A Dose-Finding Study of Subcutaneous Herceptin (Trastuzumab) in Healthy Male Volunteers and Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Females

This two-part study is designed to select the subcutaneous (SC) dose of Herceptin that results in comparable exposure to intravenous (IV) Herceptin in healthy male participants and in HER2-positive female participants. The study will also assess the safety and tolerability of the SC and IV formulations. In Part 1 of the study, four cohorts will be treated with a single dose of Herceptin as follows: Cohort 1 (6 milligrams per kilogram \[mg/kg\] IV in healthy male participants); Cohort 2 (6 mg/kg IV in HER2-positive female participants); Cohort 3 (6 mg/kg SC in healthy male participants); Cohort 4 (10 mg/kg SC in healthy male participants). An additional cohort of healthy volunteers (Cohort 5) will be opened if both SC dose levels from Cohorts 3 and 4 result in Herceptin exposures different from the target concentration produced by a single IV dose, or if the variability in pharmacokinetic (PK) parameter values cannot be used to define the target SC dose level. In Part 2 of the study, HER2-positive female participants will receive a single dose of SC Herceptin at the dose level defined in Part 1. Participants from Part 1 are eligible to enter Part 2 provided they receive the second (Part 2) study dose of Herceptin a minimum of 22 days after their first (Part 1) dose.

Sex

All

Minimum age

18 Years

Inclusion Criteria:

* Healthy Participants (Part 1 only)

  * Males 18 to 45 to years of age
  * Baseline left ventricular ejection fraction (LVEF) greater than (\>) 60 percent (%)
* HER2-Positive Females (Parts 1 and 2)

  * Females greater than or equal to (≥) 18 years of age
  * Eastern Cooperative Oncology Group (ECOG) performance status of 0
  * Previous non-metastatic operable primary invasive HER2-positive breast cancer
  * Baseline LVEF \>55%

Exclusion Criteria:

* Healthy Participants (Part 1 only)

  * Clinically significant abnormalities in laboratory test results or electrocardiogram
  * History of significant allergies, gastrointestinal, renal, hepatic, cardiovascular, or pulmonary disease
  * History of hypersensitivity or allergic reaction, spontaneous or following drug administration
  * History of cardiac conditions
* HER2-Positive Females (Parts 1 and 2)

  * Metastatic disease
  * Concurrent other malignancy requiring therapy of any modality which may interfere with PK investigations or result in unexpected toxicity
  * Use of Herceptin in previous 5 months
  * Serious cardiac illness

• DERIVEDWynne C, Harvey V, Schwabe C, Waaka D, McIntyre C, Bittner B. Comparison of subcutaneous and intravenous administration of trastuzumab: a phase I/Ib trial in healthy male volunteers and patients with HER2-positive breast cancer. J Clin Pharmacol. 2013 Feb;53(2):192-201. doi: 10.1177/0091270012436560. PMID 23436264