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

NCT06278870 | Recruiting Phase 3 FDA Drug

• 1 other identifier: SYSKY-2023-431-02
• Study Type: interventional
• Target: 312
• Locations: 1 country
• Sites: 1

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 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.

Conditions

HER2-positive Metastatic Breast Cancer; First-line Treatment

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival (PFS)

  From enrollment to progression or death (for any reason)

  Estimated 30 months

Secondary Outcomes (7)

• Overall Survival (OS)

  Estimated 8 years

• Disease control rate (DCR)

  Estimated 30 months

• Objective Response Rate (ORR)

  Estimated 30 months

• Clinical Benefit rate (CBR)

  Estimated 30 months

• Adverse Events (Based on CTCAE 5.0 standards)

  From informed consent through 28 days following treatment completion

Study Arms (2)

disitamab vedotin in combination with pyrotinib

EXPERIMENTAL

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.

Drug: disitamab vedotin; Drug: Pyrotinib; Drug: trastuzumab

taxane drug in combination with trastuzumab and pertuzumab

ACTIVE COMPARATOR

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.

Drug: trastuzumab; Drug: Pertuzumab; Drug: taxane drug

Interventions

disitamab vedotin DRUG

disitamab vedotin 2mg/kg iv q2w

Also known as: RC-48

disitamab vedotin in combination with pyrotinib

Pyrotinib DRUG

pyrotinib 400mg po q28d

disitamab vedotin in combination with pyrotinib

trastuzumab DRUG

trastuzumab 8mg/kg for the first cycle, 6mg/kg for subsequent treatments iv q21d

disitamab vedotin in combination with pyrotinib; taxane drug in combination with trastuzumab and pertuzumab

Pertuzumab DRUG

pertuzumab 840mg for the first cycle, 420mg for subsequent treatments iv q21d

taxane drug in combination with trastuzumab and pertuzumab

taxane drug DRUG

Docetaxel/paclitaxel/albumin paclitaxel/liposomal paclitaxel, dosage and administration are determined according to the latest version of the NCCN and CSCO breast cancer guideline recommendations

taxane drug in combination with trastuzumab and pertuzumab

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult female patients (age 18-75 years) with metastatic breast cancer confirmed by pathology or imaging;
• Pathologically confirmed HER2 positive (definition: Immunohistochemistry(IHC) 3+, or IHC 2+ and Fluorescent In Situ Hybridization(FISH) amplification);
• No previous chemotherapy regimen for metastatic breast cancer;
• At least one measurable lesion exists (Response Evaluation Criteria in Solid Tumors(RECIST) 1.1);
• Eastern Cooperative Oncology Group(ECOG) performance status score ≤ 2 and expected survival of not less than 3 months;
• 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);
• Patients with adequate organ function before enrollment:
• White Blood Cell (WBC) ≥ 3.0 x 10\^9/L;
• Neutrophil granulocyte (ANC) ≥1.5 x 10\^9/L;
• Platelet (PLT) ≥70×10\^9/L;
• Liver, kidney, and cardiac function tests are essentially normal (based on the normal values in the laboratory of each study center):
• Total bilirubin (TBIL) ≤ 3 x Upper Limit of Normal (ULN);
• Alanine aminotransferase (ALT/AST) ≤ 2.5 x ULN (≤ 5 x ULN in patients with liver metastases);
• serum creatinine ≤ 1.5 x ULN or creatinine clearance (Ccr) ≥ 60 ml/min;
• Normal cardiac function;

You may not qualify if:

• Pathology suggestive of HER2 negativity (IHC 2+ and FISH-, or IHC 1+);
• Patients with known hypersensitivity to the active ingredient or other components of the study drug;
• 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;
• 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).

Sponsors & Collaborators

• Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University: lead

Study Sites (1)

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

Guangzhou, Guangdong, 510000, China

RECRUITING

Related Publications (13)

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MeSH Terms

Interventions

disitamab vedotin; RC48 antibody; pyrotinib; Trastuzumab; pertuzumab

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 7, 2023
• First Posted: February 26, 2024
• Study Start: September 6, 2023
• Primary Completion (Estimated): June 30, 2031
• Study Completion (Estimated): June 30, 2031
• Last Updated: February 26, 2024

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)