Combining Dalpiciclib and Pyrotinib for HER2-positive Advanced Breast Cancer

Treatment of Dalpiciclib Combined With Pyrotinib for Trastuzumab-sensitive HER2+ Advanced Breast Cancer: a Single Arm, Dual Cohort, Prospective, Open Phase II Exploratory Study

This study is testing a new combination of two medications, Dalpiciclib and Pyrotinib, to see if they can help people with advanced HER2-positive breast cancer who haven't had success with other treatments.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 120 (estimated)
• Ages: 18 Years and up
• Sex: Female
• Sponsor: Henan Cancer Hospital (Government)
• Drugs / interventions: trastuzumab, Neratinib, Lapatinib, pyrotinib, chemotherapy, patuzumab, pyrroltinib
• Locations: 1 site (Zhengzhou, Henan)
• Trial ID: NCT05328440 on ClinicalTrials.gov

What this trial studies

This clinical trial investigates the efficacy and safety of a combination regimen of Dalpiciclib Isethionate Tablets and Pyrotinib in treating HER2-positive metastatic breast cancer (MBC). The study focuses on patients with varying hormone receptor statuses and aims to leverage the synergistic effects of CDK4/6 inhibitors and anti-HER2 therapies. By targeting specific signaling pathways involved in breast cancer cell proliferation, the trial seeks to improve treatment outcomes for patients who have not responded to traditional therapies. The study is conducted in a controlled environment to ensure accurate assessment of the treatment's effectiveness.

Who should consider this trial

Good fit: Ideal candidates for this study are women aged 18 and older with non-resectable locally advanced or metastatic HER2-positive breast cancer.

Not a fit: Patients with HER2-negative breast cancer or those who have previously received adjuvant endocrine therapy may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a more effective option for patients with HER2-positive advanced breast cancer, potentially improving survival rates and quality of life.

How similar studies have performed: Other studies have shown promising results with similar combinations of CDK4/6 inhibitors and anti-HER2 therapies, indicating potential for success in this approach.

Eligibility 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.

Where this trial is running

Zhengzhou, Henan

• Henan Cancer Hospital — Zhengzhou, Henan, China (Recruiting)

Study contacts

• Principal investigator: Min Yan — Henan Cancer Hospital
• Study coordinator: Min Yan

Conditions Breast Neoplasms; HER2-positive MBC