Combining Pyrotinib and ARX788 for treating HER2-positive breast cancer

Efficacy and Safety of Pyrotinib Maleate Combined With ARX788 Neoadjuvant Treatment in Stage II-III HER2-positive Breast Cancer Patients Who Have Poor Outcomes After Treatment With Trastuzumab and Pertuzumab

This study is testing a new combination of two drugs, pyrotinib and ARX788, to see if it can help women with stage II-III HER2-positive breast cancer who haven't responded well to other treatments.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 30 (estimated)
• Ages: 18 Years to 75 Years
• Sex: Female
• Sponsor: Shengjing Hospital (Academic / other)
• Drugs / interventions: trastuzumab, pertuzumab, pyrotinib, radiation
• Locations: 1 site (Shenyang, Liaoning)
• Trial ID: NCT04983121 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the effectiveness and safety of combining pyrotinib maleate with ARX788 as a neoadjuvant treatment for stage II-III HER2-positive breast cancer patients who have shown poor response to previous therapies with trastuzumab and pertuzumab. The study is designed as a single-arm, multi-center, open-label trial, enrolling 30 female patients aged 18 to 75. Participants will receive the combined treatment to assess its impact on tumor response and safety. The trial aims to provide insights into a new therapeutic approach for patients with limited treatment options.

Who should consider this trial

Good fit: Ideal candidates are female patients aged 18 to 75 with stage II-III HER2-positive breast cancer who have previously undergone neoadjuvant therapy with trastuzumab and pertuzumab.

Not a fit: Patients with early-stage HER2-negative breast cancer or those who have not received prior neoadjuvant therapy may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could offer a new effective option for patients with HER2-positive breast cancer who have not responded well to existing therapies.

How similar studies have performed: While this approach is novel, previous studies have shown promising results with HER2-targeted therapies, indicating potential for success.

Eligibility criteria

Inclusion Criteria:

* Female patients aged ≥ 18 but ≤ 75 years (The maximal age of the subjects enrolled in the Phase 3 study of pyrotinib is 75 years old, and there is no safety data for the use of the drug in older people);
* Diagnosis of breast cancer meets the following criteria: Histologically confirmed invasive breast cancer; Tumor staging: Stage II-III patients who meet the 8th edition of AJCC Cancer Staging Manual; Patients who have undergone neoadjuvant therapy with trastuzumab and pertuzumab and have been assessed as SD (an increase of 0-20%), PD, inoperable or failing to meet the breast-conserving requirements; Failing to meet the breast-conserving requirements is defined as not meeting the following criteria: tumor size of T1 and T2 stage, proper breast volume, proper tumor-to-breast volume ratio, and able to maintain a good breast shape after surgery.
* HER2-positive breast cancer pathologically confirmed is defined as Immunohistochemical method (IHC3+) or FISH+;
* Eastern Cooperative Oncology Group (ECOG) level 0-1;
* The functional level of major organs must conform to the following requirements: Neutrophils (ANC) ≥ 1.5×109/L (with no use of growth factors within 14 days); Platelet count (PLT) ≥ 100×109/L (with no correct treatment within 7 days ); Hemoglobin (Hb) ≥ 90 g/L (with no correct treatment within 7 days ); Total bilirubin (TBIL) ≤ 1.5×upper limit of normal (ULN); Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3×ULN; Urea nitrogen and creatinine ≤ 1.5×ULN and creatinine clearance ≥ 50 mL/min (Cockcroft-Gault formula); Cardiac color Doppler ultrasound: left ventricular ejection fraction (LVEF) ≥ 50%; 12-lead electrocardiogram: QT interval ≤ 480 ms;
* Able to receive needle biopsy;
* Patients who participate in the trial voluntarily, sign an informed consent, have good compliance and are willing to comply with the follow-up visit.

Exclusion Criteria:

* Patients who are concurrently receiving other anti-tumor therapy;
* Bilateral breast cancer, inflammatory breast cancer, or occult breast cancer;
* With a history of any malignancies other than breast cancer in the past 5 years, excluding cured cervical carcinoma in situ, non-melanoma skin cancer or other malignant tumors;
* Inability to swallow, chronic diarrhea and intestinal obstruction, and having many factors that affect drug administration and absorption;
* Cardiac insufficiency, including but not limited to congestive heart failure, transmural myocardial infarction, angina pectoris requiring medical treatment, clinically significant valvular disease and high-risk arrhythmia, or abnormal QTc in the ECG examination during the screening period (at rest, QTc \> 450 ms in male or QTc \> 470 ms in female after correction of ECG examination);
* Uncontrolled hypertension (at rest, systolic blood pressure \> 160 mmHg or diastolic blood pressure \> 100 mmHg);
* Patients who are suffering severe or uncontrolled systemic diseases, such as unstable or uncompensable respiratory, heart, liver, or kidney diseases, as per the investigator's judgments;
* Female patients during pregnancy and lactation, or those who are fertile and positive for baseline pregnancy test or those of childbearing age who are unwilling to take effective contraceptive measures throughout the trial period;
* Serious concomitant diseases or other comorbid diseases that will endanger the safety of patients or interfere with the completion of the trial, including but not limited to severe hypertension, severe diabetes mellitus, and active infections that are out of control;
* Patients with known allergies to any active ingredients or excipients of ARX788, or with a history of protein drug allergy, a history of specific allergies (asthma, rheumatism, eczematous dermatitis), or a history of other severe allergic reactions, who are unsuitable for ARX788 treatment as per the investigator's judgments;
* With a history of interstitial pulmonary disease, drug-induced pulmonary interstitial disease, and radiation pneumonitis that require hormone therapy, or any clinically active pulmonary interstitial disease as suggested by any evidence;
* Patients who are currently suffering from keratitis, corneal disease, retinal disease, or active eye infection that require any interventions for the eyes.

Where this trial is running

Shenyang, Liaoning

• Shengjing Hospital affiliated to China Medical University — Shenyang, Liaoning, China (Recruiting)

Study contacts

• Principal investigator: Cai-Gang Liu — Department of Breast Surgery, Shengjing Hospital affiliated to China Medical University
• Study coordinator: Nan Niu, MD

Conditions Breast Neoplasms; Breast cancer; Pyrotinib; Neoadjuvant treatment