TESARO, Inc., an oncology-focused biopharmaceutical company, has  successfully achieved primary endpoint in two phase III trials of rolapitant, an investigational neurokinin-1 (NK-1) receptor antagonist in development for the prevention of chemotherapy-induced nausea and vomiting (CINV). The achievement in each trial and preparations are ongoing in support of a New Drug Application (NDA) submission for oral rolapitant to the US FDA.

"Despite the availability of preventative therapies and established treatment guidelines for CINV, a significant number of cancer patients still suffer from the debilitating side effects of delayed nausea and vomiting," said Mary Lynne Hedley, Ph.D., president of TESARO. "We are enthusiastic about the potential for this product candidate, with a profile that may include an extended half life, convenient, single-dose oral and intravenous formulations and a lack of CYP3A4-mediated drug interactions."

The first phase III study of rolapitant was an international, multicenter, randomized, double-blind, active-controlled study that enrolled 1,369 cancer patients receiving moderately emetogenic chemotherapy (MEC), approximately half of whom were receiving anthracycline-based treatment for breast cancer. Patients were randomized to receive either control, which consisted of a 5-HT3 receptor antagonist plus dexamethasone, or 200 milligrams of oral rolapitant plus control. The rolapitant arm successfully achieved statistical significance over the control arm for the primary endpoint of complete response (CR), defined as no vomiting and no use of rescue medication, in the delayed phase (the 24 to 120 hour period following initiation of chemotherapy). A greater proportion of patients treated with rolapitant in this trial achieved a CR in the acute and overall phases and experienced no significant nausea compared to the control arm, although statistical significance was not met for these secondary endpoints.

The second phase III study of rolapitant was an international, multicenter, randomized, double-blind, active-controlled study that enrolled 555 patients receiving highly emetogenic chemotherapy (HEC), defined as regimens which contain cisplatin at a dose equal to or greater than 60 mg/m2. Patients were randomized to receive either control, which consisted of 5-HT3 receptor antagonist plus dexamethasone, or 200 milligrams of oral rolapitant plus control. Similar to the MEC study, the rolapitant arm in the HEC study successfully achieved statistical significance over the control arm for the primary endpoint of CR in the delayed phase of CINV. A greater proportion of patients treated with rolapitant in this trial achieved a CR in the acute and overall phases and experienced no significant nausea compared to the control arm, although statistical significance was not met for these secondary endpoints.

Safety and tolerability data for patients who received rolapitant were similar to the results for those who received control, and were consistent with earlier clinical studies. The most frequently observed adverse events were balanced across treatment arms and included fatigue, alopecia and loss of appetite.

TESARO continues to enroll patients receiving HEC in a third and final phase III trial of rolapitant, and preparations in support of a mid-2014 NDA submission for oral rolapitant are ongoing. Full analyses of data from all three rolapitant pivotal phase III trials will be submitted for presentation at a future medical meeting.

Rolapitant is an investigational agent and, as such, has not been approved by the US FDA or any regulatory agencies.