A Study To Assess The Tolerability And Clinical Activity Of Gedatolisib In Combination With Palbociclib/Letrozole Or Palbociclib/Fulvestrant In Women With Metastatic Breast Cancer

Inclusion Criteria

• •Women 18 years of age or older, who are either: Postmenopausal or Pre/perimenopausal women with medically-induced menopause by treatment with agents to induce chemical menopause.
• •Histologically or cytologically proven diagnosis of breast cancer with evidence of metastasis.
• •Documentation of estrogen receptor positive ((ER+), human epidermal growth factor receptor 2 (HER2 negative (HER2-)) tumor.
• •Dose Escalation Portion: Patients must satisfy one of the following criteria:
• •* Letrozole combination cohort (L): metastatic breast cancer (MBC) with progression who are candidates for a letrozole-containing regimen, with palbociclib.
• •* Fulvestrant combination cohort (F): MBC with progression who are candidates for a fulvestrant containing regimen, with palbociclib.
• •Dose Expansion Portion: Patients must satisfy one of the following criteria:
• •* Arm A: MBC with progression and no prior endocrine based systemic therapy in the metastatic setting;
• •* Arm B: MBC with progression during or following one prior endocrine based systemic therapy in the metastatic setting, with no prior therapy with any cyclin-dependent kinase (CDK) inhibitor;
• •* Arm C/Arm D: MBC with progression during or following one or two prior endocrine based systemic therapies in the metastatic setting, and following prior therapy with a CDK inhibitor.
• •Measurable disease as defined by Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1.
• •Bone only patients during dose escalation portion.
• •Availability of archival tumor biopsy sample or willing to provide fresh biopsy if not available.
• •Eastern Cooperative Oncology Group \[ECOG\] performance must be 0 or 1.
• •Adequate bone marrow, renal and liver function.