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

A Phase I/II, Single Arm, Open-label Study of Ribociclib in Combination With Everolimus + Exemestane in the Treatment of Men and Postmenopausal Women With HR+, HER2- Locally Advanced or Metastatic Breast Cancer Following Progression on a CDK 4/6 Inhibitor

The purpose of this study is determine if the triplet combination of ribociclib, everolimus and exemastane is safe and effective in the treatment of locally advanced/metastatic breast cancer following treatment with a CDK 4/6 inhibitor

This trial had two phases. The purpose of Phase I dose escalation and dose de-escalation was to determine the maximum tolerated doses (MTDs) and/or identify the recommended Phase II dose (RP2D) of the combination treatment of ribociclib+ everolimus + exemestane. The dosing was continuous in adult men and postmenopausal women with HR+ HER2-negative advanced breast cancer which was resistant to the non-steroidal aromatase inhibitors, fulvestrant or tamoxifen.

The purpose of the phase II portion of this trial was to evaluate the anti-tumor activity of exemestane, everolimus and ribociclib combination therapy following progression on a CDK 4/6 inhibitor.

The planned duration of the study was 30 months.

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.