a phase ib/ii study to evaluate multiple combination therapies of fwd1802 in patients with er+/her2- bc

Conditions: Metastatic Breast Cancer; Breast Cancer Stage I; Breast Cancer Stage II; Locally Advanced Breast Cancer (LABC); ER+ Breast Cancer

Summary: this is a study to evaluate the efficacy and safety of multiple combination therapies with fwd1802 in subjects with er-positive/her2-negative unresectable locally advanced or metastatic breast cancer


Eligibility criteria:
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