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

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

Sponsors

Lead Sponsor: Caigang Liu

Collaborator: NovoCodex Biopharmaceuticals Co., Ltd.
Jiangsu HengRui Medicine Co., Ltd.

Source Shengjing Hospital
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.

Overall Status Recruiting
Start Date 2022-05-23
Completion Date 2026-12-30
Primary Completion Date 2025-12-30
Phase Phase 2/Phase 3
Study Type Interventional
Primary Outcome
Measure Time Frame
Total pathological complete response rate (tpCR) in percentage 3 years
Secondary Outcome
Measure Time Frame
Total breast pathological complete remission rate (bpCR) in percentage 3 years
Residual tumor burden (RCB) classification in grades 3 years
Best overall response rate (BORR) in percentage 3 years
Five-year overall survival (OS) 5 years
Disease-free survival (DFS) 3 years
Adverse events (AE) 3 years
Enrollment 150
Condition
Intervention

Intervention Type: Drug

Intervention Name: ARX788

Description: HER2 antibody-drug conjugate

Arm Group Label: ARX788 + pyrotinib maleate

Intervention Type: Drug

Intervention Name: Pyrotinib maleate

Description: EGFR/HER2 dual inhibitor

Arm Group Label: ARX788 + pyrotinib maleate

Intervention Type: Drug

Intervention Name: Trastuzumab

Description: anti-Her2 monoclonal antibody

Arm Group Label: trastuzumab + pertuzumab + docetaxel + carboplatin

Other Name: Herceptin

Intervention Type: Drug

Intervention Name: Pertuzumab

Description: anti-HER2 monoclonal antibody

Arm Group Label: trastuzumab + pertuzumab + docetaxel + carboplatin

Other Name: Perjeta

Intervention Type: Drug

Intervention Name: Docetaxel

Description: Cytotoxic chemotherapy

Arm Group Label: trastuzumab + pertuzumab + docetaxel + carboplatin

Intervention Type: Drug

Intervention Name: Carboplatin

Description: Cytotoxic chemotherapy

Arm Group Label: trastuzumab + pertuzumab + docetaxel + carboplatin

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;

Gender:

Female

Minimum Age:

18 Years

Maximum Age:

75 Years

Healthy Volunteers:

No

Overall Official
Last Name Role Affiliation
Caigang Liu, MD Principal Investigator Shengjing Hospital
Overall Contact

Last Name: Nan Niu, MD

Phone: 86-18940256668

Email: [email protected]

Location
Facility: Status: Contact: Investigator: Shengjing Hospital affiliated to China Medical University Nan Liu, MD 86-18940256668 [email protected] Caigang Liu, MD Principal Investigator
Location Countries

China

Verification Date

2022-06-01

Responsible Party

Type: Sponsor-Investigator

Investigator Affiliation: Shengjing Hospital

Investigator Full Name: Caigang Liu

Investigator Title: Director of the Cancer Center

Keywords
Has Expanded Access No
Condition Browse
Number Of Arms 2
Arm Group

Label: ARX788 + pyrotinib maleate

Type: Experimental

Description: ARX788 1.5 mg/kg intravenously (IV) every three weeks plus pyrotinib maleate 320 mg orally once daily for 6 cycles

Label: trastuzumab + pertuzumab + docetaxel + carboplatin

Type: Active Comparator

Description: Trastuzumab (8 mg/kg first dose, followed 6 mg/kg) puls pertuzumab (840 mg first dose, followed 420 mg) plus docetaxel (75 mg/m3) plus carboplatin (AUC6) IV every 3 weeks for 6 cycles

Patient Data No
Study Design Info

Allocation: Randomized

Intervention Model: Parallel Assignment

Primary Purpose: Treatment

Masking: None (Open Label)

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