Merrimack Announces Final Clinical Results for MM-302 Phase 1 Study Demonstrating Robust Activity in Heavily Pre-Treated Patients with HER2-Positive Metastatic Breast Cancer

Median progression-free survival of 7.6 months reported for overall study population whose disease has progressed on a median of 4 prior therapies

Strong data observed in anthracycline-naive patient population; HERMIONE trial in support of a potential accelerated approval underway to further evaluate MM-302 activity

Apr 20, 2015, 16:01 ET from Merrimack Pharmaceuticals, Inc.

CAMBRIDGE, Mass., April 20, 2015 /PRNewswire/ -- Merrimack Pharmaceuticals, Inc. (Nasdaq: MACK) 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/m2 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 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

  • 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.
  • 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.
  • Patients treated with MM-302 as a monotherapy showed no signs of protocol-defined decline in cardiac function.
  • 11 of 69 patients received greater than 550 mg/m2 of cumulative doxorubicin dose.

Activity Data

  • Seven of the 62 patients treated with 30 mg/m2 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%.
  • Overall, the median progression-free survival (mPFS) in patients treated with 30 mg/m2 or more of MM-302 was 7.6 months (95% CI: 3.6-10.9 months).
  • An ORR of 24% and an 11 month mPFS (95% CI: 1.8-13.1 months) was observed in anthracycline-naive patients (n=25).

About Merrimack

Merrimack is a biopharmaceutical company discovering, developing and preparing to commercialize innovative medicines paired with companion diagnostics for the treatment of cancer. Merrimack seeks to gain a deeper understanding of underlying cancer biology through its systems biology-based approach and develop new insights, therapeutics and diagnostics to improve outcomes for cancer patients. Merrimack currently has multiple oncology therapeutics in clinical development and three additional candidates in late stage preclinical development. Merrimack's lead product candidate, MM-398, recently completed a Phase 3 clinical trial in post-gemcitabine pancreatic cancer. Based on the results of this clinical trial, Merrimack is currently preparing a New Drug Application for MM-398. For more information, please visit Merrimack's website at www.merrimackpharma.com or connect on Twitter at @MerrimackPharma.

Forward-Looking Statement

To the extent that statements contained in this press release are not descriptions of historical facts, they are forward-looking statements reflecting the current beliefs and expectations of management made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995, as amended. Forward-looking statements include any statements about Merrimack's strategy, future operations, future financial position and future expectations and plans and prospects for Merrimack, and any other statements containing the words "anticipate," "believe," "estimate," "expect," "intend," "may," "plan," "predict," "project," "target," "potential," "will," "would," "could," "should," "continue," and similar expressions. In this press release, Merrimack's forward-looking statements include statements about the potential effectiveness and tolerability of MM-302 as a monotherapy and in combination with trastuzumab with or without cyclophosphamide in certain patient populations or subpopulations, the potential for the HERMIONE trial to support an accelerated approval application to the FDA and its ability to translate clinical data into future clinical success. Such forward-looking statements involve substantial risks and uncertainties that could cause Merrimack's clinical development programs, future results, performance or achievements to differ significantly from those expressed or implied by the forward-looking statements. Such risks and uncertainties include, among others, the uncertainties inherent in the initiation of future clinical trials, availability of data from ongoing clinical trials, expectations for regulatory approvals and other matters that could affect the availability or commercial potential of Merrimack's drug candidates or companion diagnostics. Merrimack undertakes no obligation to update or revise any forward-looking statements. Forward-looking statements should not be relied upon as representing Merrimack's views as of any date subsequent to the date hereof. For a further description of the risks and uncertainties that could cause actual results to differ from those expressed in these forward-looking statements, as well as risks relating to Merrimack's business in general, see the "Risk Factors" section of Merrimack's Annual Report on Form 10-K filed with the Securities and Exchange Commission (SEC) on February 27, 2015 and other reports Merrimack files with the SEC.

CONTACT: Media Contacts: Debbie Tseng, Merrimack 617-441-7659 dtseng@merrimackpharma.com

Investor Contact: Geoffrey Grande, CFA Merrimack 617-441-7602 ggrande@merrimackpharma.com

SOURCE Merrimack Pharmaceuticals, Inc.



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