Clinical TrialsSTM 434 is a soluble receptor fused to part of an antibody that is designed to block the growth factor Activin A. STM 434 is being studied in patients with ovarian cancer and other advanced solid tumors.
Ovarian cancer is the fifth leading cause of cancer death in women in the United States. According to the National Cancer Institute, there were an estimated 22,192 new ovarian cancer cases and 14,180 ovarian cancer deaths in the United States in 2015. Surgery and cytotoxic chemotherapies are widely used to treat ovarian cancer; however, the outcomes have changed little in 40 years. There were estimated to be approximately 192,500 women suffering from ovarian cancer in the United States in 2012. According to the American Cancer Society, based on patients diagnosed between 2005 and 2011, the blended five-year survival rate is only 45.6% for ovarian cancer patients overall. New therapies are needed to address this important issue in women’s health. Importantly, the levels of the transforming growth factor Activin A are elevated in patients with ovarian cancer, making this molecule an attractive target for novel therapeutic approaches.
We are investigating whether STM 434 can change the course of ovarian tumor growth by blocking the action of Activin A. Preclinical studies demonstrated that Activin A inhibitors can reduce ovarian tumor growth, complement the benefits of concurrent chemotherapy and improve survival in mice.
Other Advanced Solid Tumors
We are also investigating STM 434 in several advanced solid tumors many of which are known to overexpress Activin A. For example, preclinical studies with a surrogate of STM 434 have demonstrated improved survival in a mouse model of colon cancer.
Mechanism of Action
STM 434 is a ligand trap, which mimics the ActR2B receptor, binding Activin A and other ligands (such as activin B made by kidney tumors) that would otherwise activate this receptor promoting tumor proliferation or invasion.
Preclinical results in experiments blocking Activin A by using a soluble receptor, both as a single therapy and in combination with chemotherapy, led to a reduction in tumor size. In other experiments, mice with high Activin A levels, which caused granulosa cell ovarian tumors, survived longer after treatment with a surrogate for STM 434 in comparison to untreated mice.
Lu J, Haqq CM, Han HQ. 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. J Clin Oncol 2013; 31 (supplement; abstract 2541). (Citation)
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. (Citation)