a study of mk-2206 in combination with trastuzumab and lapatinib for the treatment of her2+ solid tumors (mk-2206-015)

Conditions: Advanced Solid Tumors; Breast Cancer

Summary: 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.

Eligibility criteria:
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.

Keywords: documented to be her2+