Pyrotinib and Trastuzumab Combined With Dalpiciclib Versus Combined With Docetaxel in Advanced HER2-Positive Breast Cancer

Summary

The DIAMOND study (DIAMOND-01) is a multicenter, randomized, open-label, non-inferiority Phase III clinical trial conducted by Fudan University Shanghai Cancer Center. The study aims to evaluate the efficacy and safety of an oral, "non-intravenous" regimen (pyrotinib + trastuzumab \[subcutaneous\] + dalpiciclib) compared to a standard intravenous chemotherapy-containing regimen (pyrotinib + trastuzumab \[subcutaneous\] + docetaxel) in patients with advanced HER2-positive breast cancer.

Approximately 502 patients with histologically confirmed advanced HER2-positive breast cancer who have received at most one prior line of systemic therapy (including anti-HER2 treatment) in the advanced setting will be randomized 1:1 to either the experimental or control arm. Stratification factors include ER status and presence of visceral metastases. The primary endpoint is Progression-Free Survival (PFS). Key secondary endpoints include Overall Survival (OS), Objective Response Rate (ORR), Disease Control Rate (DCR), Clinical Benefit Rate (CBR), safety, and patient-reported quality of life. Exploratory endpoints involve correlating circulating tumor cells (CTCs) and PAM50 molecular subtyping with survival outcomes.

This study seeks to determine if the all-oral, chemotherapy-free combination is non-inferior to the standard chemo-containing regimen, potentially offering a less toxic and more convenient treatment option for patients with advanced HER2-positive breast cancer.

Conditions

• Breast Cancer

Interventions

DRUG

Pyrotinib 320mg po qd d1-d21 q3w and Trastuzumab 600mg IH d1 q3w Combined with Dalpicicli 125mg po gd d1-d21 q4w

Pyrotinib: 320 mg, administered orally once daily. It should be taken within 30 minutes after breakfast. Dosing continues until disease progression or unacceptable toxicity occurs as defined by the protocol. If a dose is missed, underdosed, or vomiting occurs after ingestion, the missed dose should not be made up. The event should be recorded, and the next dose should be taken as scheduled. Dalpiciclib: 125 mg, administered orally once daily at approximately the same time each day. Patients must fast for at least 1 hour before and after administration. It is taken continuously for 21 days, followed by a 7-day break, comprising one 28-day treatment cycle. Trastuzumab: A fixed dose of 600 mg (not weight-based) administered subcutaneously every three weeks. Each injection should be completed over 2-5 minutes. Endocrine Therapy: For HR-positive patients, the decision to administer endocrine therapy in the experimental group will be at the investigator's discretion after 6 cycles

DRUG

Pyrotinib 320mg po qd d1-d21 q3w and Trastuzumab 600mg IH d1 q3w Combined with Docetaxel 75mg/m² ivgtt d1 q3w,

Pyrotinib: 400 mg, administered orally once daily. It should be taken within 30 minutes after breakfast. Dosing continues until disease progression or unacceptable toxicity occurs as defined by the protocol. If a dose is missed, underdosed, or vomiting occurs after ingestion, the missed dose should not be made up. The event should be recorded, and the next dose should be taken as scheduled. Trastuzumab: A fixed dose of 600 mg (not weight-based) administered subcutaneously every three weeks. Each injection should be completed over 2-5 minutes. Docetaxel: 75 mg/m², administered by intravenous infusion every 21 days as one cycle, for a total of 6 cycles.For HR-positive patients, whether to administer endocrine therapy in the experimental group after 6 cycles of docetaxel may be determined at the investigator's discretion. However, the use of CDK4/6 inhibitors is prohibited.

Sponsors & Collaborators

• Fudan University

  lead OTHER

Principal Investigators

• Hongxia Wang, Chief physician · Fudan University Principal Investigator Biyun Wang , Chief physician Fudan University

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

FEMALE

Healthy Volunteers

No

Timeline & Regulatory

Start

2025-02-12

Primary Completion

2028-12-30

Completion

2029-12-30

Countries

• China

Study Locations