New hope for advanced breast cancer: combination therapy trial launches

Copied word for word from the study's registry entry, so the wording is the study team's rather than ours.

Inclusion Criteria: * Subjects consent to provide blood samples for centralized laboratory testing of ESR1 mutation status and other biomarkers. * Histologically or cytologically confirmed ER-positive/HER2-negative locally advanced or metastatic breast cancer * Subjects must meet at least one of the following criteria: postmenopausal or prior bilateral oophorectomy, or postmenopausal or Premenopausal/perimenopausal women must agree to receive and maintain approved luteinizing hormone-releasing hormone (LHRH) agonist therapy during study treatment * Prior Therapy Requirements:Subjects must meet all of the following criteria: 1. Progression during/after, intolerance to, ineligibility for, or refusal of standard therapy 2. Endocrine therapy history: Recurrence during or within 1 year after completing ≥2 years of adjuvant endocrine therapy;OR progression after ≥1 line of endocrine therapy for advanced breast cancer(ABC) with ≥6 months of maintenance therapy (no restriction on the number of prior endocrine therapy lines). 3. ≤2 prior lines of chemotherapy for ABC 4. No prior SERD (selective estrogen receptor degrader) therapy except fulvestrant 5. Everolimus combination arm: Prior CDK4/6 inhibitor therapy requiredf) CDK4/6 inhibitor combination arm:Permitted ≤1 line of prior non-investigational CDK4/6 inhibitor therapy;If only received adjuvant CDK4/6 inhibitor therapy, recurrence must occur \>12 months after treatment completion Note: Antibody-drug conjugates (ADCs) are classified as chemotherapy in this study. * Phase Ib: At least one evaluable lesion per RECIST v1.1, allowed subjects with osteolytic bone lesion(s) confirmed by CT/MRI.Phase II: At least one measurable lesion per RECIST v1.1. Subject must have sufficient organ and bone marrow functions at screening. Exclusion Criteria: * Leptomeningeal metastasis (carcinomatous meningitis)；Spinal cord compression；Symptomatic or clinically unstable central nervous system (CNS) metastases； * History or any persistent chronic gastrointestinal disorders or other conditions of impaired absorption that may interfere with oral absorption of the investigational drug * Symptomatic visceral metastases , or clinically symptomatic and unstable effusions;Pleural effusion;Ascites;Pericardial effusion or Pulmonary lymphangitis carcinomatosa. Prior intracavitary infusion therapy should have more than 14 days of stabilization, * Prior therapy with any selective estrogen receptor degrader (SERD) or similar agents other than fulvestrant * Inadequate washout period for prior anticancer therapies. * Type 1 diabetes mellitus; Type 2 diabetes mellitus with poor glycemic control at screening(applies only to the everolimus combination arm). * Subjects will be excluded if they meet any of the following: 1. Interstitial lung disease or drug-induced ILD history, OR evidence of active pneumonitis on chest CT scan within 4 weeks prior to first study treatment. 2. Severe pulmonary disease at screening, including but not limited to:Severe asthma;Severe chronic obstructive pulmonary disease (COPD) Idiopathic * Uncontrolled hypertension despite antihypertensive therapy, defined as:Systolic blood pressure (SBP) \>150 mmHg OR Diastolic blood pressure (DBP) \>95 mmHg. * Active cardiac disease or history of cardiac dysfunction