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

May 28, 2026 updated by: Hongxia Wang, Fudan University

A Multicenter, Non-Inferiority, Randomized Phase III Clinical Study Comparing Pyrotinib and Trastuzumab Combined With Dalpiciclib Versus Combined With Docetaxel in the Treatment of Advanced HER2-Positive Breast Cancer

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
502

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.
  • Name: Hongxia Wang Chief physician
  • Phone Number: 86-138196379
  • Email: whx365@126.com

Study Contact Backup

Study Locations

  • China
    • Shanghai Municipality
      • Shanghai, Shanghai Municipality, China, 200230
        • Recruiting
        • Fudan Cancer Hospital
        • Contact:
        • Principal Investigator:
          • Hongxia Wang, Chief physician
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Age ≥ 18 years.
  2. Patients with histopathologically confirmed recurrent/metastatic breast cancer that is HER2-positive (HER2 positivity is defined as IHC 3+, or IHC 2+/FISH amplified), based on the most recent pathological report.
  3. Hormone receptor status is known, based on the most recent pathological report.
  4. At least one measurable lesion meeting RECIST 1.1 criteria.
  5. Have received no more than one prior line of systemic anti-tumor therapy for the advanced stage, which may include anti-HER2 therapy, chemotherapy, targeted therapy, immunotherapy, etc.
  6. ECOG performance status of 0 to 1.

  7. Adequate organ function meeting the following requirements:

    • Blood Routine: ANC ≥ 1.5 × 10⁹/L; PLT ≥ 75 × 10⁹/L; Hb ≥ 90 g/L (transfusion or medication to maintain hemoglobin level is permitted).
    • Blood Biochemistry: TBIL ≤ 1.5 × ULN; ALT and AST ≤ 3 × ULN (≤ 5.0 × ULN in patients with liver metastases); BUN or Cr ≤ 1.5 × ULN OR Creatinine Clearance ≥ 50 mL/min (calculated by Cockcroft-Gault formula).
    • 12-Lead ECG: QTcF < 470 ms for females, < 450 ms for males.
    • Cardiac Ultrasound: LVEF ≥ 50%.

  8. Prior use of TKI drugs (including but not limited to pyrotinib or neratinib) in the neoadjuvant/adjuvant setting is permitted, provided the following conditions are both met:

    • The patient did not experience disease progression or recurrence/metastasis during the prior TKI therapy.
    • There was a period of ≥ 6 months between the discontinuation of the prior TKI and the occurrence of disease progression or recurrence/metastasis.
  9. Recovery from any adverse events related to prior anti-tumor therapies to Grade ≤1 (according to NCI-CTCAE v5.0) before the first dose of study drug, with the exception of: a. Alopecia; b. Pigmentation.
  10. The subject voluntarily participates in the study, has signed the Informed Consent Form (ICF), demonstrates good compliance, and is willing to cooperate with follow-up

Exclusion Criteria:

  1. Presence of symptomatic brain metastases or leptomeningeal metastases.
  2. Active brain metastases, except for asymptomatic brain metastases or those that have been stable for at least 4 weeks after local treatment.
  3. Inability to swallow, presence of intestinal obstruction, or other factors affecting drug administration and absorption.
  4. Presence of uncontrolled third-space fluid accumulation (e.g., massive pleural effusion or ascites) that cannot be managed by drainage or other methods.
  5. Received radiotherapy, chemotherapy, or targeted therapy within 4 weeks prior to enrollment, or endocrine therapy within 2 weeks prior to enrollment. (Bisphosphonates used for treating bone metastases or preventing osteoporosis are excluded from this restriction). Or, current participation in any interventional drug clinical trial.
  6. Pregnant or lactating female subjects, or subjects of childbearing potential with a positive baseline pregnancy test, or unwilling to use effective contraception.
  7. History of other active malignancies within the past 5 years (excluding cured basal cell carcinoma of the skin, carcinoma in situ of the cervix, and cutaneous squamous cell carcinoma).
  8. Major surgical procedure or significant trauma within 4 weeks prior to randomization, or anticipation of the need for major surgery during the study.
  9. Known history of allergy to any component of the study drug regimen.
  10. Subjects with cardiac insufficiency, including but not limited to: congestive heart failure, transmural myocardial infarction, angina pectoris requiring medication, clinically significant valvular heart disease, and high-risk arrhythmias.
  11. Active hepatitis (For hepatitis B: HBsAg positive AND HBV DNA ≥ 1000 IU/mL; For hepatitis C: HCV antibody positive AND HCV RNA above the upper limit of normal).
  12. Uncontrolled hypertension (resting blood pressure: systolic > 160 mmHg or diastolic > 100 mmHg).
  13. History of definite neurological or psychiatric disorders, including epilepsy or dementia.
  14. Any other condition that, in the investigator's judgment, renders the patient unsuitable for participation in this study. This includes any concomitant illness or condition that could interfere with study participation, or any serious medical disorder that might affect subject safety (e.g., active or uncontrolled infection, severe diabetes, immunodeficiency disease, etc.).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Arm1
Pyrotinib 320mg po qd d1-d21 q3w and Trastuzumab 600mg IH d1 q3w Combined with Dalpicicli 125mg po gd d1-d21 q4w
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
Active Comparator: Arm2
Pyrotinib 320mg po qd d1-d21 q3w and Trastuzumab 600mg IH d1 q3w Combined with Docetaxel 75mg/m² ivgtt d1 q3w, Docetaxel was discontinued after 6 cycles, while Pyrotinib and trastuzumab were continued as maintenance therapy.
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.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
PFS
Time Frame: from initial treatment until disease progression, death, loss to follow-up, or study completion，up to 3 years
PFS is the time from the date of first dose until the date of objective radiographic disease progression or death (by any cause in the absence of progression).
from initial treatment until disease progression, death, loss to follow-up, or study completion，up to 3 years

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
OS
Time Frame: from initial treatment until death, up to 5 years
OS is the time from the date of frst dose until the date of death by any cause.
from initial treatment until death, up to 5 years
ORR
Time Frame: from initial treatment until disease progression or study completion , up to 36 months
ORR is the percentage of evaluable patients with a confirmed investigator-assessed response of CR (complete response) or PR (partial response) per RECIST v1.1 and will be evaluated at baseline, at the time point of every 6 weeks.
from initial treatment until disease progression or study completion , up to 36 months
DCR
Time Frame: From initial treatment until disease progression or study completion ，up to 36 months
DCR is the percentage of evaluable patients with a confirmed investigator-assessed response of CR (complete response), PR (partial response) or SD (stable disease) per RECIST v1.1 and will be evaluated at baseline, at the time point of every 6 weeks.
From initial treatment until disease progression or study completion ，up to 36 months
Clinical Benefit Rate (CBR)
Time Frame: From initial treatment until disease progression or study completion ，up to 36 months.
Proportion of patients achieving complete response (CR), partial response (PR), or stable disease (SD) lasting for at least 24 weeks per RECIST 1.1 criteria.
From initial treatment until disease progression or study completion ，up to 36 months.
safety assessment
Time Frame: from initial treatment until disease progression, death, loss to follow-up, or study completion，up to 3 years
Number and percentage of patients experiencing adverse events (AEs) and serious adverse events (SAEs). Safety assessments include laboratory abnormalities, electrocardiograms, and echocardiograms. Adverse events will be graded according to NCI-CTCAE version 5.0.
from initial treatment until disease progression, death, loss to follow-up, or study completion，up to 3 years
Patient-Reported Outcomes
Time Frame: From initial treatment until disease progression or study completion ，up to 36 months
Change from baseline in quality of life scores.
From initial treatment until disease progression or study completion ，up to 36 months

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Correlation of Circulating Tumor Cells (CTCs) with Survival Outcomes
Time Frame: From initial treatment until disease progression or study completion ，up to 36 months.
Exploratory analysis to evaluate the correlation between circulating tumor cell (CTC) levels and survival prognosis.
From initial treatment until disease progression or study completion ，up to 36 months.
Molecular subtypes of breast cancer
Time Frame: Baseline (archival tumor tissue).
Exploratory analysis to evaluate Molecular subtypes of breast cancer patients confirmed by PAM50 testing.
Baseline (archival tumor tissue).

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Fudan University

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Hongxia Wang, Chief physician, Fudan University Principal Investigator Biyun Wang , Chief physician Fudan University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
February 12, 2025

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 30, 2028

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 30, 2029

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
November 26, 2025

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 28, 2026

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
May 29, 2026

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
May 29, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 28, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
November 1, 2025

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • DIAMOND

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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