Dalpiciclib in Combination With Exemestane and Trastuzumab Plus Pyrotinib in Early Triple Positive Breast Cancer

Phase II Open-label, Multicentre, Exploratory Trial of Neoadjuvant Dalpiciclib in Combination With Exemestane and Trastuzumab Plus Pyrotinib in Early Triple Positive Breast Cancer

This is a phase II open-label, multicenter trial assessing the efficacy of combination regimen"Dalpiciclib plus Exemestane plus trastuzumab plus pyrotinib"in early triple positive breast cancer patients.

This is a phase II open-label, multicenter trial. The study assesses the treatment of patients with ER-positive /HER2 positive early breast cancer with neoadjuvant Dalpiciclib in Combination With Exemestane and Trastuzumab plus Pyrotinib. Patients were treated with intravenous trastuzumab (8 mg/kg loading dose followed by 6 mg/kg, Q3W) for six cycles plus oral Dalpiciclib (125 mg QD x 21，Q4W) and Exemestane (25 mg po QD ）and oral pyrotinib (320 mg po QD) for 20 weeks. The primary endpoints was pathological complete response.

Inclusion Criteria:

• 18 Years to 75 Years
• Newly diagnosed clinical stage II or III ER+/HER2+ breast cancer, staging criteria is to be based on AJCC 7.
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
• Primary tumor must have positive estrogen receptor (ER) ≥10%
• Primary tumor must be HER2-positive (IHC 3+ or FISH/CISH amplification)
• Baseline LVEF ≥50% measured by Echocardiography (preferred) or MUGA scan
• Normal organ and marrow function
• Written Informed Consent (IC) must be signed and dated by the patient and the Investigator prior to randomization.
• Baseline corrected QT interval (QTcF) < 480 ms
• All patients must be female.

Exclusion Criteria:

• Inflammatory breast cancer
• Evidence of bilateral invasive breast cancer or metastatic disease
• Received any prior treatment for primary invasive breast cancer
• Pregnant or lactating women
• Abnormal baseline hematological values:
• Abnormal baseline liver function, bilirubin, creatinine and/or INR (international normalized ratio)
• Subjects with known infection with HIV, HBV, HCV
• Other investigational drugs while on study
• Severe or uncontrolled hypertension, history of congestive heart failure or severe coronary arterial disease.
• Subjects assessed by the investigator to be unable or unwilling to comply with the requirements of the protocol