Combination treatment for HR+/HER2+ breast cancer

Pyrotinib Combined With Trastuzumab, Dalpiciclibe and Letrozole for HR+/HER2+ Breast Cancer:A Single Arm, Open Label, Phase II Trial

This study is testing a new combination of four drugs to see if it helps people with certain types of breast cancer feel better and respond well to treatment.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 30 (estimated)
• Ages: 18 Years and up
• Sex: Female
• Sponsor: Yantai Yuhuangding Hospital (Academic / other)
• Drugs / interventions: immunotherapy, trastuzumab, pyrotinib, chemotherapy
• Locations: 1 site (Yantai, Shandong)
• Trial ID: NCT05800756 on ClinicalTrials.gov

What this trial studies

This phase 2 trial investigates the safety and biological effects of a combination therapy involving pyrotinib, trastuzumab, dalpiciclib, and letrozole in patients with stage II-III hormone receptor-positive and HER2-positive breast cancer. Operable patients will receive two cycles of the combination therapy, followed by imaging evaluations to assess their response. Those achieving a complete or partial response will continue with the original regimen, while others will switch to a different treatment plan. The study aims to evaluate the primary endpoint of pathological complete response rate and secondary endpoints including overall response rate and safety profile.

Who should consider this trial

Good fit: Ideal candidates are postmenopausal or premenopausal women aged 18 and older with confirmed invasive HR+/HER2+ breast cancer.

Not a fit: Patients with non-invasive breast cancer or those who do not meet the hormonal receptor positivity criteria may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could improve response rates and outcomes for patients with HR+/HER2+ breast cancer.

How similar studies have performed: Other studies have shown promising results with similar combination therapies in treating HR+/HER2+ breast cancer, indicating potential for success.

Eligibility criteria

Inclusion Criteria:

1. A ECOG PS score of 0-1;
2. Postmenopausal or pre menopausal/perimenopausal women aged ≥ 18 years who must receive LHRH agonists during the study period;
3. Pathological examination confirmed invasive breast cancer with positive ER, PR and HER 2;

(1)Follow the 2018 ASCO-CAP HER 2 positive interpretation guidelines. The pathology laboratory confirms that the immunohistochemical (IHC) score is 3+, or 2+and the in situ hybridization (ISH) test is positive; (2)ER positive was defined as the percentage of ER positive cells ≥ 10%; (3)The percentage of PR positive cells ≥ 10%; 4、The tumor stage is early (T2-3, N0-1, M0) or locally advanced (T2-3, N2-3, M0) patients with breast cancer newly treated; 5、The functions of main organs meet the following requirements (no blood transfusion, no use of whitening and platelet raising drugs within 2 weeks before screening):

1. Blood routine examination: neutrophil (ANC) ≥ 1.5 × 109/L； Platelet count (PLT) ≥ 90 × 109/L； Hemoglobin (Hb) ≥ 90g/L;
2. Blood biochemistry: total bilirubin (TBIL) ≤ 1.5 times the upper limit of normal value (ULN); Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 1.5 × ULN； Alkaline phosphatase ≤ 2.5 × ULN； Urea nitrogen (BUN) and creatinine (Cr) ≤ 1.5 × ULN；
3. Color Doppler echocardiography: left ventricular ejection fraction (LVEF) ≥ 55%; (4)12 lead ECG: Fridericia corrected QT interval (QTcF)\<470 msec. 6、Women who can accept biopsy; 7、Volunteered to participate in this study; signed informed consent; with good compliance and willingness to follow-up.

Exclusion Criteria:

1. Patients with stage IV breast cancer;
2. Inflammatory breast cancer;
3. Previous antineoplastic treatment or radiotherapy for any malignant tumor, excluding cured cervical carcinoma in situ, basal cell carcinoma or squamous cell carcinoma;
4. At the same time, he received anti-tumor therapy in other clinical trials, including endocrine therapy, bisphosphonate therapy or immunotherapy;
5. The patient had undergone major surgical procedures unrelated to breast cancer within 4 weeks before enrollment, or the patient has not completely recovered from such surgical procedures;
6. Serious heart disease or discomfort, including but not limited to the following diseases:

(1)History of diagnosis of heart failure or systolic dysfunction (LVEF\<50%); (2)High risk uncontrolled arrhythmia, such as atrial tachycardia, resting heart rate\>100 bpm, significant ventricular arrhythmia (such as ventricular tachycardia) or higher grade atrioventricular block (i.e. Mobitz Ⅱ second degree atrioventricular block or third degree atrioventricular block); (3)Angina pectoris requiring anti angina drugs; (4)Valvular heart disease with clinical significance; (5)ECG showed transmural myocardial infarction; (6)Poor control of hypertension (systolic blood pressure\>180mmHg and/or diastolic blood pressure\>100mmHg); 7、Inability to swallow, intestinal obstruction or other factors affecting drug administration and absorption; 8、People known to have a history of allergy to the drug components of this protocol; 9、Have a history of immunodeficiency, including HIV test positive, or other acquired or congenital immunodeficiency diseases, or have a history of organ transplantation; 10、Female patients during pregnancy and lactation, female patients with fertility and positive baseline pregnancy test, or patients of childbearing age who are unwilling to take effective contraceptive measures during the whole trial period and within 7 months after the last study drug use; 11、Those who have a history of abuse of psychotropic substances and cannot quit or have mental disorders; 12、Suffering from serious concomitant diseases or other conditions that may interfere with the planned treatment of concomitant diseases, or any other conditions that the investigator believes are not suitable for the patient to participate in this study.

Where this trial is running

Yantai, Shandong

• Yantai Yuhuangding Hospital — Yantai, Shandong, China (Recruiting)

Study contacts

• Principal investigator: Guangdong Qiao — Yantai Yuhuangding Hospital
• Study coordinator: Yizi Cong

Conditions Breast Cancer; breast cancer; CDK4/6 inhibitor; hormone receptor-positive; HER2 positive; dalpiciclib; pyrotinib