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

A Randomized, Controlled, Open-Label, Multicenter, Phase 3 Study to Compare the Efficacy and Safety of JSKN003 Versus Trastuzumab Emtansine (T-DM1) for HER2-Positive, Advanced Breast Cancer Subjects

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.

Study Overview

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

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 Type: Interventional
• Enrollment (Estimated): 228
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Clinical Trials Information Group officer; Phone Number: 86-0311-69085587; Email: ctr-contact@cspc.cn
• Study Contact Backup: Name: Zhimin Shao, M.D.; Phone Number: +86 18017312288; Email: :szm@163.com

Study Locations

• China
  • Shanghai, China
    • Recruiting
    • Fudan University Shanghai Cancer Center
    • Contact: Zhimin Shao, M.D.; Phone Number: +86 18017312288; Email: szm@163.com

Participation Criteria

Eligibility Criteria

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

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: JSKN003; Received JSKN003 as a sterile intravenous (IV) solution at a dose of 6.3 mg/kg every 3 weeks (Q3W).	Drug: JSKN003; Administered intravenously according to protocol.
Active Comparator: T-DM1; Received T-DM1 in accordance with the approved label.	Drug: Trastuzumab emtansine (T-DM1); Administered intravenously according to the approved label.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Progression-Free Survival (PFS) by BIRC	Up to approximately 4 years

Secondary Outcome Measures

Outcome Measure	Time Frame
Overall Survival (OS)	Up to approximately 4 years
Disease Control Rate (DCR)	Up to approximately 4 years
Progression-free survival (PFS) by investigator	Up to approximately 4 years
Objective Response Rate (ORR)	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.

Collaborators and Investigators

• Sponsor: Shanghai JMT-Bio Inc.
• Investigators: Principal Investigator: Zhimin Shao, M.D. Organizational Affiliatio, Fudan University

Study record dates

Study Major Dates

• Study Start (Actual): February 18, 2025
• Primary Completion (Estimated): October 13, 2026
• Study Completion (Estimated): December 31, 2028

Study Registration Dates

• First Submitted: January 6, 2025
• First Submitted That Met QC Criteria: February 20, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 19, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Breast Neoplasms; Antineoplastic Agents, Immunological; Antineoplastic Agents; Immunologic Factors; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Immunoconjugates; Immunotoxins; Trastuzumab; Ado-Trastuzumab Emtansine; Maytansine
• Other Study ID Numbers: JSKN003-301

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No