Merrimack Pharmaceuticals, Inc. announced that the US Food and Drug Administration (FDA) has granted seribantumab, also known as MM-121, Fast Track designation for development in patients with heregulin-positive, locally advanced or metastatic non-small cell lung cancer (NSCLC) whose disease has progressed following immunotherapy.

Fast Track is a program designed by the FDA to facilitate and expedite the development and review of drugs that treat serious conditions and fill an unmet medical need. Merrimack is conducting the SHERLOC trial, a global clinical study of seribantumab in combination with docetaxel or pemetrexed in heregulin-positive patients with NSCLC that is designed to support a Biologics License Application to the FDA. Seribantumab is Merrimack's wholly owned, fully human monoclonal antibody that targets ErbB3.

"We are pleased that the FDA recognizes the importance of investigating a novel, biomarker-directed agent such as seribantumab for patients with locally advanced or metastatic NSCLC who have been previously treated with an immunotherapy," said Dr. Akos Czibere, vice president, clinical development at Merrimack. "Heregulin-positive cancer cells are characterized by their ability to escape the effects of a broad range of cancer therapies and potentially contribute to accelerated disease progression. The SHERLOC trial is designed to advance the development of a much-needed treatment option for patients with heregulin-positive NSCLC after they progress on immunotherapies. This is important because we find that more than 50% of patients with NSCLC are heregulin-positive."

Heregulin-positive disease has been linked to rapid progression and poor prognosis in multiple types of cancer, including NSCLC. The higher the prevalence of heregulin-positive cancer cells in a tumor, the lower the anti-tumor effect of the chemotherapy. Seribantumab is designed to block heregulin-driven signaling and enhance the anti-tumor effect of the chemotherapy. Data from Merrimack's prior clinical studies have shown that standard-of-care therapy may be more effective and result in improved patient outcomes when combined with seribantumab. Merrimack is investigating the efficacy and safety of seribantumab plus standard-of-care therapy in the SHERLOC trial.

Lung cancer is the leading cause of cancer-related death in the United States. The American Cancer Society estimates that approximately 224,000 new cases of lung cancer (both small cell lung cancer and NSCLC) will be reported in 2016, 83% of which will be NSCLCi. Merrimack estimates that approximately 101,000 U.S. NSCLC patients will have heregulin-positive tumors, based on the prevalence seen in data presented by Merrimack at the 2014 European Society for Medical Oncology Congressii.

The SHERLOC trial is a randomized, open-label, multi-center, phase 2 study in patients with heregulin-positive, locally advanced or metastatic NSCLC. Merrimack expects to enroll approximately 280 heregulin-positive patients who will be randomized (2:1) to receive seribantumab in combination with either docetaxel or pemetrexed versus docetaxel or pemetrexed alone. Patients will be screened for heregulin status using a fully validated RNA-ISH assay (in situ hybridization). Eligible patients for the study must have failed prior treatment with no more than three lines of therapy including prior anti-PD-1 or anti-PD-L1 immunotherapy. The study's primary endpoint is overall survival with secondary endpoints including progression free survival, objective response rate, safety and quality of life measures. The study is designed to support a Biologics License Application to the FDA with data expected in 2018.

Seribantumab is Merrimack's wholly owned, fully human anti-ErbB3 monoclonal antibody that targets phenotypically distinct heregulin-positive cancer cells within solid tumors. Heregulin-positive cancer cells are characterized by their ability to escape the effects of targeted, cytotoxic and anti-endocrine therapies and potentially contribute to rapid clinical progression in patients whose tumor cells test positive for heregulin as detected by RNA-ISH. When used in the combination setting, seribantumab is designed to block the heregulin/ErbB3 signaling axis in order to make these cells accessible to the effects of the combination therapy and potentially lead to significantly improved clinical outcomes.

Merrimack is also developing its novel heregulin assay for seribantumab into a kit for commercial use under a partnership agreement with Leica Biosystems.