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

Sponsor

Accutar Biotechnology Inc (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05654532

Collaborator

(none)

Enrollment

Locations

Arm

24.1

Anticipated Duration (Months)

Patients Per Site

1.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer	Drug: AC699	Phase 1

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 Design

Study Type:

Interventional

Anticipated Enrollment :

60 participants

Allocation:

N/A

Intervention Model:

Sequential Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Dec 29, 2022

Anticipated Primary Completion Date :

Jul 31, 2024

Anticipated Study Completion Date :

Dec 31, 2024

Arms and Interventions

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.

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.

Outcome Measures

Primary Outcome Measures

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

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.