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

Official title

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

Overview

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.

Interventions

• Drug JSKN003
  Administered intravenously according to protocol.
• Drug Trastuzumab emtansine (T-DM1)
  Administered intravenously according to the approved label.

Primary outcome measures

• Progression-Free Survival (PFS) by BIRC [Time frame: Up to approximately 4 years]

Secondary outcome measures (9)

• Progression-free survival (PFS) by investigator [Time frame: Up to approximately 4 years]
• Overall Survival (OS) [Time frame: Up to approximately 4 years]
• Objective Response Rate (ORR) [Time frame: Up to approximately 4 years]
• Disease Control Rate (DCR) [Time frame: Up to approximately 4 years]
• Duration of Response (DoR) [Time frame: Up to approximately 4 years]
• Incidence and severity of TEAE and SAE [Time frame: 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 [Time frame: 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 [Time frame: 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 [Time frame: 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.]

Eligibility criteria

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Fudan University Shanghai Cancer Center — Shanghai

Identifiers

NCT: NCT06846437 · JSKN003-301

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗