jskn003 versus trastuzumab emtansine (t-dm1) for her2-positive, advanced breast cancer

Conditions: Unrespectable Locally Advanced and or Metastatic HER2 Positive Breast Cancer Participants

Summary: this study is designed to compare the safety and efficacy of jskn003 versus t-dm1 in unrespectable locally advanced and/or metastatic her2-positive breast cancer participants previously treated with trastuzumab and taxane.

this is a randomized, controlled, open-label, multicenter, phase 3 clinical study to compare the efficacy and safety of jskn003 versus t-dm1 in unresectable locally advanced and/or metastatic her2-positive breast cancer participants previously treated with trastuzumab and taxane. participants will be treated with jskn003 at 6.3 mg/kg or trastuzumab emtansine at 3.6 mg/kg every 3 weeks (q3w). participants will continue to receive treatment until disease progression, intolerable toxicity, withdrawal of informed consent, death, or any other reasons for treatment discontinuation, whichever occurs first.

Eligibility criteria:
inclusion criteria: * 1. voluntarily agree to participate in the study and sign the informed consent. * 2.age≥18 years old. * 3.patients with unresectable locally advanced or metastatic breast cancer confirmed by histology or cytology. * 4.confirmed to be her2 positive (her2-positive is defined as ihc 3+ or ihc 2+ with ish positive) by the pathology department of participating study center. * 5.have received treatment regimen including trastuzumab (allowed marketed trastuzumab biosimilars) or inetetamab with radiologic or pathologic progression/ relapse during the advanced stage, during neoadjuvant or adjuvant therapy, or within 12 months after treatment. * 6.previously treated with taxanes. * 7.had radiologic and/or pathologic progression or intolerance of the latest systemic anti-tumor therapy. * 8.at least one extracranial measurable lesion at baseline according to recist 1.1 criteria. * 9.ecog ps of 0 - 1. * 10.patients with adequate organ and bone marrow functions. * 11.expected survival ≥ 3 months. * 12.female and male patients of childbearing age agree to take adequate contraceptive measures during and upon completion of the study for 7 months after the last dose of jskn003 or t-dm1. exclusion criteria: * 1. have previously been treated with an anti-her2 adc loaded with topoisomerase i inhibitors or medenosin derivative 1 (dm1) or have relapsed after receiving such therapy during or within 12 months after the adjuvant/neo-adjuvant setting or in the advanced stage. * 2.history of any other malignant tumors within three years before randomization. * 3.with uncontrollable serous effusion within 14 days before randomization, which requires frequent drainage or medical intervention. * 4.known contraindication to t-dm1or not suitable to receive jskn003 or t-dm1 by investigator. * 5.has not recovered from adverse reactions caused by previous anti-tumor treatments to ≤ grade 1 (refer to nci ctcae 5.0) or baseline (excluding grade 2 alopecia, hyperpigmentation, simple laboratory test abnormalities, and other toxicity for a non-safety risk by investigators). * 6.received immunotherapy, macromolecular targeted therapy or other anti-tumor biological therapy within 4 weeks before randomization, or received palliative radiotherapy, endocrine therapy, cytotoxic drug chemotherapy and small molecular targeted drug therapy within 2 weeks before randomization, or received traditional chinese medicine preparations with anti-tumor indications within 2 weeks before randomization. * 7.major organ surgery within 28 days before randomization. * 8.untreated (including baseline findings) or unstable cerebral parenchymal metastasis, spinal cord metastasis or compression, and cancerous meningitis. * 9.the cumulative amount of previous exposure to anthracyclines has reached the pre-specified dosage. * 10.history of lvef \< 40% during prior anti-her2 drug therapy or symptomatic congestive heart failure (chf). * 11.serious or uncontrolled cardiovascular disease. * 12.history of (non-infectious) interstitial lung disease/pneumonitis requiring therapy or grade ≥3 interstitial lung disease/ pneumonitis during previous anti-tumor treatments. * 13.active infections requiring intravenous antibiotics, antivirals, or antifungals within 14 days before randomization. * 14. active hepatitis b or hepatitis c. * 15.history of immunodeficiency or hiv antibody test positive at screening. * 16.received a potent inhibitor of cyp3a4 within 14 days prior to randomization or during study treatment. * 17.pregnant or nursing females; * 18.other reasons enrolled in this clinical trial as considered unsuitable by the investigator.