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