MM-121
MM-121/SAR256212 is a fully human monocolonal antibody that targets the HER3 receptor. Merrimack’s Network Biology approach identified HER3 as a critical tumorigenic node in several types of cancer. Heregulin-induced signaling of HER3 activates cellular pathways promoting the development, growth and progression of cancer. In addition, it is generally believed that HER3 activation serves as a compensatory mechanism by which cancer cells develop resistance to targeted therapies, many chemotherapies, and anti-hormonal therapies. MM-121 functions by inhibiting ligand-induced signaling through HER3 and activation of associated survival pathways. Our research suggests that combining MM-121 with other therapies could provide clinical benefit by:
- synergistically or additively attacking tumor growth, based on our preclinical research involving a broad range of combination therapies;
- delaying the development of resistance to other agents, based on research by us and others demonstrating that ErbB3 signaling is upregulated in response to treatment with other therapies; and
- restoring sensitivity to drugs, based on our preclinical research involving several cell types and xenograft models that are resistant to targeted therapies or chemotherapies.
We are investigating predictive biomarkers to identify patients that may benefit from MM-121 therapy.
MM-121 in the Clinic
MM-121 is currently being tested in a broad clinical development program in collaboration with Sanofi Oncology. This partnership investigates MM-121 in combination with several therapies across multiple patient populations. At this time there are several Phase 2 clinical trials spanning various patient populations including:
- Two trials in breast cancer in combination with either paclitaxel or exemestane;
- One trial in ovarian cancer in combination with paclitaxel; and
- One trial in lung cancer in combination with erlotinib.
In these studies, we are assessing the anti-tumor activity of the MM-121 combinations as well as the potential of MM-121 to reverse or delay resistance to the combination therapy being tested. We are also working to identify the underlying biological factors that determine the effectiveness to the therapy. These innovative study designs provide us with an opportunity to increase our understanding of cancer and identify those patients that are most likely to respond to therapy. We also continue to assess MM-121 as a combination therapy with other agents in multiple ongoing Phase 1 studies.
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