Safety and Efficacy Study of Sapanisertib in Combination With Exemestane or Fulvestrant in Postmenopausal Women With Estrogen Receptor Positive/Human Epidermal Growth Factor Receptor 2 Negative (ER+/HER2-) Metastatic Breast Cancer

This is a phase 1b/2 study of the safety and efficacy of sapanisertib (MLN0128) in combination with exemestane or fulvestrant therapy in women with estrogen receptor positive/human epidermal growth factor receptor 2 negative (ER+/HER2-) advanced or metastatic breast cancer who progressed on treatment with everolimus in combination with exemestane or fulvestrant.

The drug being tested in this study is called sapanisertib (MLN0128). Sapanisertib is being tested in women with estrogen receptor positive/human epidermal growth factor receptor 2 negative (ER+/HER2-) advanced or metastatic breast cancer who progressed on treatment with everolimus. This study will look at the safety and efficacy of sapanisertib when given in combination with exemestane or fulvestrant. The study enrolled 118 patients. This study has two phases: phase 1 and phase 2. Phase 1 has 2 parts. In part 1 of phase 1, unmilled active pharmaceutical ingredient (API) capsules were administered, while in part 2, capsules based on milled API were administered. * Phase 1 (Part 1): sapanisertib 5 mg (unmilled) + exemestane * Phase 1 (Part 1): sapanisertib 5 mg (unmilled) + fulvestrant * Phase 1 (Part 2): sapanisertib 3 mg (milled) + exemestane * Phase 1 (Part 2): sapanisertib 3 mg (milled) + fulvestrant * Phase 1 (Part 2): sapanisertib 4 mg (milled) + exemestane In phase 2, participants were enrolled into one of 2 parallel cohorts, depending on the quality and/or duration of their prior response to everolimus in combination with either exemestane (any country) or fulvestrant (US only). Everolimus-Resistant Cohort: patients who had progressed on treatment with everolimus in combination with either exemestane (any country) or fulvestrant (US only) without achieving an objective response (CR or PR) or after achieving stable disease for \<6 months as their best response. Everolimus-Sensitive Cohort: participants who had progressed on treatment after achieving a CR or PR of any duration, or stable disease for ≥6 months with prior everolimus treatment in combination with either exemestane (any country) or fulvestrant (US only). Participants were to receive MLN0128 in combination with the same dose of the previously administered treatment (exemestane \[any country\] or fulvestrant \[US only\]). This multi-center trial will be conducted worldwide. The overall time to participate in this study was 52 months. Participants made multiple visits to the clinic and were contacted by telephone every 3 months for a follow-up assessment.