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

Sun Yat-sen University

Status and phase: Enrolling; Phase 3

Conditions: HER2-positive Metastatic Breast Cancer; First-line Treatment

Treatments: Drug: trastuzumab; Drug: taxane drug; Drug: Pyrotinib; Drug: disitamab vedotin; Drug: Pertuzumab

Study type: Interventional

Funder types: Other

Identifiers

NCT06278870

SYSKY-2023-431-02

Details and patient eligibility

About

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 receptor 2 (HER2) positive advanced breast cancer, and to explore the impact of biomarkers on clinical efficacy and safety. The main questions it aims to answer are:

• Analyse the efficacy and safety of disitamab vedotin in combination with pyrotinib versus the standard first-line treatment of THP.
• Explore the impact of biomarkers on clinical efficacy and safety of the combination of disitamab vedotin in combination with pyrotinib treatment.

Participants in the experimental group will receive disitamab vedotin in combination with pyrotinib for 6-8 cycles (each cycle lasting 28 days), followed by maintenance treatment with trastuzumab in combination with pyrotinib. Participants in the control group will receive paclitaxel in combination with trastuzumab and pertuzumab for 6-8 cycles (each cycle lasting 21 days), followed by maintenance treatment with trastuzumab and pertuzumab.

Researchers will compare disitamab vedotin in combination with pyrotinib versus the standard first-line treatment of paclitaxel in combination with trastuzumab and pertuzumab to see if disitamab vedotin in combination with pyrotinib could be a new option for first-line treatment of HER2-positive metastatic breast cancer.

Enrollment: 312 estimated patients

Sex: Female

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

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.

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).

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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312 participants in 2 patient groups

disitamab vedotin in combination with pyrotinib

Experimental group

Description:

disitamab 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.

Treatment:

Drug: disitamab vedotin

Drug: trastuzumab

Drug: Pyrotinib

taxane drug in combination with trastuzumab and pertuzumab

Active Comparator group

Description:

taxane 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.

Treatment:

Drug: Pertuzumab

Drug: taxane drug

Drug: trastuzumab