STM 434 is a soluble receptor fused to part of an antibody that blocks the growth factor activin-A.
STM 434 is being studied in ovarian cancer and other advanced solid tumors.
Ovarian cancer is a disease that leads to 125,000 deaths a year, including 15,000 in the United States, making it the deadliest form of cancer for women. The levels of the transforming growth factor activin-A are elevated in patients with ovarian cancer.
We are investigating whether STM 434 can change the course of ovarian tumor growth by blocking the action of activin-A. Our preclinical studies have demonstrated that activin-A inhibitors can reduce ovarian tumor growth, complement the benefits of concurrent chemotherapy and improve survival in mice. At the 2013 annual meeting of the American Society of Clinical Oncology, we presented data showing that activin-A inhibitors, in combination with chemotherapy, worked better than chemotherapy alone in a mouse model of ovarian cancer.
Other Advanced Solid Tumors
We are also investigating STM 434 in several advanced solid tumors. Preclinical studies with our activin-A inhibitors have demonstrated improved survival in mouse models of advanced cancer.
Mechanism of Action
Activin-A is a growth factor that may play a role in regulating proliferation, migration, and survival of cancer stem cells in a number of malignancies. In ovarian cancer, activin-A regulates the ovaries’ physical processes and ability to produce tumors. In addition, overexpression of activin-A, a common feature in many ovarian cancers, promotes ovarian tumor proliferation and invasion. In preclinical testing, our activin-A inhibitors showed reductions in the growth of ovarian tumors of several different types. We will now test STM 434 in a clinical trial in ovarian cancer and other advanced solid tumors.
John Lu, Christopher M. Haqq, HQ Han. Effects of a soluble activin type 2B receptor Fc fusion protein (STM 217) in TOV-21G, a mouse xenograft model of clear cell ovarian cancer. Journal of Clinical Oncology 2013; 31 (supplement; abstract 2541). (Abstract)
Zhou X, Wang JL, Lu J, Song Y, Kwak KS, Jiao Q, et al. Reversal of cancer cachexia and muscle wasting by ActRIIB antagonism leads to prolonged survival. Cell. 2010;142 (4):531-43. (Abstract)