G1T48, an Oral SERD, Alone and in Combination With Palbociclib in ER-Positive, HER2-Negative Advanced Breast Cancer

Inclusion criteria

• For Part 1, postmenopausal women only
• For Parts 2 and 3, any menopausal status
• Confirmed diagnosis of ER-positive, HER2-negative advanced breast cancer, not amenable to curative therapy
• For Part 1, prior treatment with less than 4 prior lines of chemotherapy
• For Part 2, prior treatment with less than 2 prior line of chemotherapy
• For Part 3, prior treatment with no more than 1 prior line of chemotherapy
• For Parts 1 and 2, prior treatment with less than 4 prior endocrine therapies for metastatic breast cancer
• For Part 3, prior treatment with no more than 1 prior line of endocrine therapies for metastatic breast cancer
• For Parts 1 and 2, 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
• Progressed after the end of prior aromatase inhibitor therapy for advanced/metastatic breast cancer
• For Part 3, patients must satisfy 1 of the following criteria for prior therapy:

• Received ≥ 24 months of endocrine therapy in the adjuvant setting prior to recurrence or progression
• Received ≥ 6 months of endocrine therapy in the advanced/metastatic setting prior to progression
• For Part 1, evaluable or measurable disease
• For Parts 2 and 3, evaluable (approximately 25%) or measurable disease (approximately 75%) as defined by RECIST, Version 1.1 including bone-only disease
• ECOG performance status 0 to 1
• Adequate organ function

Exclusion criteria

• For Part 3, prior treatment with CDK4/6 inhibitor, investigational oral SERDs or SERCAs in any setting
• Active uncontrolled/symptomatic CNS metastases, carcinomatous meningitis, or leptomeningeal disease
• Anticancer therapy within 14 days of first G1T48 dose or within 28 days for antibody-based therapy
• Concurrent radiotherapy, radiotherapy within 14 days of first G1T48 dose, previous radiotherapy to the target lesion sites, or prior radiotherapy to > 25% of bone marrow
• Prior hematopoietic stem cell or bone marrow transplantation