Comparing disitamab vedotin and pyrotinib to standard treatment for HER2-positive advanced breast cancer

Disitamab Vedotin in Combination With Pyrotinib Versus THP in the First-line Treatment for HER2-positive Advanced Breast Cancer, a Multicentre, Randomized, Double-blind Controlled, Phase III Trial

This study is testing a new combination of disitamab vedotin and pyrotinib to see if it works better than the standard treatment for people with newly diagnosed HER2-positive advanced breast cancer.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 312 (estimated)
• Ages: 18 Years to 75 Years
• Sex: Female
• Sponsor: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University (Academic / other)
• Drugs / interventions: chemotherapy, disitamab, trastuzumab, pertuzumab, pyrotinib
• Locations: 1 site (Guangzhou, Guangdong)
• Trial ID: NCT06278870 on ClinicalTrials.gov

What this trial studies

This phase III clinical trial aims to evaluate the efficacy and safety of disitamab vedotin combined with pyrotinib compared to the standard first-line treatment of paclitaxel with trastuzumab and pertuzumab (THP) in patients with newly diagnosed HER2-positive metastatic breast cancer. Participants will receive the experimental treatment for 6-8 cycles, followed by maintenance therapy with trastuzumab. The study also seeks to explore how biomarkers may influence the clinical outcomes of the treatments. It is a multicenter, randomized, double-blind controlled trial designed to provide robust data on treatment effectiveness.

Who should consider this trial

Good fit: Ideal candidates are adult female patients aged 18-75 with pathologically confirmed HER2-positive metastatic breast cancer who have not received prior chemotherapy for this condition.

Not a fit: Patients with previous chemotherapy for metastatic breast cancer or those with a performance status score greater than 2 may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could offer a more effective first-line option for patients with HER2-positive advanced breast cancer.

How similar studies have performed: Other studies have shown promising results with similar targeted therapies in HER2-positive breast cancer, indicating potential for success in this approach.

Eligibility criteria

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).

Where this trial is running

Guangzhou, Guangdong

• Sun Yat-sen Memorial Hospital,Sun Yat-sen University — Guangzhou, Guangdong, China (Recruiting)

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