This is a study to investigate the potential clinical benefit of G1T38 as an oral therapy in combination with fulvestrant in patients with hormone receptor-positive, HER2-negative metastatic breast cancer.

The study is an open-label design, consists of 2 parts: dose-finding portion (Part 1), and expansion portion (Part 2). Both parts include 3 study phases: Screening Phase, Treatment Phase, and Survival Follow-up Phase. The Treatment Phase begins on the day of first dose with study treatment and completes at the Post-Treatment Visit. Approximately, 102 patients will be enrolled in the study.

Inclusion Criteria:

• Confirmed diagnosis of HR-positive, HER2-negative breast cancer, not amenable to curative therapy

• Pre- or perimenopausal women can be enrolled if amenable to be treated with goserelin

• Patients must satisfy 1 of the following criteria for prior therapy:

  • Progressed during treatment or within 12 months of completion of adjuvant therapy with an aromatase inhibitor or tamoxifen
  • Progressed during treatment or within 2 months after the end of prior aromatase inhibitor therapy for advanced/metastatic breast cancer, or prior endocrine therapy for advanced/metastatic breast cancer
  • Received ≤ 2 chemotherapy regimens (Part 1) or ≤ 1 chemotherapy regimen (Part 2) for advanced/metastatic disease

• For Part 1, evaluable or measurable disease (bone only disease eligible for Part 1 only)

• For Part 2, measurable disease as defined by RECIST, Version 1.1

• ECOG performance status 0 to 1

• Adequate organ function

Exclusion Criteria:

• For Part 1, prior treatment with fulvestrant
• For Part 2, prior treatment with any CDK inhibitor or fulvestrant
• Active uncontrolled/symptomatic CNS metastases, carcinomatous meningitis, or leptomeningeal disease
• Chemotherapy within 21 days of first G1T38 dose
• Investigational drug within 28 days of first G1T38 dose
• Concurrent radiotherapy, radiotherapy within 14 days of first G1T38 dose, previous radiotherapy to the target lesion sites, or prior radiotherapy to > 25% of bone marrow
• Prior hematopoietic stem cell or bone marrow transplantation