For Cohort E only: prior treatment with fulvestrant is prohibited
Fulvestrant within 30 days prior to first dose of study drug.
For Part G (abemaciclib + LY3023414 + fulvestrant): The participant may have received prior systemic endocrine therapy with at least one nonsteroidal aromatase inhibitor (anastrozole, letrozole) for metastatic disease.
Cohort 5: Prior treatment with fulvestrant; Prior treatment with chemotherapy for advanced/metastatic disease; Any line(s) of therapy following treatment failure with a CDK 4/6 inhibitor in combination with an AI; Prior treatment with chemotherapy in the advanced/metastatic setting or with fulvestrant; Advanced/metastatic disease that is symptomatic and/or with visceral spread
Fulvestrant combination cohort (F): MBC with progression who are candidates for a fulvestrant containing regimen, with palbociclib.
Prior selective estrogen receptor downregulator use (SERD), including fulvestrant
Candidate for fulvestrant therapy – patients who have started fulvestrant may enter this trial if within 3 months of starting fulvestrant
Known abnormalities in coagulation such as bleeding diathesis, or treatment with anticoagulants precluding intramuscular injections of fulvestrant or goserelin (if applicable)
Any condition contraindicating fulvestrant administration:
Patients must have been treated with fulvestrant for at least 56 days as their most current anti-cancer treatment, and they must be tolerating fulvestrant with at most grade I toxicity by Common Terminology Criteria for Adverse Events (CTCAE) v4.0
Known abnormalities in coagulation such as bleeding diathesis, or treatment with anticoagulants precluding intramuscular injections of fulvestrant or goserelin (if applicable).
patient has known hypersensitivity to alpelisib, fulvestrant or letrozole
ADDITIONAL INCLUSION CRITERIA FOR PATIENTS IN COMBINATION FULVESTRANT/CABOZANTINIB COHORT
ADDITIONAL EXCLUSION CRITERIA FOR PATIENTS IN COMBINATION FULVESTRANT/CABOZANTINIB COHORT
Subject has had prior progression on treatment with fulvestrant (prior adjuvant treatment or brief exposure in the advanced setting is allowed)
may have received any endocrine therapy (excluding fulvestrant)
At least 6 months must have elapsed from the use of fulvestrant
Inclusion Criteria:\n\n        Phase 1a portion\n\n          -  Histologically or cytologically proven diagnosis of adenocarcinoma of the breast with\n             evidence of either locally recurrent disease not amenable to resection or radiation\n             therapy with curative intent, or metastatic disease, both progressing after at least 6\n             months of hormonal therapy for estrogen receptor (ER) positive breast cancer\n\n          -  ER-positive, human epidermal growth factor 2 (HER2) negative\n\n          -  At least 2 months must have elapsed from the use of tamoxifen\n\n          -  At least 6 months must have elapsed from the use of fulvestrant\n\n          -  At least 2 weeks must have elapsed from the use of any other anticancer hormonal\n             therapy\n\n          -  At least 3 weeks must have elapsed from the use of any chemotherapy\n\n          -  Postmenopausal status\n\n          -  Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 2\n\n          -  Adequate organ function\n\n        Phase Ib portion\n\n          -  All above inclusion criteria, except:\n\n          -  Postmenopausal status, pre- and peri-menopausal participants will also be included\n\n          -  ECOG performance status less than 2\n\n          -  At least 2 months must have elapsed from the use of tamoxifen not applicable\n\n          -  At least 6 months must have elapsed from the use of fulvestrant not applicable\n\n        and plus:\n\n          -  Documented sensitivity to prior hormonal therapy\n\n          -  Cohort C1 (palbociclib combination cohorts): no prior treatment with cyclin-dependent\n             kinase (CDK) 4/6 inhibitor\n\n        Phase IIa portion\n\n          -  All above inclusion criteria for Phase Ia, except:\n\n          -  Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1\n\n          -  At least 6 months must have elapsed from the use of fulvestrant not applicable\n\n        and plus:\n\n          -  Cohort A only: confirmed estrogen receptor alpha (ESR1) mutation and presence of\n             measurable disease as per RECIST v1.1 or evaluable bone disease\n\n          -  Cohort A1 only: no prior fulvestrant allowed; at least 2 months must have elapsed from\n             the use of tamoxifen\n\n          -  Cohort A2 only: prior fulvestrant allowed\n\n          -  Cohort B only: disease progression following no more than 1 prior treatment with an\n             aromatase inhibitor in the advanced/metastatic setting\n\n          -  Cohort B1 only: no prior fulvestrant allowed\n\n          -  Cohort B2 only: prior fulvestrant allowed\n\n        Exclusion Criteria:\n\n        Phase 1a portion\n\n          -  Untreated or symptomatic central nervous system (CNS) metastases\n\n          -  Endometrial disorders\n\n          -  More than 2 prior chemotherapy in the advanced/metastatic setting (prior adjuvant\n             chemotherapy is allowed so long as it occurred greater than or equal to 12 months\n             prior to enrollment)\n\n          -  Current treatment with any systemic anticancer therapies for advanced disease\n\n          -  Any significant cardiac dysfunction within 12 months prior to enrollment\n\n          -  Active inflammatory bowel disease or chronic diarrhea, short bowel syndrome, or upper\n             gastrointestinal surgery including gastric resection\n\n          -  Known human immunodeficiency virus (HIV) infection\n\n          -  Known clinically significant history of liver disease\n\n          -  Major surgery within 4 weeks prior to enrollment\n\n          -  Radiation therapy within 2 weeks prior to enrollment\n\n        Phase Ib portion - all above exclusion criteria, plus:\n\n          -  Cohort C1 (palbociclib combination cohorts): history of venous thromboembolic event\n             requiring therapeutic anticoagulation; vaginal bleeding within 2 months prior to\n             enrollment\n\n        Phase IIa portion - all above exclusion criteria, plus:\n\n          -  Cohort A1, A2, and Cohort B2 only: more than 1 prior chemotherapy in the\n             advanced/metastatic setting\n\n          -  Cohort B1 only: prior chemotherapy in the advanced/metastatic setting
Participants for whom endocrine therapy (example [e.g.], fulvestrant) is recommended and treatment with cytotoxic chemotherapy is not indicated at time of entry into the study
Prior treatment with fulvestrant
Part A, B and C: Fulvestrant therapy less than 90 days before first dose of study treatment. Part D: Fulvestrant therapy less than 42 days before first dose of study treatment
Therapeutic-dose anticoagulation must be discontinued and coagulation parameters must be normalized prior to the first dose of GSK525762 and fulvestrant.
Prior treatment with fulvestrant
Subject has received prior treatment with fulvestrant.
Prior treatment with eribulin, fulvestrant or anastrozole, paclitaxel, abraxane, docetaxel, vinorelbine, or capecitabine
Participants who have received previous therapy with neratinib or fulvestrant
Prior treatment with fulvestrant
Patients who have received other agents that modulate or downregulate the estrogen receptor (e.g. raloxifene, fulvestrant) in the locally advanced or metastatic setting are eligible if they were on treatment for at least 6 months and must have discontinued these agents 6 months prior to study registration
Disease refractory to either, AI, tamoxifen or fulvestrant
Patients in the combination arms - known hypersensitivity to fulvestrant
patient had been permanently discontinued from oral dovitinib study treatment, either alone or in combination with fulvestrant, in the parent study
Received one prior cycle of fulvestrant within 28 days of randomization are eligible.
?2 prior doses of fulvestrant are not eligible
Hyper sensitivity to fulvestrant treatment excipients
Previous treatment with fulvestrant
As per national or local treatment guidelines, endocrine therapy (i.e., fulvestrant) is recommended and treatment with cytotoxic chemotherapy is not necessary for participants, at time of entry into the study.
They have progressed on at least one previous line of endocrine therapy (ET) for\n                  their metastatic disease (but are not currently progressing on fulvestrant), OR;
Patients who are progressing on current fulvestrant therapy (patients who have had\n             fulvestrant therapy in the past and were subsequently treated with other therapies or\n             those who are starting fulvestrant as their next line of ET are eligible for the\n             study).