We are developing ZEN-3694 for the treatment of Malignant Peripheral Nerve Sheath Tumors (MPNST), a highly aggressive, rare cancer with very poor prognosis and no effective approved therapies.
About MPNST
MPNST is a rare type of soft tissue sarcoma that is often diagnosed in young to middle-aged adults affecting the protective sheath that covers peripheral nerves. MPNST makes up approximately 5-10% of all soft tissue sarcomas. An oncogene called Neurofibromatosis type 1 (NF1) is amplified in about 50% of patients driving progression of the disease.
MPNST Incidence
MPNST is a very rare aggressive form of soft tissue sarcoma with approximately 200 cases diagnosed annually in the US. MPNST is more common in individuals with an amplification of the NF1 oncogene with about 10% developing MPNST in their lifetime. MPNST typically occurs in young adults (20-50 years).
MPNST Diagnosis
Diagnosing MPNST can be challenging due to rarity, heterogeneous presentation, and resemblance to other soft tissue sarcomas. MPNST is diagnosed by a combination of clinical evaluation, imaging, and histopathological characterization of a tumor tissue biopsy.
MPNST Prognosis
MPNST is an aggressive disease with a 5-year survival rate ranging from 40-60%. Survival for patients with metastatic disease that does not respond to initial treatment is less than 10%. Prognosis may be influenced by several factors including tumor grade, size, and location, surgical resectability, extent of metastasis, and NF1 status.
MPNST Treatment
The primary treatment for localized MPNST is surgical resection with wide negative margins. Radiation and chemotherapy or a combination of these approaches may also be used. However, there are no FDA approved treatments for metastatic disease. There is a great clinical need for the development of effective combination therapies for the treatment of MPNST.
BET Inhibitors and MPNST
NF1, the oncogene that drives tumor growth in 50% of MPNST cases, can be targeted by a BET inhibitor such as ZEN-3694. We have provided ZEN-3694 for MPNST patients on a compassionate use basis, and several have experienced clinical benefit. Our company plans to develop its BET inhibitor ZEN-3694 in combination with other drugs to provide therapeutic options for patients with this difficult to treat form of cancer.
