A Multicenter, Randomized, Double-blind, Parallel-controlled Clinical 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.
Overview
- Phase
- Phase 3
- Intervention
- TQB2440 injection + Trastuzumab + Docetaxel
- Conditions
- HER2-positive Breast Cancer
- Sponsor
- Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
- Enrollment
- 412
- Locations
- 6
- Primary Endpoint
- Overall pathological complete response (tpCR) rate assessed by Independent review committee (IRC).
- Status
- Active, not recruiting
- Last Updated
- 2 years ago
Overview
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •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):
Exclusion Criteria
- •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);
Arms & Interventions
TQB2440 injection + Trastuzumab + docetaxel
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.
Intervention: TQB2440 injection + Trastuzumab + Docetaxel
Perjeta® + Trastuzumab + docetaxel
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.
Intervention: Perjeta + Trastuzumab + Docetaxel
Outcomes
Primary Outcomes
Overall pathological complete response (tpCR) rate assessed by Independent review committee (IRC).
Time Frame: Baseline up to 4 months.
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.
Secondary Outcomes
- Objective remission rate (ORR)(Baseline up to 2 years.)
- bpCR assessed by IRC.(Baseline up to 4 months.)
- Event-free survival (EFS)(Baseline up to two years.)
- tpCR rate evaluated by the investigators.(Baseline up to 4 months.)
- Disease free survival (DFS)(Baseline up to 2 years.)
- Breast conservation rate(Baseline up to 5 months.)
- Overall Survival (OS)(Baseline up to 2 years.)
- Breast pathological complete response (bpCR) rate evaluated by the investigators.(Baseline up to 4 months.)
- Incidence of adverse events(Baseline up to 2 years.)