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.
• Age ≥ 18 years.
• 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.
• Hormone receptor status is known, based on the most recent pathological report.
• At least one measurable lesion meeting RECIST 1.1 criteria.
• 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.
• ECOG performance status of 0 to 1.
• 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%.
• 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.
• 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.
⁃ 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