A Two-Arm Study to Evaluate the Pharmacokinetics, Efficacy, and Safety of Subcutaneous Administration of the Fixed-Dose Combination of Pertuzumab and Trastuzumab in Combination With Chemotherapy in Chinese Participants With HER2-Positive Early Breast Cancer
Condition: HER2-positive Early Breast Cancer
MeSH terms: Breast Neoplasms
Intervention: Pertuzumab IV; Trastuzumab IV; Pertuzumab and Trastuzumab FDC SC; Doxorubicin; Cyclophosphamide; Docetaxel; Surgery; Post-Operative Radiotherapy; Hormone Therapy
Intervention description: Pertuzumab will be administered as a fixed non-weight-based loading dose of 840-milligrams (mg) IV and then a 420-mg IV maintenance dose Q3W.; Trastuzumab will be administered as an 8-milligram per kilogram of body weight (mg/kg) IV loading dose and then 6 mg/kg IV maintenance dose Q3W.; The pertuzumab and trastuzumab fixed-dose combination for subcutaneous administration (PH FDC SC) will be administered SC at a fixed non-weight-based dose. A loading dose of 1200 mg SC pertuzumab and 600 mg SC trastuzumab is then followed by a maintenance dose of 600 mg SC pertuzumab and 600 mg SC trastuzumab Q3W.; Doxorubicin 60 milligrams per meter squared of body surface area (mg/m^2) will be administered IV on Day 1 of each cycle of treatment (as part of AC Q3W) for Cycles 1-4.; Cyclophosphamide 600 mg/m^2 will be administered IV on Day 1 of each cycle of treatment (as part of AC Q3W) for Cycles 1-4.; Docetaxel 75 mg/m^2 will be administered IV on Day 1 of Cycle 5. At the investigator's discretion the dose may be escalated to 100 mg/m^2 IV for Cycles 6-8 (Q3W) provided no dose-limiting toxicity occurs.; Participants in both cohorts are scheduled to undergo surgery after 8 cycles of neoadjuvant therapy. Participants may undergo breast-conserving surgery or mastectomy according to routine clinical practice.; If indicated, radiotherapy is given after chemotherapy and surgery, during adjuvant HER2-targeted therapy and hormone therapy (for hormone-receptor positive disease).; For hormone receptor positive breast cancer, tamoxifen or aromatase inhibitors will be allowed as adjuvant hormone therapy for postmenopausal participants and with ovarian suppression or ablation for premenopausal participants in countries where it has been registered for this indication. Its use must be consistent with the registered label. Hormone therapy is given after chemotherapy and surgery during adjuvant HER2-targeted therapy.
Intervention MeSH terms: Cyclophosphamide; Docetaxel; Doxorubicin; Trastuzumab; Pertuzumab; Hormones
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 200.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This study will evaluate the pharmacokinetics, efficacy, and safety of the pertuzumab and
      trastuzumab fixed-dose combination for subcutaneous administration (PH FDC SC) as compared
      with those of the pertuzumab intravenous (IV) and trastuzumab IV formulations in Chinese
      participants with human epidermal growth factor receptor 2 (HER2)-positive early breast
      cancer.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Ability to comply with the study protocol, in the investigator's judgment

          -  Eastern Cooperative Oncology Group (ECOG) Performance Status greater or equal to (≤)1

          -  Stage II-IIIC (T2-T4 plus any N, or any T plus N1-3, M0), locally advanced,
             inflammatory, or early-stage, unilateral, and histologically confirmed invasive breast
             cancer

          -  Primary tumor greater than (>)2 centimeters (cm) in diameter, or node-positive disease
             (clinically or on imaging, and node positivity confirmed with cytology and/or
             histopathology)

          -  Human Epidermal Growth Factor Receptor 2 (HER2)-positive breast cancer confirmed by a
             central laboratory prior to study enrollment. HER2-positive status will be determined
             based on pretreatment breast biopsy material and defined as 3+ by immunohistochemistry
             (IHC) and/or positive by HER2 amplification by in situ hybridization (ISH) with a
             ratio of ≥2 for the number of HER2 gene copies to the number of signals for chromosome
             17 copies

          -  Hormone receptor status of the primary tumor, centrally confirmed

          -  Patient agreement to undergo mastectomy or breast conserving surgery after neoadjuvant
             therapy

          -  Availability of formalin-fixed, paraffin-embedded (FFPE) tumor tissue for central
             confirmation of HER2, hormone receptor status, and PIK3CA mutational analyses

          -  Baseline left ventricular ejection fraction (LVEF) ≥55% measured by echocardiogram
             (ECHO) or multiple-gated acquisition scan (MUGA)

          -  For women of childbearing potential (WOCBP) who are sexually active: agreement to
             remain abstinent (refrain from heterosexual intercourse) or use one highly effective
             non-hormonal contraceptive method with a failure rate of less than (<)1% per year, or
             two effective non-hormonal contraceptive methods during the treatment period and for 7
             months after the last dose of HER2-targeted therapy, and agreement to refrain from
             donating eggs during this same period

          -  For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use
             a condom in combination with a spermicidal foam, gel, film, cream, or suppository, and
             agreement to refrain from donating sperm, as specified in the protocol

          -  A negative serum pregnancy test must be available prior to randomization for WOCBP
             (premenopausal women and women <12 months after the onset of menopause), unless they
             have undergone surgical sterilization (removal of ovaries and/or uterus)

          -  No major surgical procedure unrelated to breast cancer within 28 days prior to
             randomization or anticipation of the need for major surgery during the course of study
             treatment

        Exclusion Criteria:

          -  Stage IV (metastatic) breast cancer

          -  History of invasive breast cancer

          -  History of concurrent or previously treated non-breast malignancies except for
             appropriately treated 1) non-melanoma skin cancer and/or 2) in situ carcinomas,
             including cervix, colon, and skin

          -  Have received any previous systemic therapy (including chemotherapy, immunotherapy,
             HER2-targeted agents, endocrine therapy [selective estrogen receptor modulators,
             aromatase inhibitors], and antitumor vaccines) for treatment or prevention of breast
             cancer, or radiation therapy for treatment of cancer

          -  Have a past history of ductal carcinoma in situ (DCIS) or lobular carcinoma in situ
             (LCIS) if they have received any systemic therapy for its treatment or radiation
             therapy to the ipsilateral breast

          -  High-risk for breast cancer and have received chemopreventative drugs in the past

          -  Multicentric (multiple tumors involving more than one quadrant) breast cancer, unless
             all tumors are HER2-positive

          -  Bilateral breast cancer

          -  Have undergone an excisional biopsy of primary tumor and/or axillary lymph nodes

          -  Axillary lymph node dissection (ALND) prior to initiation of neoadjuvant therapy

          -  Sentinel lymph node biopsy (SLNB) prior to neoadjuvant therapy

          -  Treatment with any investigational drug within 28 days prior to randomization

          -  Serious cardiac illness or medical conditions

          -  Inadequate bone marrow function

          -  Impaired liver function

          -  Inadequate renal function with serum creatinine >1.5X upper limit of normal (ULN)

          -  Current severe, uncontrolled systemic disease that may interfere with planned
             treatment (e.g., clinically significant cardiovascular, pulmonary, or metabolic
             disease; wound-healing disorders)

          -  Pregnant or breastfeeding, or intending to become pregnant during the study or within
             7 months after the last dose of HER2-targeted therapy

          -  Any serious medical condition or abnormality in clinical laboratory tests that, in the
             investigator's judgment, precludes the patient's safe participation in and completion
             of the study

          -  Known active liver disease, for example, active viral hepatitis infection (i.e.,
             hepatitis B or hepatitis C), autoimmune hepatic disorders, or sclerosing cholangitis

          -  Concurrent, serious, uncontrolled infections, or known infection with HIV

          -  Known hypersensitivity to study drugs, excipients, and/or murine proteins

          -  Current chronic daily treatment with corticosteroids (dose >10 milligrams [mg]
             methylprednisolone or equivalent excluding inhaled steroids)

          -  History of other malignancy within 5 years prior to screening, except for
             appropriately treated carcinoma in situ of the cervix, colon, skin, and/or
             non-melanoma skin carcinoma

          -  History of ventricular dysrhythmias or risk factors for ventricular dysrhythmias, such
             as structural heart disease (e.g., severe LVSD, left ventricular hypertrophy),
             coronary heart disease (symptomatic or with ischemia demonstrated by diagnostic
             testing), clinically significant electrolyte abnormalities (e.g., hypokalemia,
             hypomagnesemia, hypocalcemia), or family history of sudden unexplained death or long
             QT syndrome