First-line Treatment of Dalpiciclib Combined With Pyrotinib for HER2+ Advanced Breast Cancer(DAP-Her-02)

• Status: Not yet recruiting
• Trial end date: 2026-01-01
• Target enrollment: 0
• Participant gender: Female

Summary

Based on different HR status, we explored the efficacy and safety of Pyrotinib and Dalpiciclib Isethionate Tablets based combination regimen in the first-line treatment of HER2 + MBC.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Henan Cancer Hospital
• Collaborator: Jiangsu HengRui Medicine Co., Ltd.
• Treatments: Fulvestrant; Trastuzumab

Criteria

Inclusion Criteria:

1. Premenopausal / perimenopausal / postmenopausal women who aged ≥ 18 years

2. Suffering from non resectable locally advanced recurrent breast cancer or metastatic breast cancer

3. group A: Women who have breast cancer histopathologically confirmed by positive estrogen receptor (ER; >10%), positive progesterone receptor (PR; >1%), and positive human epidermal growth factor receptor 2 (HER2) according to the 2018 American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) human epidermal growth factor receptor 2 (HER2) guideline. The pathological laboratory confirmed that the immunohistochemical (IHC) score was 3 +, or 2 +, and the in situ hybridization (ISH) test was positive (ISH amplification rate ≥ 2.0); (New) the end of trastuzumab treatment in the adjuvant treatment stage > 12 months, recurrence and metastasis, or no trastuzumab treatment in the early stage; No adjuvant endocrine therapy or postoperative adjuvant endocrine therapy > 24 months; Premenopausal or perimenopausal patients need to be combined with ofs (OFS includes bilateral ovariectomy or GnRHa drugs); group B: Women who have breast cancer histopathologically confirmed by negative estrogen receptor (ER), negative progesterone receptor (PR; <1%), and positive human epidermal growth factor receptor 2 (HER2) according to the 2018 American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) human epidermal growth factor receptor 2 (HER2) guideline. The pathological laboratory confirmed that the immunohistochemical (IHC) score was 3 +, or 2 +, and the in situ hybridization (ISH) test was positive (ISH amplification rate ≥ 2.0); (New) the end of trastuzumab treatment in the adjuvant treatment stage > 12 months, recurrence and metastasis, or no trastuzumab treatment in the early stage;

4. No previous systematic treatment for advanced diseases

5. at least one measurable lesion or only bone metastasis according to RECIST 1.1.

6. Eastern Cooperative Oncology Group (ECOG) performance status 0～1.

7. The patient must be able to swallow oral drugs

8. The functional level of organs must meet the following requirements:

a) Bone marrow function i) Absolute neutrophil count（ANC）≥1.5×109/L (no use of growth factor within 14 days) ii) Platelet count（PLT）≥100×109/L (no corrective treatment within 7 days) iii) Hemoglobin level（Hb）≥100 g/L (no corrective treatment within 7 days) b) Liver and kidney function i) Total bilirubin（TBIL）≤1.5 upper limit of normal value (ULN) ii) Alanine transaminase (ALT) and aspartate transaminase (AST) ≤3×ULN iii) Blood urea nitrogen (BUN) and creatinine ≤1.5×ULN and creatinine clearance≥50 mL/min (Cockcroft-Gault formula); c) Color Doppler echocardiography: Left ventricular ejection fraction ≥50% d) 12-lead electrocardiography: QTc interval ≤480 ms

9. Volunteers to participate in the study, provision of signed informed consent, good compliance and willingness to cooperate with follow-ups.

Exclusion Criteria:

1. Patients with symptomatic brain metastasis;

2. Unable to swallow, chronic diarrhea and intestinal obstruction, there are many factors affecting drug use and absorption;

3. patient who received radiotherapy, chemotherapy, surgery (excluding local puncture) or molecular targeted therapy within 4 weeks before admission; those who received anti-tumor endocrine therapy after screening period;

4. Participated in other drug clinical trials within 4 weeks before admission;

5. Tyrosine kinase inhibitors targeting HER2 (Neratinib, Lapatinib, pyrotinib, etc.) have been used or are being used in the past;

6. Patients previously treated with any CDK4 / 6 inhibitor;

7. Those who have other malignant tumors (with the exception of healed cervical carcinoma in situ) occurring in the past 5 years;

8. Those who are known to have a history of allergy to the component of study drugs; those who have a history of immunodeficiency, including positive detection of human immunodeficiency virus, hepatitis C virus, active hepatitis B or other acquired, congenital immunodeficiency diseases, or organ transplantation;

9. Those who had suffered from any heart disease, including arrhythmia which requires drug treatment or is of clinical significance; myocardial infarction; heart failure; and any other heart disease judged by the investigator as unsuitable for this trial;

10. Pregnant and lactating women; fertile women who provide positive results of baseline pregnancy test; women of childbearing age who are unwilling to take effective contraceptive measures during the whole study period;

11. If the accompanying diseases (including, but not limited to, severe hypertension, severe diabetes, and active infection, which cannot be controlled by drugs) that would be a potential hazard to participant's health, or affect the completion of the study as per investigator's judgement;

12. Moderate infection occurs within 4 weeks before the first administration (e.g. intravenous drip of antibiotics, antifungal or antiviral drugs according to clinical criteria), fever（> 38.5 ℃） of unknown origin occurs during the screening period/before the first administration.

13. A clear history of neurological or psychiatric disorders, including epilepsy or dementia.

14. Researchers believe that patients are not suitable for any other situation in this study.