Phase IIIb Study to Evaluate the Safety and Tolerability of Herceptin SC With Perjeta and Docetaxel in Patients With HER2-positive Advanced Breast Cancer

Inclusion Criteria:

• Histologically or cytologically confirmed and documented adenocarcinoma of the breastwith metastatic or locally recurrent disease not amenable to curative resection.Patients with measurable and/or non-measurable disease evaluable according to ResponseEvaluation Criteria in Solid Tumors (RECIST), Version 1.1 are eligible.

• HER2-positive disease (defined as either immunohistochemistry [IHC] 3 + or in situhybridization [ISH] positive) as assessed by local laboratory on primary tumor ormetastatic site if primary tumor not available

• Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1

• Left ventricular ejection fraction (LVEF) of at least 50%

• Negative serum pregnancy test result at baseline and use of effective contraception asdefined by the protocol

Exclusion Criteria:

• Previous systemic non-hormonal anti-cancer therapy for the metastatic or locallyrecurrent disease. Note: Prior to study entry, up to two lines of hormonal therapy formetastatic or locally recurrent disease are permitted, one of which may be incombination with everolimus.

• Disease-free interval of less than 6 months from completion of adjuvant or neoadjuvantsystemic non-hormonal treatment to recurrence of breast cancer

• Previous approved or investigative anti-HER2 agents as neoadjuvant or adjuvant therapyfor any breast cancer treatment, except Herceptin

• History of persistent Grade 2 or higher hematological toxicity resulting from previousadjuvant or neoadjuvant therapy

• Radiographic evidence of central nervous system (CNS) metastases as assessed bycomputed tomography (CT) or magnetic resonance imaging (MRI), unless they have beentreated and have been stable for at least 3 months and do not require ongoingcorticosteroid treatment

• Current peripheral neuropathy of Grade 3 or greater

• History of other malignancy within the last 5 years prior to first dose of study drugadministration, except for carcinoma in situ of the cervix or basal cell carcinoma

• Inadequate organ function

• Uncontrolled hypertension with or without medication

• Clinically significant cardiovascular disease

• History of LVEF decline to below 50% during or after prior Herceptin neo-adjuvant oradjuvant therapy

• Current known infection with HIV, hepatitis B virus, or hepatitis C virus

• Severe uncontrolled concomitant disease that would contraindicate the use of any ofthe investigational drugs used in this study or that would put the patient at highrisk for treatment-related complications, including severe pulmonaryconditions/illness

• Pregnant or lactating women

• Dyspnea at rest due to complications of advanced malignancy or other disease requiringcontinuous oxygen therapy

• History of receiving any investigational treatment within 28 days prior to first doseof study drug administration (dosing) or concurrent participation in anyinterventional clinical trial