A Study of JSKN003 Versus Trastuzumab in Combination With Pertuzumab and Docetaxel as First-Line Treatment for HER2-Positive Recurrent or Metastatic Breast Cancer

NCT07545044 | Not Yet Recruiting Phase 2

• 1 other identifier: JSKN003-008
• Study Type: interventional
• Target: 60
• Locations: 0 countries
• Sites: N/A

Brief Summary

This study is a randomized, controlled, open-label, multicenter, phase II superiority clinical trial. The planned study population consists of participants with HER2-positive recurrent or metastatic breast cancer who have not previously received systemic therapy for advanced disease (participants who have undergone one prior endocrine treatment regimen are eligible for enrollment). The study aims to compare the efficacy and safety of JSKN003 versus trastuzumab combined with pertuzumab and docetaxel as first-line treatment for participants with HER2-positive recurrent or metastatic breast cancer.

Conditions

HER2-positive Recurrent or Metastatic Breast Cancer

Keywords

breast cancer, HER2-positive, first-line treatment

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate (ORR)

  ORR as Assessed by Investigator according to RECIST v1.1.

  Up to 2 years

Secondary Outcomes (6)

• Progression-Free Survival (PFS)

  Up to 2 years

• Disease Control Rate (DCR)

  Up to 2 years

• Duration of Response (DoR)

  Up to 2 years

• Adverse Event (AE)

  Up to 2 years

• Plasma concentrations of JSKN003, total antibodies, and free toxin

  Up to 2 years

Study Arms (2)

Experimental group

EXPERIMENTAL

JSKN003

Drug: JSKN003

Control group

ACTIVE COMPARATOR

Trastuzumab + Pertuzumab + Docetaxel

Drug: Trastuzumab; Drug: Pertuzumab; Drug: Docetaxel

Interventions

JSKN003 DRUG

6.3 mg/kg, IV, D1, Q3W

Experimental group

Trastuzumab DRUG

8mg/kg loading dose, then 6mg/kg, IV, D1, Q3W

Control group

Pertuzumab DRUG

840mg loading dose, then 420mg, IV, D1, Q3W

Control group

Docetaxel DRUG

75 mg/m2, IV, D1, Q3W for minimum of 6 cycles or until intolerable toxicity\[ym1.1\]\[z1.2\] or disease progression, whichever occurs first.

Control group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Voluntary participation in this study and signing of the informed consent form (ICF).
• Age ≥ 18 years.
• Histologically and/or cytologically confirmed recurrent or metastatic breast cancer.
• HER2-positive tumor status confirmed by the central laboratory (Positive definition: IHC 3+, or IHC 2+ with positive ISH).
• No prior systemic chemotherapy and/or HER2-targeted therapy for recurrent or metastatic disease. Participants who have received one prior endocrine therapy regimen are eligible. Participants who experienced recurrence more than 12 months after completing (neo)adjuvant HER2-targeted therapy may be considered for enrollment.
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1.
• Presence of at least one measurable lesion per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
• Adequate organ and bone marrow function (without transfusion or use of hematopoietic growth factors for correction within 14 days prior to testing):
• Absolute neutrophil count (ANC) ≥ 1.5 × 10⁹/L, Platelet count ≥ 100 × 10⁹/L, Hemoglobin ≥ 90 g/L.
• Hepatic function: Total bilirubin (TBIL) ≤ 1.0 × upper limit of normal (ULN); alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × ULN (≤ 5 × ULN for participants with liver metastases); alkaline phosphatase (ALP) ≤ 2.5 × ULN.
• Renal function: Creatinine clearance ≥ 50 mL/min (calculated using the Cockcroft-Gault formula).
• Coagulation function: International normalized ratio (INR) ≤ 1.5 and activated partial thromboplastin time (APTT) ≤ 1.5 × ULN. For participants receiving anticoagulant therapy, the investigator must deem both INR and APTT to be within a safe and effective therapeutic range.
• Left ventricular ejection fraction (LVEF) \> 50%.
• Life expectancy ≥ 3 months.
• For female participants of childbearing potential, a negative serum pregnancy test result must be obtained within 7 days prior to randomization. Participants of childbearing potential or those with partners of childbearing potential must agree to use reliable and effective methods of contraception during the study treatment period and for at least 7 months after the last dose of study treatment.

You may not qualify if:

• Contraindications to trastuzumab, pertuzumab, and docetaxel, or deemed by the investigator as unsuitable for treatment with JSKN003.
• Prior treatment with antibody-drug conjugates containing a topoisomerase I inhibitor (e.g., DS-8201, SHR-A1811, TQB-2102, etc.).
• Toxicities from prior anti-tumor therapy have not recovered to ≤ Grade 1 per CTCAE 6.0 (except for toxicities judged by the investigator to pose no safety risk, such as alopecia, peripheral neuropathy, or isolated laboratory abnormalities, which must have resolved to ≤ Grade 2).
• During prior anti-HER2 therapy, left ventricular ejection fraction (LVEF) decreased to \<50%, symptomatic congestive heart failure occurred, or toxicity leading to permanent treatment discontinuation was experienced.
• Known hypersensitivity and/or contraindications to corticosteroids (including but not limited to active peptic ulcer disease, severe hypertension, severe hypokalemia, glaucoma, etc.).
• Use of strong CYP3A4 inhibitors within 14 days prior to randomization.
• History of hypersensitivity to any component of the investigational drug(s) or any known excipient.
• Spinal cord compression or clinically active central nervous system (CNS) metastases, defined as untreated or symptomatic, or requiring corticosteroids or anticonvulsants to manage related symptoms. Participants are eligible if they have been clinically stable for \>4 weeks after treatment for brain metastases without requiring corticosteroids or anticonvulsants and have recovered from acute toxicities of radiotherapy. Whole-brain radiotherapy or stereotactic radiosurgery must have been completed at least 2 weeks prior to study enrollment.
• Active malignancy within 3 years prior to randomization, except for the breast cancer under investigation in this trial and any locally curable tumors that have undergone definitive treatment (e.g., resected basal cell or squamous cell skin cancer, superficial bladder cancer, carcinoma in situ of the cervix or breast, early-stage thyroid cancer, etc.).
• Uncontrolled or significant cardiovascular or cerebrovascular diseases, including but not limited to:
• New York Heart Association (NYHA) Class II or higher congestive heart failure, unstable angina, myocardial infarction, or arrhythmia causing hemodynamic instability within 6 months prior to randomization;
• Primary cardiomyopathy (e.g., dilated cardiomyopathy, hypertrophic cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy, restrictive cardiomyopathy, unclassified cardiomyopathy);
• History of clinically significant QT interval prolongation, or QTcF (calculated using Fridericia's formula) \>480 ms during screening;
• Arterial/venous thrombotic events within 6 months prior to randomization, such as cerebrovascular accident (including transient ischemic attack, cerebral hemorrhage, cerebral infarction), deep vein thrombosis, and pulmonary embolism;
• Uncontrolled hypertension (systolic blood pressure \>160 mmHg and/or diastolic blood pressure \>100 mmHg).

Sponsors & Collaborators

• Shanghai JMT-Bio Inc.: lead

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Trastuzumab; pertuzumab; Docetaxel

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This study is a randomized, controlled, open-label, multicenter, phase II superiority clinical trial.

Study Record Dates

• First Submitted: April 15, 2026
• First Posted: April 22, 2026
• Study Start (Estimated): May 30, 2026
• Primary Completion (Estimated): May 29, 2027
• Study Completion (Estimated): May 30, 2027
• Last Updated: April 22, 2026

Record last verified: 2026-04