On February 19, 2015 Merrimack Pharmaceuticals reported the initiation of a global, open-label, biomarker-selected, randomized Phase 2 clinical trial of MM-121, a fully human monoclonal antibody targeting ErbB3, in combination with docetaxel or pemetrexed versus docetaxel or pemetrexed alone in patients with heregulin positive, locally advanced or metastatic non-small cell lung cancer (Press release Merrimack, FEB 19, 2015, View Source [SID:1234501755]).

“This marks the first MM-121 trial we’ve initiated where only patients with a high heregulin biomarker profile will be enrolled into the study. It builds on our learnings from the previous MM-121 Phase 2 clinical trials we completed across lung, ovarian and breast cancers where we saw a clear trend of patients in those studies with this biomarker profile benefitting from combining MM-121 with standard therapies,” said Akos Czibere, MD, PhD, MM-121 Global Development Lead at Merrimack. “This study is a significant step toward preparing a registration trial of MM-121 in non-small cell lung cancer, and further supports Merrimack’s systems biology approach and its impact on drug discovery and development. We look forward to applying our clinical biomarker findings to future studies with MM-121 and ultimately improving outcomes in patients who no longer respond to standard-of-care therapies.”

MM-121 is Merrimack’s wholly owned, fully human monoclonal antibody that targets ErbB3, a cell surface receptor that is activated by the ligand heregulin. Heregulin-driven ErbB3 signaling has been implicated as a mechanism of tumor growth and resistance to targeted, cytotoxic and anti-endocrine therapies. When used in the combination setting, MM-121 is designed to block ErbB3 signaling in order to enhance the anti-tumor effect of a combination therapy partner. Merrimack is pursuing this study based on encouraging results from a broad MM-121 Phase 2 program which identified high heregulin levels as a potential prognostic factor of poor response to standard-of-care therapy across multiple cancers. The results also showed that patients with heregulin-high tumors experienced a longer time to progression when they received a combination of MM-121 with their standard-of-care therapy as compared to patients who received the standard therapy alone. Across the three different standard-of-care combination regimens, a consistent safety profile demonstrated a modest yet tolerable increase in adverse events.

As part of this trial, Merrimack expects to enroll approximately 120 heregulin positive patients that will be randomized (2:1) to receive either MM-121 plus the investigator’s choice of docetaxel or pemetrexed, or the investigator’s choice of docetaxel or pemetrexed alone. Eligible patients for the trial must have failed prior treatment with no more than two lines of therapy for locally advanced or metastatic disease. The primary endpoint of the trial is progression free survival (PFS). Secondary endpoints include overall survival, objective response rate, safety and tolerability. Merrimack plans to conduct the trial at sites in the United States, Canada and Europe. Initial trial sites located at the Horizon Oncology Center in Lafayette, Indiana and Northwestern Medicine Developmental Therapeutics Institute in Chicago, Illinois are now open to screen patients in the United States.