Overview

Efficacy and Safety of Pyrotinib Maleate Combined With ARX788 Neoadjuvant Treatment in Breast Cancer Patients

Status:
Not yet recruiting
Trial end date:
2027-08-15
Target enrollment:
0
Participant gender:
Female
Summary
Next-generation Site-specific human epidermal growth factor receptor 2 (HER2)-targeting Antibody-drug Conjugate (ARX788) is an antibody-conjugated drug. Results from the phase I safety, tolerability and pharmacokinetic trial of ARX788 single drug in Chinese patients with advanced HER2 breast cancer indicated a good safety of the test drug, and responses to anti-tumor therapy were observed in the target dose group. Phase II clinical trial is being carried out gradually. This trial is designed to observe the effectiveness and safety of pyrotinib maleate combined with ARX788 neoadjuvant treatment in stage II-III HER2-positive breast cancer patients experiencing a poor efficacy of trastuzumab and pertuzumab.
Phase:
Phase 2
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
Shengjing Hospital
Treatments:
Antibodies
Immunoconjugates
Mitogens
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.