Study of Ribociclib With Everolimus + Exemestane in HR+ HER2- Locally Advanced/Metastatic Breast Cancer Post Progression on CDK 4/6 Inhibitor.

The purpose of the phase I dose escalation part of this study is to estimate the MTD(s)
and/or identify the RP2D of the combination treatment of ribociclib+ everolimus + exemestane
when dosed continuously in adult men and postmenopausal women with HR+ HER2-negative advanced
breast cancer resistant to the non-steroidal aromatase inhibitors, fulvestrant or tamoxifen.

The purpose of the phase II portion of this trial will be to evaluate the anti-tumor activity
of exemestane, everolimus and ribociclib triplet following progression on a CDK 4/6
inhibitor. This part of the study will be conducted using a Simon's optimal two-stage design.

Inclusion Criteria:

- Adult men and women

- Patient has a confirmed diagnosis of estrogen-receptor positive and/or progesterone
receptor positive breast cancer by local laboratory and has HER2-negative breast
cancer

- Patient must have either measurable disease by RECIST 1.1 or bone lesions in absence
of measurable disease.

- ECOG Performance Status 0 - 1

- Disease refractory to either, AI, tamoxifen or fulvestrant

- Previously treated on any CDK 4/6 inhibitor.

- Patient has adequate bone marrow and organ function.

Exclusion Criteria:

- Patient with symptomatic visceral disease or any disease burden that makes the patient
ineligible for endocrine therapy per the investigator's best judgment.

- Patient has received more than one line of chemotherapy for advanced disease.

- Previous treatment with mTOR inhibitors, or exemestane for advanced disease.

- Progressed on more than one CDK 4/6 inhibitor

- Patient with CNS involvement unless they are at least 4 weeks from prior therapy
completion.

- Clinically significant, uncontrolled heart disease and/or recent cardiac events.