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

Study Overview
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Brief Summary
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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 400 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

Detailed Description
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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 400 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.

Official Title
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A Phase 3, Multicenter, Randomized, Open-Label, Active-Controlled Trial Of JSKN003 Versus Treatment Of Physician'S Choice For HER2-low, Unresectable and/or Metastatic Breast Cancer Subjects

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: JSKN003
* Drug: Capecitabine tablets
* Drug: Gemcitabine hydrochloride for injection
* Drug: Vinorelbine tartrate injection
* Drug: Paclitaxel for injection (albumin-bound type)
* Drug: Docetaxel injection
* Drug: Eribulin mesylate injection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 1. The subject is able to understand the informed consent form, voluntarily participate and sign the informed consent form. 2. The subject ≥ 18 years old on the day of signing the informed consent form, male or female. 3. 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+. 4. Have received at least 1 to 2 lines of chemotherapy regimens for breast cancer in the relapse/metastatic stage. 5. Willing to provide sufficient archived tumor pathology specimens for central laboratory detection of HER2 status. 6. Documented radiographic disease progression (during or after the most recent treatment). 7. At least one extracranial measurable lesion at baseline according to RECIST 1.1 criteria. 8. 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. 11. Laboratory tests within 14 days before administration and cardiac function tests within 28 days meet the criteria. 12. Have sufficient elution of previous treatment before administration. Exclusion Criteria: 1. Untreated, or unstable brain parenchymal metastases, spinal cord metastases or compression, cancerous meningitis. 2. Patients with only skin lesions as target lesions. 3. Those with a history of other primary malignant tumors within 5 years before administration. 4. Selection of the control drug by the investigator who is not suitable for the protocol prescribed. 5. Previous use of anti-HER2 therapeutics, including anti-HER2 antibody conjugates. 6. Previous use of antibody conjugates containing topoisomerase I inhibitors. 7. There is a third gap fluid that cannot be controlled by drainage, etc. 8. Previous or current interstitial pneumonia/lung disease requiring systemic hormone therapy. 9. Inability to swallow, chronic diarrhea, intestinal obstruction, or other factors that affect oral administration and absorption of the drug. 10. Previous or current autoimmune disease. 11. Have uncontrolled comorbidities. 12. The toxicity of previous antitumor therapy has not been restored to grade ≤1 (NCI-CTCAE v5.0). 13. History of previous immunodeficiency. 14. History of life-threatening allergic reactions or known ≥ grade 3 allergy to any component or excipient in the investigational pharmaceutical formulation. 15. 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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: A Phase 3, Multicenter, Randomized, Open-Label, Active-Controlled Trial
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: JSKN003<br>Administered intravenously according to protocol. | Drug: JSKN003<br>* Administered intravenously according to protocol.<br>|
| Active Comparator: The chemotherapy chosen by the investigator<br>The mono-chemotherapy drugs selected by the investigators included capecitabine, gemcitabine, vinorelbine, docetaxel, albumin-bound paclitaxel, or eribulin. The option should be determined before randomization. | Drug: Capecitabine tablets<br>* Administered according to protocol, as one option for investigator's choice (determined before randomization).<br>Drug: Gemcitabine hydrochloride for injection<br>* Administered according to protocol, as one option for investigator's choice (determined before randomization).<br>Drug: Vinorelbine tartrate injection<br>* Administered according to protocol, as one option for investigator's choice (determined before randomization).<br>Drug: Paclitaxel for injection (albumin-bound type)<br>* Administered according to protocol, as one option for investigator's choice (determined before randomization).<br>Drug: Docetaxel injection<br>* Administered according to protocol, as one option for investigator's choice (determined before randomization).<br>Drug: Eribulin mesylate injection<br>* Administered according to protocol, as one option for investigator's choice (determined before randomization).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival (PFS) | PFS evaluated by BICR according to RECIST v1.1 criteria is defined as the time from randomization to the first recorded disease progression or death from any cause as a result of BICR evaluation according to RECIST v1.1 criteria. | 16 months 、26 months after the first enrollment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival（OS） | OS, defined as the time from randomization to death from any cause; | 16 months 、26months 、60 months after the first enrollment | 
| Objective Response Rate (ORR) | BICR and investigators were judged according to RECIST v1.1 criteria ，objective response rate (ORR), defined as the proportion of participants achieving a complete response (CR) or partial response (PR) according to RECIST v1.1 criteria; | 16 months 、26 months after the first enrollment | 
| Duration of Response (DOR) | BICR and investigators were judged according to RECIST v1.1 criteria，Duration of response (DoR), defined as the time from the first recorded response (CR/PR) to the first documented disease progression (PD) or death from any cause; | 16 months 、26 months after the first enrollment |