Merrimack Pharma Reports Final Clinical Results for MM-302 Phase 1 Study

Merrimack Pharmaceuticals, Inc.

announced updated and final clinical results for the Phase 1 study of MM-302, a novel HER2-targeted liposomal doxorubicin, in HER2-positive metastatic breast cancer. The results were presented today by Patricia LoRusso, D.O., in a clinical trials plenary oral session at the 2015 American Association for Cancer Research (AACR) Annual Meeting in Philadelphia, PA. Data described the safety and promising clinical activity of MM-302 in patients with advanced HER2-positive metastatic breast cancer. Results from the trial showed that the group of patients (n=62) treated with 30 mg/m^2 or more of MM-302 alone, in combination with trastuzumab or with trastuzumab and cyclophosphamide, had a median progression free survival (mPFS) of 7.6 months (95% CI: 3.6-10.9 months) and an overall response rate (ORR) of 11%. Of note, 25 patients who had not been previously treated with anthracyclines had an mPFS of 11 months (95% CI: 1.8-13.1 months) and an ORR of 24%. "HER2-positive breast cancer affects approximately 20% of all breast cancer patients and represents a particularly aggressive form of breast cancer. Despite recent advancements in treatment, the vast majority of metastatic breast cancer patients will progress and have a high need for additional therapies," said Patricia LoRusso, D.O., professor of medicine in the Division of Oncology at Yale University. "We are encouraged by these data on the safety and promising clinical activity of MM-302 in patients who have exhausted many therapeutic options for their disease. Our results support the further evaluation of MM-302 in an anthracycline-naive population in the HERMIONE trial." The most frequent adverse events occurring in greater than 20% of the population in this Phase 1 study were constipation, cough, decreased appetite, diarrhea, dyspnea, fatigue, nausea, neutropenia, stomatitis and vomiting. The most common Grade 3/4 adverse event was neutropenia observed in 8 patients. Six out of 69 patients (9%) had protocol-defined asymptomatic declines in left ventricular ejection fraction (LVEF). In 1 of the 6 patients, this was reported as a Grade 1 cardiac failure that was possibly related to study treatment. "As an antibody-drug conjugate, MM-302 is designed to maximize targeted delivery to the tumor while trying to reduce the cardiotoxic effects of traditional anthracycline chemotherapies," said Thomas Wickham, Ph.D., Vice President of Development and MM-302 Project Team Leader. "The study population in this Phase 1 trial is heavily pre-treated, as the majority of patients have already progressed on a median of four prior therapies. We are encouraged by the 7.6 month median progression-free survival in this patient population and are looking forward to our next steps for the MM-302 clinical development program." Merrimack is currently enrolling the HERMIONE study that is designed to support a potential application for accelerated approval in the U.S. and conditional marketing authorization in the E.U. The HERMIONE study is for HER2-positive, metastatic breast cancer patients who are anthracycline-naive and have not been previously treated with pertuzumab and T-DM1-containing regimens. METHODOLOGY AND RESULTS A Phase 1 study of MM-302, a HER2-targeted PEGylated liposomal doxorubicin, in patients with HER2-positive metastatic breast cancer (mBC) Safety of MM-302 Data were presented on 69 patients treated in this Phase 1 trial. Patients received a median of 4 prior therapies for metastatic disease. Safety of MM-302 o Neutropenia was the most common Grade 3/4 adverse event occurring in 8 patients with 1 patient experiencing febrile neutropenia. The most frequent all-grade adverse events occurring in >20% of the population were constipation, cough, decreased appetite, diarrhea, dyspnea, fatigue, nausea, neutropenia, stomatitis and vomiting. o Protocol defined asymptomatic declines in left ventricle ejection fraction (LVEF) were observed in six patients; four of these patients had reversible declines consistent with trastuzumab-induced changes. One patient experienced two reversible asymptomatic LVEF declines (classified as a Grade 1 cardiac failure) that resulted in treatment discontinuation after receiving 11 cycles of MM-302 in combination with trastuzumab. o Patients treated with MM-302 as a monotherapy showed no signs of protocol-defined decline in cardiac function. o 11 of 69 patients received greater than 550 mg/m^2 of cumulative doxorubicin dose. Activity Data o Seven of the 62 patients treated with 30 mg/m^2 or more MM-302 alone, in combination with trastuzumab or with trastuzumab and cyclophosphamide had a clinical response to treatment resulting in an overall response rate (ORR) of 11%. o Overall, the median progression-free survival (mPFS) in patients treated with 30 mg/m^2 or more of MM-302 was 7.6 months (95% CI: 3.6-10.9 months). o An ORR of 24% and an 11 month mPFS (95% CI: 1.8-13.1 months) was observed in anthracycline-naive patients (n=25).