Disitamab Vedotin + Pyrotinib Versus THP in the First-line Treatment for HER2+ Advanced Breast Cancer Clinical Trial

Registration Number
NCT06278870
Lead Sponsor
Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
Brief Summary

The goal of this multicentre, randomized, double-blind controlled, phase III clinical trial is to compare the efficacy and safety of disitamab vedotin in combination with pyrotinib versus the standard first-line treatment of paclitaxel in combination with trastuzumab and pertuzumab (THP) for newly diagnosed recurrent/metastatic Human epidermal growth factor ...

Detailed Description

Not available

Recruitment & Eligibility

Status
RECRUITING
Sex
Female
Target Recruitment
312
Inclusion Criteria

  1. Adult female patients (age 18-75 years) with metastatic breast cancer confirmed by pathology or imaging;

  2. Pathologically confirmed HER2 positive (definition: Immunohistochemistry(IHC) 3+, or IHC 2+ and Fluorescent In Situ Hybridization(FISH) amplification);

  3. No previous chemotherapy regimen for metastatic breast cancer;

  4. At least one measurable lesion exists (Response Evaluation Criteria in Solid Tumors(RECIST) 1.1);

  5. Eastern Cooperative Oncology Group(ECOG) performance status score ≤ 2 and expected survival of not less than 3 months;

  6. Prior treatment-related toxicity at enrollment must have resolved to National Cancer Institute(NCI) Common Terminology Criteria for Adverse Events(CTCAE) (version 5.0) ≤ 1 degree (except for alopecia or other toxicity that, in the judgment of the investigator, is not considered a risk to the safety of the patient);

  7. Patients with adequate organ function before enrollment:

    1. White Blood Cell (WBC) ≥ 3.0 x 10^9/L;
    2. Neutrophil granulocyte (ANC) ≥1.5 x 10^9/L;
    3. Platelet (PLT) ≥70×10^9/L;

  8. Liver, kidney, and cardiac function tests are essentially normal (based on the normal values in the laboratory of each study center):

    1. Total bilirubin (TBIL) ≤ 3 x Upper Limit of Normal (ULN);
    2. Alanine aminotransferase (ALT/AST) ≤ 2.5 x ULN (≤ 5 x ULN in patients with liver metastases);
    3. serum creatinine ≤ 1.5 x ULN or creatinine clearance (Ccr) ≥ 60 ml/min;

  9. . Normal cardiac function;

    1. Left ventricular ejection fraction (LVEF) ≥ 55%;
    2. QT-interval corrected with Fridericia (QTcF) ≤ 470ms;

  10. Hormone receptor status is clear;

  11. Female patients of childbearing potential who have a negative pregnancy test and agree to use an effective non-hormonal method of contraception during treatment and for at least 6 months after the last dose of the test drug;

  12. Able to understand the study process, voluntarily participate in this study, and sign an informed consent form.

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Exclusion Criteria
  1. Pathology suggestive of HER2 negativity (IHC 2+ and FISH-, or IHC 1+);
  2. Patients with known hypersensitivity to the active ingredient or other components of the study drug;
  3. Patients during pregnancy or lactation, patients with childbearing potential tested positive in a baseline pregnancy test, or patients unwilling to take effective contraceptive measures throughout the trial;
  4. Patients not eligible for this study judged by the investigator, a pre-existing disease or condition that may interfere with participation in the study or any serious medical disorder that may interfere with the safety of the subject (e.g., uncontrolled heart disease, high blood pressure, active or uncontrolled infections, active hepatitis B virus infection).
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Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
taxane drug in combination with trastuzumab and pertuzumabtaxane drugtaxane drug (Docetaxel/Paclitaxel/Albumin Paclitaxel/Liposomal Paclitaxel, dosing and administration per latest National Comprehensive Cancer Network(NCCN) and Chinese Society of Clinical Oncology(CSCO) breast cancer guidelines) + Trastuzumab initially at 8mg/kg IV followed by 6mg/kg IV every 21 days + Pertuzumab initially at 840mg IV followed by 420mg IV every 21 days, with each 21-day cycle. After 6-8 cycles, continuing with Trastuzumab at 6mg/kg IV every 21 days + Pertuzumab at 420mg IV every 21 days for maintenance.
disitamab vedotin in combination with pyrotinibPyrotinibdisitamab vedotin 2mg/kg IV every 14 days + Pyrotinib 400mg PO daily, with each 28-day cycle. After 6-8 cycles, adding Trastuzumab initially at 8mg/kg IV followed by 6mg/kg IV every 21 days + Pyrotinib 400mg PO daily for maintenance.
disitamab vedotin in combination with pyrotinibdisitamab vedotindisitamab vedotin 2mg/kg IV every 14 days + Pyrotinib 400mg PO daily, with each 28-day cycle. After 6-8 cycles, adding Trastuzumab initially at 8mg/kg IV followed by 6mg/kg IV every 21 days + Pyrotinib 400mg PO daily for maintenance.
taxane drug in combination with trastuzumab and pertuzumabtrastuzumabtaxane drug (Docetaxel/Paclitaxel/Albumin Paclitaxel/Liposomal Paclitaxel, dosing and administration per latest National Comprehensive Cancer Network(NCCN) and Chinese Society of Clinical Oncology(CSCO) breast cancer guidelines) + Trastuzumab initially at 8mg/kg IV followed by 6mg/kg IV every 21 days + Pertuzumab initially at 840mg IV followed by 420mg IV every 21 days, with each 21-day cycle. After 6-8 cycles, continuing with Trastuzumab at 6mg/kg IV every 21 days + Pertuzumab at 420mg IV every 21 days for maintenance.
disitamab vedotin in combination with pyrotinibtrastuzumabdisitamab vedotin 2mg/kg IV every 14 days + Pyrotinib 400mg PO daily, with each 28-day cycle. After 6-8 cycles, adding Trastuzumab initially at 8mg/kg IV followed by 6mg/kg IV every 21 days + Pyrotinib 400mg PO daily for maintenance.
taxane drug in combination with trastuzumab and pertuzumabPertuzumabtaxane drug (Docetaxel/Paclitaxel/Albumin Paclitaxel/Liposomal Paclitaxel, dosing and administration per latest National Comprehensive Cancer Network(NCCN) and Chinese Society of Clinical Oncology(CSCO) breast cancer guidelines) + Trastuzumab initially at 8mg/kg IV followed by 6mg/kg IV every 21 days + Pertuzumab initially at 840mg IV followed by 420mg IV every 21 days, with each 21-day cycle. After 6-8 cycles, continuing with Trastuzumab at 6mg/kg IV every 21 days + Pertuzumab at 420mg IV every 21 days for maintenance.
Primary Outcome Measures
NameTimeMethod
Progression Free Survival (PFS)Estimated 30 months

From enrollment to progression or death (for any reason)

Secondary Outcome Measures
NameTimeMethod
Disease control rate (DCR)Estimated 30 months

Ratio of complete response (CR) , partial response (PR) and stable disease (SD) in all subjects

Adverse Events (Based on CTCAE 5.0 standards)From informed consent through 28 days following treatment completion

Safety

Quality of Life (QoL) by Functional Assessment of Cancer Therapy for Breast Cancer (FACT-B)Estimated 30 months

QoL was assessed using FACT-B. FACT-B is a 37-item questionnaire with 5 subscales assessing physical, social, emotional, and functional well-being, with scores ranging from 0 to 4 for each question. Higher scores generally indicating a better quality of life.

Overall Survival (OS)Estimated 8 years

From enrollment to death (for any reason)

Clinical Benefit rate (CBR)Estimated 30 months

Ratio of CR,PR and SD greater than or equal to 24 weeks in all subjects

Objective Response Rate (ORR)Estimated 30 months

Ratio of CR and PR in all subjects

Exploration of biomarkersEstimated 30 months

Next Generation Gene Sequencing (NGS) detection of tissue and blood specimens, including ERBB1/ERBB2/ERBB3/ERBB4/AKT/TP53/PIK3CA and so on. Objective to explore the correlation between biomarkers and the objective response rate (ORR), as well as progression-free survival (PFS).

Trial Locations

Locations (1)

Sun Yat-sen Memorial Hospital,Sun Yat-sen University

🇨🇳

Guangzhou, Guangdong, China

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