A Study of Trastuzumab Emtansine (T-DM1) in Combination With Docetaxel, and Potentially Pertuzumab, in Participants With Advanced Breast Cancer

An Open-Label, Multi-Center Phase I/II Study of the Safety and Tolerability of the Combination of Trastuzumab-MCC-DM1 (T-DM1) With Docetaxel, and Potentially Pertuzumab, for Treatment for Patients With Advanced Breast Cancer

This is an open-label, multi-center, non-randomized study of the safety and tolerability of the combination of T-DM1 plus docetaxel for the treatment of participants with metastatic breast cancer (MBC) and of T-DM1 plus docetaxel with or without pertuzumab, for the treatment of participants with locally advanced breast cancer (LABC). The study comprises an initial dose finding (feasibility) part to determine the maximum tolerated dose (MTD) of T-DM1 and docetaxel, followed by an extension part aiming to consolidate the safety and efficacy of the recommended docetaxel/T-DM1 combination regimen.

Inclusion Criteria:

• Eastern Cooperative Oncology Group (ECOG) performance status 0-1 (ECOG performance status of 2 will be allowed if only due to debilitating bone disease)
• HER2-positive metastatic or locally advanced breast cancer

For MBC participants:

• Documented metastatic or inoperable locally advanced (without meeting LABC criteria) disease, amenable for treatment with docetaxel
• History of disease progression within 3 months prior to study entry

For LABC participants:

• Newly diagnosed locally advanced breast cancer, Stage IIA-IIIC (American Joint Committee on Cancer [AJCC] staging system)

Exclusion Criteria:

• Significant cardiac disease
• Inadequate bone marrow, liver or renal function

For MBC participants:

• Participants must not have received radiotherapy for the treatment of metastatic or locally recurrent/advanced disease other than for the relief of pain in progressing metastatic bone lesions and/or brain metastases
• Brain metastases that are untreated, symptomatic or require therapy to control symptoms; or any radiation, surgery, or other therapy to control symptoms from brain metastasis within 2 months of the first study treatment.

For LABC participants:

• Clinically or radiologically detectable metastasis (M1 disease)
• Participants for whom surgery as primary intent procedure is the best option to treat their disease
• Participants must not have received any systemic or loco-regional anti-cancer therapy for the treatment of locally advanced disease