Study of JSKN016 Combination Therapy in Inoperable Locally Advanced 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 aims to evaluate the safety and effectiveness of JSKN016 in combination with different treatments for patients with HER2-negative breast cancer that cannot be removed by surgery or has spread to other parts of the body. The study includes four groups of patients based on treatment history and tumor characteristics. Each group will receive JSKN016 with chemotherapy or immunotherapy. The goal is to find out how well the treatment works and how safe it is.

Study Overview

• Status: Recruiting
• Conditions: Inoperable Locally Advanced HER2-Negative Breast Cancer; Metastatic HER2-Negative Breast Cancer
• Intervention / Treatment: Drug: JSKN016; Drug: Paclitaxel (albumin bound); Drug: Capecitabine; Drug: Eribulin; Drug: Pembrolizumab

Detailed Description

This clinical study investigates the safety and efficacy of JSKN016 combined with various therapies for patients with advanced, inoperable, or metastatic HER2-negative breast cancer. The study includes four groups with different treatment regimens, targeting HR+HER2-negative breast cancer and triple-negative breast cancer (TNBC) with varying prior treatments. Participants will receive JSKN016 in combination with paclitaxel, capecitabine, eribulin, or pembrolizumab. The primary endpoint is the objective response rate (ORR) based on RECIST 1.1 criteria. The secondary endpoints include efficacy, safet, and other related outcomes.

• Study Type: Interventional
• Enrollment (Estimated): 180
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Jian Zhang; Phone Number: +86-21-64175590; Email: syner2000@126.com

Study Locations

• China
  • Shanghai, China
    • Recruiting
    • Fudan University Shanghai Cancer Center
    • Contact: Jian Zhang; Phone Number: +86 18017312990

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1: JSKN016+Paclitaxel; JSKN016 (5mg/kg IV Q3W D1) + nab-paclitaxel (125mg/m² IV Q3W D1, D8)	Drug: JSKN016; JSKN016 is administered via intravenous infusion at doses of 5mg/kg or 6mg/kg every 3 weeks, starting on Day 1 of each cycle. If the 5mg/kg dose is well tolerated during the safety lead-in phase, the dose may be increased to 6mg/kg for subsequent cycles.; Drug: Paclitaxel (albumin bound); The drug is administered intravenously at a dose of 125mg/m², with infusions on Day 1 and Day 8 of each treatment cycle. The treatment cycle is repeated every 3 weeks.
Experimental: Cohort 2: JSKN016+Capecitabine; JSKN016 (5mg/kg IV Q3W D1) + capecitabine (1000mg/m² PO BID Q3W D1-14)	Drug: JSKN016; JSKN016 is administered via intravenous infusion at doses of 5mg/kg or 6mg/kg every 3 weeks, starting on Day 1 of each cycle. If the 5mg/kg dose is well tolerated during the safety lead-in phase, the dose may be increased to 6mg/kg for subsequent cycles.; Drug: Capecitabine; The drug is administered orally at a dose of 1000mg/m², twice daily for two weeks, followed by a one-week break. Treatment cycles repeat every three weeks.
Experimental: Cohort 3: JSKN016+Eribulin; JSKN016 (5mg/kg IV Q3W D1) + eribulin (1.4mg/m² IV Q3W D1, D8)	Drug: JSKN016; JSKN016 is administered via intravenous infusion at doses of 5mg/kg or 6mg/kg every 3 weeks, starting on Day 1 of each cycle. If the 5mg/kg dose is well tolerated during the safety lead-in phase, the dose may be increased to 6mg/kg for subsequent cycles.; Drug: Eribulin; The drug is administered intravenously at a dose of 1.4mg/m², with infusions on Day 1 and Day 8 of each treatment cycle. The treatment cycle is repeated every 3 weeks.
Experimental: Cohort 4: JSKN016+Pembrolizumab/Toripalimab; JSKN016 (5mg/kg IV Q3W D1) + pembrolizumab (200mg IV Q3W D1) or toripalimab (240mg IV Q3W D1).	Drug: JSKN016; JSKN016 is administered via intravenous infusion at doses of 5mg/kg or 6mg/kg every 3 weeks, starting on Day 1 of each cycle. If the 5mg/kg dose is well tolerated during the safety lead-in phase, the dose may be increased to 6mg/kg for subsequent cycles.; Drug: Pembrolizumab; The drug is administered intravenously at a fixed dose of 200mg, with infusions on Day 1 of each 3-week treatment cycle.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objetctive Response Rate (ORR)	The proportion of participants who achieve a confirmed complete response (CR) or partial response (PR), as assessed by investigators according to RECIST v1.1 criteria.	From baseline until disease progression, death, or end of treatment, whichever occurs first (up to approximately 24 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of Response (DoR)	The time from the first documentation of CR or PR to the first documentation of disease progression or death from any cause, whichever occurs first, as assessed by investigators per RECIST v1.1.	From first documented response to progression or death (up to approximately 24 months)
Disease Control Rate (DCR)	The proportion of participants who achieve a best overall response of CR, PR, or stable disease (SD), as assessed by investigators using RECIST v1.1 criteria.	From baseline to disease progression or end of treatment (up to approximately 24 months)
Progression-Free Survival (PFS)	Time from the date of first dose of study drug to the first documentation of disease progression or death from any cause, whichever occurs first, based on investigator assessment using RECIST v1.1.	From first dose until disease progression or death (up to approximately 24 months)
Overall Survival (OS)	Time from the date of first dose of study drug to death from any cause.	From first dose to death (up to approximately 36 months)
Frequency and Severity of Adverse Events (AEs)	Frequency and severity of treatment-emergent adverse events (TEAEs), treatment-related adverse events (TRAEs), serious adverse events (SAEs), and adverse events of special interest (AESIs), coded using MedDRA and graded per NCI-CTCAE v5.0.	From first dose through 30 days after the last dose of study treatment (up to approximately 30 months)

Collaborators and Investigators

• Sponsor: Jiangsu Alphamab Biopharmaceuticals Co., Ltd

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2025
• Primary Completion (Estimated): June 30, 2027
• Study Completion (Estimated): December 31, 2027

Study Registration Dates

• First Submitted: April 10, 2025
• First Submitted That Met QC Criteria: April 16, 2025
• First Posted (Actual): April 24, 2025

Study Record Updates

• Last Update Posted (Estimated): September 17, 2025
• Last Update Submitted That Met QC Criteria: September 11, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Breast Neoplasms; Amino Acids, Peptides, and Proteins; Proteins; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleic Acids, Nucleotides, and Nucleosides; Hydrocarbons; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Terpenes; Taxoids; Cyclodecanes; Diterpenes; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Nucleosides; Uracil; Pyrimidinones; Deoxyribonucleosides; Fluorouracil; Albumins; Paclitaxel; Capecitabine; Albumin-Bound Paclitaxel; pembrolizumab; eribulin
• Other Study ID Numbers: JSKN016-202

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No