JSKN003 Versus Trastuzumab Emtansine (T-DM1) for HER2-Positive, Advanced Breast Cancer

Phase 3

Recruiting

• Conditions: Unrespectable Locally Advanced and or Metastatic HER2 Positive Breast Cancer Participants
• Interventions: Drug: JSKN003; Drug: Trastuzumab emtansine (T-DM1)

• Registration Number: NCT06846437
• Lead Sponsor: Shanghai JMT-Bio Inc.

Brief Summary

This study is designed to compare the safety and efficacy of JSKN003 versus T-DM1 in unrespectable locally advanced and/or metastatic HER2-positive breast cancer participants previously treated with trastuzumab and taxane.

Detailed Description

This is a randomized, controlled, open-label, multicenter, phase 3 clinical study to compare the efficacy and safety of JSKN003 versus T-DM1 in unresectable locally advanced and/or metastatic HER2-positive breast cancer participants previously treated with trastuzumab and taxane. Participants will be treated with JSKN003 at 6.3 mg/kg or trastuzumab emtansine at 3.6 mg/kg every 3 weeks (Q3W). Participants will continue to receive treatment until disease progression, intolerable toxicity, withdrawal of informed consent, death, or any other reasons for treatment discontinuation, whichever occurs first.

Study Timeline

• Study First Submitted: 2025-01-06
• Status Verified: 2025-02
• Study Start: 2025-02-18
• Study First Submitted QC: 2025-02-20
• Study First Posted: 2025-02-26
• Last Update Submitted: 2025-03-19
• Last Update Posted: 2025-03-24
• Primary Completion: 2026-10-13
• Study Completion: 2028-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 228

Inclusion Criteria

• 1. Voluntarily agree to participate in the study and sign the informed consent.
• 2.Age≥18 years old.
• 3.Patients with unresectable locally advanced or metastatic breast cancer confirmed by histology or cytology.
• 4.Confirmed to be HER2 positive (HER2-positive is defined as IHC 3+ or IHC 2+ with ISH positive) by the pathology department of participating study center.
• 5.Have received treatment regimen including trastuzumab (allowed marketed trastuzumab biosimilars) or inetetamab with radiologic or pathologic progression/ relapse during the advanced stage, during neoadjuvant or adjuvant therapy, or within 12 months after treatment.
• 6.Previously treated with taxanes.
• 7.Had radiologic and/or pathologic progression or intolerance of the latest systemic anti-tumor therapy.
• 8.At least one extracranial measurable lesion at baseline according to RECIST 1.1 criteria.
• 9.ECOG PS of 0 - 1.
• 10.Patients with adequate organ and bone marrow functions.
• 11.Expected survival ≥ 3 months.
• 12.Female and male patients of childbearing age agree to take adequate contraceptive measures during and upon completion of the study for 7 months after the last dose of JSKN003 or T-DM1.

Exclusion Criteria

• 1. Have previously been treated with an anti-HER2 ADC loaded with topoisomerase I inhibitors or medenosin derivative 1 (DM1) or have relapsed after receiving such therapy during or within 12 months after the adjuvant/neo-adjuvant setting or in the advanced stage.
• 2.History of any other malignant tumors within three years before randomization.
• 3.With uncontrollable serous effusion within 14 days before randomization, which requires frequent drainage or medical intervention.
• 4.Known contraindication to T-DM1or not suitable to receive JSKN003 or T-DM1 by investigator.
• 5.Has not recovered from adverse reactions caused by previous anti-tumor treatments to ≤ Grade 1 (refer to NCI CTCAE 5.0) or baseline (excluding grade 2 alopecia, hyperpigmentation, simple laboratory test abnormalities, and other toxicity for a non-safety risk by investigators).
• 6.Received immunotherapy, macromolecular targeted therapy or other anti-tumor biological therapy within 4 weeks before randomization, or received palliative radiotherapy, endocrine therapy, cytotoxic drug chemotherapy and small molecular targeted drug therapy within 2 weeks before randomization, or received traditional Chinese medicine preparations with anti-tumor indications within 2 weeks before randomization.
• 7.Major organ surgery within 28 days before randomization.
• 8.Untreated (including baseline findings) or unstable cerebral parenchymal metastasis, spinal cord metastasis or compression, and cancerous meningitis.
• 9.The cumulative amount of previous exposure to anthracyclines has reached the pre-specified dosage.
• 10.History of LVEF < 40% during prior anti-HER2 drug therapy or symptomatic congestive heart failure (CHF).
• 11.Serious or uncontrolled cardiovascular disease.
• 12.History of (non-infectious) interstitial lung disease/pneumonitis requiring therapy or grade ≥3 interstitial lung disease/ pneumonitis during previous anti-tumor treatments.
• 13.Active infections requiring intravenous antibiotics, antivirals, or antifungals within 14 days before randomization.
• 14. Active hepatitis B or hepatitis C.
• 15.History of immunodeficiency or HIV antibody test positive at screening.
• 16.Received a potent inhibitor of CYP3A4 within 14 days prior to randomization or during study treatment.
• 17.Pregnant or nursing females;
• 18.Other reasons enrolled in this clinical trial as considered unsuitable by the investigator.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
JSKN003	JSKN003	Received JSKN003 as a sterile intravenous (IV) solution at a dose of 6.3 mg/kg every 3 weeks (Q3W).
T-DM1	Trastuzumab emtansine (T-DM1)	Received T-DM1 in accordance with the approved label.

Primary Outcome Measures

Name	Time	Method
Progression-Free Survival (PFS) by BIRC	Up to approximately 4 years

Secondary Outcome Measures

Name	Time	Method
Progression-free survival (PFS) by investigator	Up to approximately 4 years
Overall Survival (OS)	Up to approximately 4 years
Objective Response Rate (ORR)	Up to approximately 4 years
Disease Control Rate (DCR)	Up to approximately 4 years
Duration of Response (DoR)	Up to approximately 4 years
Incidence and severity of TEAE and SAE	From the signing of informed consent to the safety follow-up period or before starting a new anti-tumor therapy, whichever occurs first, assessed up to approximately 4 years.
Cmax of JSKN003	Cycles 1, 2, 3, 4 (each cycle is 3 weeks), and every 4 cycles starting from Cycle 4; End of treatment and safety follow-up visit, for approximately 4 years
AUC of JSKN003	Cycles 1, 2, 3, 4 (each cycle is 3 weeks), and every 4 cycles starting from Cycle 4; End of treatment and safety follow-up visit, for approximately 4 years
Incidence of anti-drug antibodies (ADA) to JSKN003	Pre-dose for Cycles 1, 2, 3, 4 (each cycle is 3 weeks), and every 4 cycles starting from Cycle 4; End of treatment and safety follow-up visit, for approximately 4 years.

Trial Locations

Locations (1)

Fudan University Shanghai Cancer Center; 🇨🇳 Shanghai, China