JSKN003 Versus Trastuzumab Emtansine (T-DM1) for HER2-Positive, Advanced Breast Cancer

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.

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.