Earlier today, Merrimack Pharmaceuticals, Inc., announced the initiation of a global, open-label, randomized Phase II trial of MM-302, a HER2-targeted nanoliposomal encapsulation of doxorubicin, in combination with trastuzumab (Herceptin®, Genentech/Roche) in patients with HER2-positive locally advanced or metastatic breast cancer.  The trial was designed with input from the U.S. Food and Drug Administration (FDA) to support a potential accelerated approval application.

“While there have been new therapies approved in the HER2-positive setting, there is no standard of care for patients whose cancer progresses despite treatment with trastuzumab, T-DM1 and pertuzumab.  In our experience to date, MM-302 has shown promising clinical activity and an acceptable safety profile in patients with metastatic breast cancer who have progressed on HER2-directed therapies.  We are moving this trial forward with a goal of transforming the standard of care for this population,” said Thomas Wickham, Ph.D., Vice President of Development and MM-302 Project Team Leader.

MM-302 is a novel antibody-drug conjugated liposomal doxorubicin (an anthracycline chemotherapy) that targets and binds to HER2, a protein that when overexpressed can lead to the development and aggressive progression of breast cancer.

As a liposomal encapsulation of doxorubicin, MM-302 is designed to allow for the selective uptake of drug into tumor cells while limiting exposure to healthy tissues, such as those of the heart.

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The company is pursuing this study based on encouraging results from an ongoing Phase I study showing a median progression free survival or PFS benefit of 5.7 months in a heavily pretreated (median of 4 prior lines of therapy) population of 47 patients receiving a therapeutic dose of MM-302 (30 mg/m2 or greater) alone or in combination with trastuzumab.  Patients who had not received prior anthracycline-based chemotherapy treatment had a median PFS of 10.9 months and a 35% overall response rate.  The most common adverse events in the Phase I study were fatigue, nausea and decreased appetite.  Cardiac events, which is a side effect that has limited the use of anthracyclines, have been infrequent and none were serious adverse events (3 out of 47 patients or 6% experienced declines in ejection fraction).

The HERMIONE trial is expected to enroll approximately 250 patients who will be randomized (1:1) to receive either MM-302 and trastuzumab or chemotherapy of their physician’s choice (capecitabine, gemcitabine or vinorelbine) and trastuzumab.  Eligible patients for the HERMIONE trial must have received prior treatment with trastuzumab in any setting, and pertuzumab (Perjeta®, Genentech/Roche) and ado-trastuzumab emtansine (T-DM1, Kadcyla®, Genentech/Roche) in the locally advanced or metastatic setting, but have not been treated with an anthracycline-based regimen.  The primary endpoint of the trial is PFS.  Secondary endpoints include overall survival, objective response rate, safety and tolerability.  

MM-302 is the second nanoliposomal product candidate in Merrimack’s clinical pipeline, the first being MM-398.

Published in: Merrimack Pharmaceuticals Inc. website

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