A Study of MK-2206 in Combination With Trastuzumab and Lapatinib for the Treatment of HER2+ Solid Tumors (MK-2206-015)

A Phase I Investigation of the Combination of MK-2206, Trastuzumab and Lapatinib in HER2+ Solid Tumors

This study will assess the safety, tolerability, and the maximum tolerated dose (MTD) of MK-2206 in combination with both trastuzumab and trastuzumab/lapatinib in participants with human epidermal growth factor receptor 2 positive (HER2+) breast cancer and other solid tumors. The primary hypothesis of this study is that the combination of oral MK-2206 with trastuzumab or with trastuzumab/lapatinib will be well tolerated in participants with advanced HER2+ solid tumors.

This study was divided into 2 parts. In Part 1, cohorts of 3 participants were to be enrolled sequentially on escalating doses of MK-2206 in combination with a fixed dose of trastuzumab. Barring dose-limiting toxicities (DLTs), additional participants were to be enrolled and dose-finding would proceed until an MTD was identified for MK-2206 when dosed either every other day (QOD) or once weekly (QW) in combination with trastuzumab. In Part 2, cohorts of 3 participants were to be enrolled sequentially on rising doses of lapatinib administered in combination with the MTD dose of MK-2206/trastuzumab established in Part 1. Barring DLTs, dose finding would proceed until an MTD of the 3-drug combination was identified.

Inclusion Criteria:

• Have a histologically or cytologically-confirmed locally advanced or metastatic HER2+ solid tumor.
• Have performance status ≤1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale.
• Have adequate organ function.
• Female participants have a negative pregnancy test 72 hours prior to receiving the first dose of study medication.
• Have completed any major surgery for a minimum of 28 days prior to enrollment in this study.
• Able to swallow tablets and has no surgical or anatomical condition that will preclude the patient from swallowing or absorbing oral medications on an ongoing basis.

Exclusion Criteria:

• Had chemotherapy, radiotherapy or biological therapy within 4 weeks of screening. Participants receiving trastuzumab and/or lapatinib prior to screening must be off both medications for 1 week prior to first dose of MK-2206 if trastuzumab had been administered at 2 mg/kg weekly and 3 weeks if trastuzumab had been administered at 6 mg/kg weekly.
• Currently participating or has participated in a study with an investigational compound or device within 30 days, or 5x half-life from prior agents, whichever is longer, of Day 1 of this study
• Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
• Has a primary CNS tumor.
• Has known hypersensitivity to the components of study drugs or its analogs.
• Has a history or evidence of heart disease.
• Has uncontrolled hypertension or diabetes.
• Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
• Is pregnant or breastfeeding or is expecting to conceive or father children during the study.
• Is HIV positive.
• Has symptomatic ascites or pleural effusion.
• Is receiving treatment with oral corticosteroids for reason other than CNS metastasis.