Clinical trial NCT05426486: A Study of ARX788 Combined With Pyrotinib Maleate Versus TCBHP (Trastuzumab Plus Pertuzumab With Docetaxel and Carboplatin) as Neoadjuvant Treatment in HER2-positive Breast Cancer Patients
Official title: A Randomized, Open Label, Multi-center Phase II-III Neoadjuvant Study Comparing the Efficacy and Safety of ARX788 Combined With Pyrotinib Maleate Versus TCBHP (Trastuzumab Plus Pertuzumab With Docetaxel and Carboplatin) in Patients With HER2-positive Breast Cancer
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
PHASE3
Conditions: HER2-positive Breast Cancer
Keywords: ARX788
Pyrotinib
HER2-positive Breast Cancer
Neoadjuvant
Lead sponsor: Shengjing Hospital
Sponsor class: OTHER
First posted: 2022-06-22
Enrollment: 136
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a randomized, open label Phase II-III neoadjuvant study comparing the efficacy and safety of ARX788 combined with pyrotinib maleate versus TCBHP (trastuzumab plus pertuzumab with docetaxel and carboplatin) in patients with HER2-positive breast cancer.

Detailed description: This is a randomized, open label Phase II-III neoadjuvant study comparing the efficacy and safety of ARX788 combined with pyrotinib maleate versus TCBHP (trastuzumab plus pertuzumab with docetaxel and carboplatin) in patients with HER2-positive breast cancer. Patients will be randomized (1:1) to one of the two treatment arms: arm 1, ARX788 plus pyrotinib maleate for 6 cycles; arm 2, trastuzumab plus pertuzumab with docetaxel and carboplatin for six cycles. Patients will undergo surgery after neoadjuvant therapy. Efficacy will be assessed every 2 cycles.

Eligibility criteria: Inclusion Criteria:

* Female patients aged ≥ 18 but ≤ 75 years;
* 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;
* HER2-positive breast cancer pathologically confirmed is defined as Immunohistochemical method (IHC 3+) or IHC 2+ with FISH+;
* Eastern Cooperative Oncology Group (ECOG) level 0-1;
* The functional level of major organs must conform to the following requirements: Neutrophils (ANC) ≥ 1.5×10\^9/L (with no use of growth factors within 14 days); Platelet count (PLT) ≥ 100×10\^9/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;
* 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:

* Previously received any anti-tumor therapy (chemotherapy, radiotherapy, molecular targeted therapy, endocrine therapy, etc.);
* Patients who are concurrently receiving other anti-tumor therapy;
* Bilateral breast cancer, inflammatory breast cancer, or occult breast cancer;
* Stage IV breast cancer;
* With a history of any malignancies other than breast cancer in the past 5 years, excluding cured cervical carcinoma in situ and melanoma skin cancer;
* Inability to swallow, chronic diarrhea and intestinal obstruction, and having many factors that affect drug administration and absorption;
* Patients with known allergies to any active ingredients or excipients of Investigational medicinal product;
* 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;
* Once suffered from any heart disease, including: (1) arrhythmia with clinical significance, (2) myocardial infarction; (3) heart failure; (4) investigator's judgment as not suitable for participating in this trial;
* 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;

Primary outcomes:
measure: Total pathological complete response rate (tpCR) rate
timeFrame: 3 years
Secondary outcomes:
measure: Breast pathological complete response rate (bpCR) rate
timeFrame: 3 years
measure: Residual tumor burden (RCB)
timeFrame: 3 years
measure: Best overall response rate (BORR)
timeFrame: 3 years
measure: Five-year overall survival (OS)
timeFrame: 5 years
measure: Event-free survival (EFS)
timeFrame: 3 years
measure: Adverse events (AE)
timeFrame: 3 years
Other outcomes:
Locations:
city: Shenyang
country: China
facility: Shengjing Hospital affiliated to China Medical University
state: Liaoning
Study officials:
affiliation: Shengjing Hospital
name: Caigang Liu, MD
role: PRINCIPAL_INVESTIGATOR
References: