Clinical Study to Evaluate the Efficacy and Safety of TQB2440 Injection/Perjeta® Combined With Trastuzumab and Docetaxel in the Treatment of Patients With Early or Locally Advanced Breast Cancer.

NCT05985187 | Unknown Phase 3

• 1 other identifier: TQB2440-III-01
• Study Type: interventional
• Target: 412
• Locations: 1 country
• Sites: 6

Brief Summary

This is a multicenter, randomized, double-blind, parallel-controlled Phase III study to evaluate the efficacy and safety of TQB2440 injection/Perjeta® combined with trastuzumab and docetaxel in patients with early or locally advanced ER/ PR-negative HER2-positive breast cancer. The trial is scheduled to enroll 412 participants. The sample size was estimated based on 20 treatment cycles and 6 recurrence visits.

Conditions

HER2-positive Breast Cancer

Outcome Measures

Primary Outcomes (1)

• Overall pathological complete response (tpCR) rate assessed by Independent review committee (IRC).

  Percentage of subjects with tumor shrinkage reached a complete response assessed by the IRC, defined as no invasive tumor cells in breast and axilla after primary tumor resection.

  Baseline up to 4 months.

Secondary Outcomes (9)

• tpCR rate evaluated by the investigators.

  Baseline up to 4 months.

• Breast pathological complete response (bpCR) rate evaluated by the investigators.

  Baseline up to 4 months.

• bpCR assessed by IRC.

  Baseline up to 4 months.

• Breast conservation rate

  Baseline up to 5 months.

• Objective remission rate (ORR)

  Baseline up to 2 years.

Study Arms (2)

TQB2440 injection + Trastuzumab + docetaxel

EXPERIMENTAL

Neoadjuvant phase (cycle 1-4): TQB2440 injection + Trastuzumab + Docetaxel, intravenous infusion on the first day of each cycle, each cycle is 21 days. Adjuvant chemotherapy phase (cycle 5-7): Fluorouracil (600 mg/m2)+Epirubicin (90 mg/m2)+Cyclophosphamide (600mg/m2), intravenous injection once a day, on the first day of each cycle, each cycle is 21 days. Double targeted maintenance phase (cycle 8-20): TQB2440 injection+Trastuzumab, intravenous infusion on the first day of each cycle, each cycle is 21 days.

Drug: TQB2440 injection + Trastuzumab + Docetaxel

Perjeta® + Trastuzumab + docetaxel

ACTIVE COMPARATOR

Neoadjuvant phase (cycle 1-4): Perjeta® (Pertuzumab injection) + Trastuzumab + Docetaxel, intravenous infusion on the first day of each cycle, each cycle is 21 days. Adjuvant chemotherapy phase (cycle 5-7): Fluorouracil (600 mg/m2)+Epirubicin (90 mg/m2)+Cyclophosphamide (600mg/m2), intravenous injection once a day, on the first day of each cycle, each cycle is 21 days. Double targeted maintenance phase (cycle 8-20): TQB2440 injection+Trastuzumab, intravenous infusion on the first day of each cycle, each cycle is 21 days.

Drug: Perjeta + Trastuzumab + Docetaxel

Interventions

TQB2440 injection + Trastuzumab + Docetaxel DRUG

TQB2440 injection is a biosimilar of Perjeta® (Pertuzumab injection) developed by Chia Tai Tianqing Pharmaceutical Group. Trastuzumab is a recombinant DNA-derived human IgG monoclonal antibody against P185 glycoprotein regulated by HER2 gene in cell nucleus. Docetaxel is a selective L-type calcium channel blocker. Fluorouracil + epirubicin + cyclophosphamide for 3 cycles is a routine chemotherapy method after neoadjuvant surgery for breast cancer. The combination of Pertuzumab and Trastuzumab will enhance the antitumor activity and is used as the double targeted maintenance.

TQB2440 injection + Trastuzumab + docetaxel

Perjeta + Trastuzumab + Docetaxel DRUG

Perjeta® with the general name Pertuzumab injection, is a recombinant humanized monoclonal antibody targeting the extracellular second domain of human epidermal growth factor receptor 2 (HER2). Trastuzumab is a recombinant DNA-derived human IgG monoclonal antibody against P185 glycoprotein regulated by HER2 gene in cell nucleus. Docetaxel is a selective L-type calcium channel blocker. Fluorouracil + epirubicin + cyclophosphamide for 3 cycles is a routine chemotherapy method after neoadjuvant surgery for breast cancer. The combination of Pertuzumab and Trastuzumab will enhance the antitumor activity and is used as the double targeted maintenance.

Perjeta® + Trastuzumab + docetaxel

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• The subjects voluntarily joined the study, signed the informed consent, and the compliance was good;
• Age: 18-75 years old (when signing the informed consent form); Eastern Cooperative Oncology Group Physical condition scoring criteria score: 0-1; Survival is expected to exceed 3 months;
• Patients with primary breast cancer confirmed by histopathology or cytology；
• Primary tumor diameter \> 2 cm measured by local standard assessment method, or lymph node positive lesions confirmed by clinical or imaging examination;
• The investigators determined that this was consistent with the American Joint Committee on Cancer (AJCC) 8th Edition of breast cancer Tumor Node Metastasis stage II-III C (T2-T4 plus any N, or any T plus N1-3, M0) and histologically proven invasive breast cancer. A patient with invasive breast cancer must have a solid lesion capable of coarse needle biopsy;
• Laboratory tests confirmed HER2 positive, defined as a 3+ immunohistochemical result or a positive Fluorescence in situ hybridization double probe (2018 edition of American Society of Clinical Oncology/College of American Pathologists HER2 Testing Guidelines)
• The confirmed estrogen receptor (ER) and progesterone receptor (PgR) were negative;
• The patient agrees to undergo a mastectomy when surgical criteria are met after neoadjuvant therapy;
• Major organs function well, meeting the following criteria:
• Blood routine test criteria (no blood transfusion within 7 days prior to screening, no hematopoietic stimulant drug correction):
• Hemoglobin (HGB) ≥90g/L;
• Neutrophil absolute value (NEUT) ≥1.5×10\^9/L;
• Platelet count (PLT) ≥ 100×10\^9/L;
• Leukocyte ≥2.5×10\^9/L;
• Biochemical tests must meet the following criteria:

You may not qualify if:

• Patients with stage IV metastatic breast cancer or other cancers that investigators determined could not be radically removed by neoadjuvant therapy;
• Bilateral invasive breast cancer;
• Patients with breast cancer who have previously received anti-tumor therapy, such as chemotherapy, endocrine therapy or anti-HER2 biotherapy, or who have undergone breast surgery (other than diagnostic biopsies for primary breast cancer);
• Occurred or present with other malignant tumors within 3 years. Patients with the following two conditions can be enrolled: other malignancies treated with a single operation, achieving continuous 5-year disease-free survival (DFS); Cured cervical carcinoma in situ, non-melanoma skin cancer and superficial bladder tumors \[Ta (non-invasive tumor), Tis (cancer in situ) and T1 (tumor infiltrating basal membrane)\];
• Major surgical treatment, open biopsy, or significant traumatic injury (except for diagnostic biopsies for primary breast cancer) received within 28 days before the start of study treatment;
• A wound or fracture that has not healed for a long time.
• Arteriovenous thrombosis occurred within 6 months, such as cerebrovascular accident (including temporary ischemic attack, cerebral hemorrhage, cerebral infarction), deep vein thrombosis and pulmonary embolism;
• Subject who have a history of psychotropic substance abuse and are unable to abstain or have mental disorders;
• Subjects with any severe and/or uncontrolled disease, including:
• Patients with a history of critical hypertension or hypertensive encephalopathy; Or uncontrolled high blood pressure (systolic blood pressure \>150 mmHg after taking antihypertensive drugs, or diastolic blood pressure \>100 mmHg);
• Heart failure or systolic dysfunction (LVEF \< 55%) diagnosis history;
• Have grade 2 myocardial ischemia or myocardial infarction, arrhythmia (including QTc ≥450 ms in men, QTc ≥470 ms in women, and grade 2 congestive heart failure (NYHA rating);
• Angina pectoris requiring treatment with anti-angina medication;
• Valvular heart disease of clinical significance;
• Screening period confirmed hepatitis C virus (HCV) positive, human immunodeficiency virus (HIV) positive, syphilis treponema specific antibody positive, HBsAg positive and peripheral blood hepatitis B virus DNA (HBV DNA) titer beyond the normal range;

Sponsors & Collaborators

• Chia Tai Tianqing Pharmaceutical Group Co., Ltd.: lead

Study Sites (6)

The First Affiliated Hospital of Chongqing Medical University

Chongqing, Chongqing Municipality, 400000, China

Location

Sun Yat-sen University Cancer Prevention Center

Guangzhou, Guangdong, 150001, China

Location

Affiliated cancer hospital of harbin medical university

Harbin, Heilongjiang, 150001, China

Location

The First Affiliated Hospital of PLA Air Force Medical University

Xi'an, Shaanxi, 710000, China

Location

The First Affiliated Hospital of Xi'an Jiaotong University

Xi'an, Shaanxi, 710000, China

Location

Tianjin Medical University Cancer Hospital

Tianjin, Tianjin Municipality, 300201, China

Location

Related Publications (1)

• Xu D, Wu J, Yu J, Yang Y, Wen X, Yang J, Wei H, Xu X, Li Y, Yang L, Wang L, Wang Y, Ma W, Li N. A historical controlled study of domestic trastuzumab and pertuzumab in combination with docetaxel for the neoadjuvant treatment of early HER2-positive breast cancer. Front Oncol. 2024 Feb 9;14:1281643. doi: 10.3389/fonc.2024.1281643. eCollection 2024.

  PMID: 38406813 DERIVED

MeSH Terms

Interventions

Trastuzumab; Docetaxel; pertuzumab

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 3, 2023
• First Posted: August 14, 2023
• Study Start: October 20, 2020
• Primary Completion: January 8, 2023
• Study Completion: December 1, 2023
• Last Updated: August 14, 2023

Record last verified: 2023-04

Locations

CN (6)