JSKN003 Versus Treatment Of Physician'S Choice For HER2-low, Unresectable and/or Metastatic Breast Cancer Subjects

This study is a randomized controlled, open-label, multicenter phase III clinical study evaluating the efficacy and safety of chemotherapy selected by investigator JSKN003 s in subjects with recurrent or metastatic breast cancer who have previously failed first- or second-line chemotherapy in subjects with recurrent or metastatic breast cancer who have failed prior first- or second-line chemotherapy.

The study planned to enroll 408 subjects in a 1:1 ratio and stratified block randomization method assigned to:

• Experimental group: JSKN003 monotherapy
• Control group: investigator's chosen chemotherapy drug (capecitabine, gemcitabine, vinorelbine, docetaxel, albumin-bound paclitaxel, or eribulin) monotherapy.

Inclusion criteria

• 1. The subject is able to understand the informed consent form, voluntarily participate and sign the informed consent form.

• The subject ≥ 18 years old on the day of signing the informed consent form, male or female.

• Unresectable locally recurrent or metastatic breast cancer, previous histopathological reports of HER2 IHC 1+ or 2+ and ISH-, previous histopathological reports have not been diagnosed as HER2 IHC 3+ or 2+ and ISH+.

• Have received at least 1 to 2 lines of chemotherapy regimens for breast cancer in the relapse/metastatic stage.

• Willing to provide sufficient archived tumor pathology specimens for central laboratory detection of HER2 status.

• Documented radiographic disease progression (during or after the most recent treatment).

• At least one extracranial measurable lesion at baseline according to RECIST 1.1 criteria.

• Expected survival ≥ 3 months. 9. ECOG score of 0 or 1 within 14 days prior to administration. 10. Female subjects of childbearing potential or male subjects of fertile partner consent to use highly effective contraception from the signing of informed consent.

• Laboratory tests within 14 days before administration and cardiac function tests within 28 days meet the criteria.

• Have sufficient elution of previous treatment before administration.

Exclusion criteria

• 1. Untreated, or unstable brain parenchymal metastases, spinal cord metastases or compression, cancerous meningitis.

• Patients with only skin lesions as target lesions. 3. Those with a history of other primary malignant tumors within 5 years before administration.

• Selection of the control drug by the investigator who is not suitable for the protocol prescribed.

• Previous use of antibody conjugates containing topoisomerase I inhibitors. 6. There is a third gap fluid that cannot be controlled by drainage, etc. 7. Previous or current interstitial pneumonia/lung disease requiring systemic hormone therapy.

• Inability to swallow, chronic diarrhea, intestinal obstruction, or other factors that affect oral administration and absorption of the drug.

• Previous or current autoimmune disease. 10. Have uncontrolled comorbidities. 11. The toxicity of previous antitumor therapy has not been restored to grade ≤1 (NCI-CTCAE v5.0).

• History of previous immunodeficiency. 13. History of life-threatening allergic reactions or known ≥ grade 3 allergy to any component or excipient in the investigational pharmaceutical formulation.

• Other conditions that the investigators believe will affect the safety or adherence to drug treatment in this study, including but not limited to psychiatric disorders, alcohol or drug abuse.