JSKN016 combined with chemotherapy or immunotherapy for inoperable or metastatic HER2-negative breast cancer

The Multicenter, Open-label, Single-arm, Multi-cohort Phase Ib/II Clinical Study to Evaluate the Efficacy and Safety of JSKN016 in Combination Therapy in Chinese Participants With Inoperable Locally Advanced or Metastatic HER2-negative Breast Cancer

This study will test whether adding JSKN016 to chemotherapy or immunotherapy helps people whose HER2-negative breast cancer cannot be removed by surgery or has spread to other parts of the body.

Quick facts

• Phase: PHASE1; PHASE2
• Study type: Interventional
• Enrollment: 180 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Jiangsu Alphamab Biopharmaceuticals Co., Ltd (industry)
• Drugs / interventions: radiation, chemotherapy, immunotherapy, pembrolizumab
• Locations: 1 site (Shanghai)
• Trial ID: NCT06942234 on ClinicalTrials.gov

What this trial studies

This phase 1/2 study enrolls adults with inoperable locally advanced or metastatic HER2-negative breast cancer and assigns them to one of four groups based on hormone receptor status and prior treatments. Each group receives JSKN016 combined with a standard agent — paclitaxel (albumin-bound), capecitabine, eribulin, or pembrolizumab — to determine safe doses and preliminary anti-tumor activity. The primary endpoint is objective response rate (ORR) by RECIST 1.1, with secondary endpoints including safety, duration of response, progression-free survival, and other efficacy measures. Tumor tissue collection and scheduled radiologic assessments are required to support response evaluation and biomarker analyses.

Who should consider this trial

Good fit: Adults aged 18–75 with confirmed inoperable locally advanced or metastatic HER2-negative breast cancer, measurable disease, ECOG performance status 0–1, adequate organ function, and meeting the trial's prior-treatment criteria are the intended participants.

Not a fit: Patients with HER2-positive disease, poor performance status, significant organ dysfunction, inability to provide required tissue samples, or who do not meet the prior-treatment limits are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If effective, the combination could shrink tumors and prolong disease control for patients with advanced HER2-negative breast cancer.

How similar studies have performed: Combinations of chemotherapy with immunotherapy or novel targeted agents have shown benefit in subsets such as triple-negative breast cancer, but JSKN016 itself is investigational with limited prior clinical data.

Eligibility criteria

Inclusion Criteria:

1. Capable of understanding and signing the informed consent form.
2. Aged ≥18 and ≤75 years, regardless of sex.
3. Histologically or cytologically confirmed inoperable locally advanced or metastatic HER2-negative breast cancer.
4. Hormone receptor-positive participants with progression/intolerance after standard endocrine therapy, or unsuitable for it.
5. Disease progression confirmed by radiological evidence post-systemic treatment.
6. Available archived or newly obtained tumor tissue/biopsy.
7. No prior systemic therapy for advanced disease, except for prior endocrine ± targeted therapy or CDK4/6 inhibitors.
8. Measurable non-CNS lesion per RECIST 1.1.
9. Expected survival ≥3 months.
10. ECOG performance status of 0 or 1.
11. Contraceptive use agreement for fertile participants.
12. Adequate organ function within 7 days of enrollment:

    * Bone marrow: ANC ≥1.5 × 10⁹/L, Hemoglobin ≥90 g/L, Platelets ≥100 × 10⁹/L.
    * Liver: Bilirubin ≤1.5 × ULN, ALT/AST ≤3 × ULN.
    * Renal: Creatinine ≤1.5 × ULN or Ccr ≥60 mL/min.
    * Coagulation: INR/PT ≤1.5 × ULN, APTT ≤1.5 × ULN.
13. LVEF ≥50%.

Exclusion Criteria:

1. CNS metastasis (except stable cases treated with radiation or surgery).
2. Unstable spinal cord compression or untreated history.
3. Recent live vaccine (except seasonal flu vaccines).
4. Recent anti-tumor treatment within 28 days or 5 half-lives (whichever is shorter).
5. Recent palliative therapy within 14 days.
6. Major surgery within 28 days or planned during the study.
7. Severe gastrointestinal issues or recent major GI bleeding.
8. Uncontrolled pleural/peritoneal effusions or cachexia.
9. Prior HER3/TROP2-targeted therapy or topoisomerase I inhibitors.
10. Other malignancies within 5 years (except certain skin or localized cancers).
11. Current interstitial lung disease or uncontrolled infections.
12. Severe hypercalcemia or uncontrolled cancer-related pain.
13. Autoimmune diseases, unless stable with treatment.
14. Uncontrolled comorbidities (e.g., active infections, cardiovascular issues).
15. Toxicities from previous treatments not resolved to CTCAE ≤1.
16. Recent steroid use or need for systemic immunosuppressive therapy.
17. Allergy to study drug components.
18. Pregnancy or breastfeeding.

Where this trial is running

Shanghai

• Fudan University Shanghai Cancer center — Shanghai, China (RECRUITING)

Study contacts

• Study coordinator: Jian Zhang

Conditions: Inoperable Locally Advanced HER2-Negative Breast Cancer, Metastatic HER2-Negative Breast Cancer