A Study of Trastuzumab Emtansine (Trastuzumab-MCC-DM1, T-DM1) in Combination With Pertuzumab Administered to Patients With Human Epidermal Growth Factor Receptor-2 (HER2)-Positive Locally Advanced or Metastatic Breast Cancer Who Have Previously Received Trastuzumab

There were 2 phases in the study, a Dose Escalation phase (Phase 1b) and a Dose Expansion phase (Phase 2a). In the Dose Escalation phase, 3 patients were enrolled at the first dose level (3.0 mg/kg trastuzumab emtansine) and and 6 patients were enrolled at the second dose level (3.6 mg/kg trastuzumab emtansine). An additional 58 patients were enrolled at the 3.6 mg/kg trastuzumab emtansine dose level in the Dose Expansion phase (Phase 2a) of the study.

Inclusion criteria

• Histologically documented human epidermal growth factor receptor 2 (HER2)-positive locally advanced or metastatic breast cancer.
• Tumor tissue blocks or 15-20 unstained tissue slides for confirmatory central laboratory HER2 status testing and other exploratory assessments.
• Prior trastuzumab in any line of therapy.
• No prior trastuzumab emtansine (T-DM1) or pertuzumab therapy.
• Measurable disease.
• For women of childbearing potential, agreement to use an effective form of contraception and to continue its use for the duration of the study.
• Life expectancy ≥ 90 days.

Exclusion criteria

• Less than 21 days since the last anti-tumor therapy, including chemotherapy, biologic, experimental, immune, hormonal, or radiotherapy for the treatment of breast cancer, with the following exceptions: Hormone-replacement therapy or oral contraceptives; palliative radiation therapy involving ≤ 25% of marrow-bearing bone if administered ≥ 14 days prior to first study treatment.
• History of intolerance or hypersensitivity to trastuzumab and/or adverse events related to trastuzumab that resulted in trastuzumab being permanently discontinued.
• Peripheral neuropathy of Grade ≥ 2.
• History of clinically significant cardiac dysfunction.
• Current severe, uncontrolled systemic disease, eg, clinically significant cardiovascular, pulmonary, or metabolic disease.
• Brain metastases that are untreated, progressive, or have required any type of therapy to control symptoms from brain metastases within 60 days of the first study treatment.
• History of other malignancy within the last 5 years, except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, or other malignancy with a similar expected curative outcome.