 days prior to first study drug administration that did not resolve to tolerable toxicity, or prior irradiation to >25% of bone marrow. Prior palliative radiotherapy to metastatic lesion(s) is permitted, provided it has been completed 7 days prior to study enrollment and no clinically significant toxicities are expected (e.g., mucositis, esophagitis).
  • Major surgery within 21 days prior to the first study drug administration (exception: participants may enroll if fully recovered or without intolerable or clinically significant adverse effects but at least 14 days must have elapsed between major surgery and first study drug administration)
• Known symptomatic brain metastases requiring the use of systemic corticosteroids ≥10 mg/day prednisone or equivalents. Asymptomatic and treated, or asymptomatic untreated brain metastases are allowed as long as participants are clinically stable. Stable doses of anticonvulsants are allowed.
• Any condition that impairs a participant'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 AC699.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: AC699 Dose Escalation; Participants will receive an assigned dose of AC699 monotherapy during dose escalation. One cycle is defined as 28 days.	Drug: AC699; Participants will receive AC699 orally daily in 28-day cycles.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Incidence of dose limiting toxicities (DLTs) from AC699 monotherapy	First 28 days of treatment. Cycles are 28 days.
Incidence of treatment-emergent adverse events (TEAEs) and clinically significant Grade 3 or higher lab abnormalities following administration of AC699	Approximately 18 months.

Secondary Outcome Measures

Outcome Measure	Time Frame
Objective response rate (ORR) to assess the anti-tumor activity of AC699	Approximately 18 months.
Clinical Benefit Rate (CBR) to assess the anti-tumor activity of AC699 using RECIST 1.1	Approximately 18 months.
Duration of Response (DOR) to assess the anti-tumor activity of AC699 using RECIST 1.1	Approximately 18 months.
Disease Control Rate (DCR) to assess the anti-tumor activity of AC699 using RECIST 1.1	Approximately 18 months.
Progression Free Survival (PFS) to assess the anti-tumor activity of AC699 using RECIST 1.1	Approximately 18 months.
Pharmacokinetic Analysis: Area under the concentration-time curve over the dosing interval (AUC(0-infinity))	Up to approximately 28 weeks
Pharmacokinetic Analysis: Area under the concentration-time curve over the dosing interval (AUC(0-tau))	Up to approximately 28 weeks
Pharmacokinetic Analysis: Maximum plasma concentration (Cmax)	Up to approximately 28 weeks
Pharmacokinetic Analysis: Time to maximum plasma concentration (tmax)	Up to approximately 28 weeks
Pharmacokinetic Analysis: Terminal elimination half-life (t1/2)	Up to approximately 28 weeks

Collaborators and Investigators

• Sponsor: Accutar Biotechnology Inc

Study record dates

Study Major Dates

• Study Start (Actual): December 29, 2022
• Primary Completion (Estimated): March 31, 2026
• Study Completion (Estimated): May 31, 2026

Study Registration Dates

• First Submitted: December 8, 2022
• First Submitted That Met QC Criteria: December 8, 2022
• First Posted (Actual): December 16, 2022

Study Record Updates

• Last Update Posted (Estimated): September 30, 2025
• Last Update Submitted That Met QC Criteria: September 25, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: Breast Cancer; Metastatic breast cancer; HER2-; MBC; ER positive; ER+; Human epidermal growth factor receptor 2 negative; Locally advanced breast cancer; HER2 negative breast cancer; ER degrader; Estrogen receptor-positive breast cancer; AC699; ER chimeric degrader
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Skin and Connective Tissue Diseases; Breast Neoplasms
• Other Study ID Numbers: AC699-001

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