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

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.

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.