Plexxikon commences PLX3397 Phase 2 trial in patients with Hodgkin lymphoma

Plexxikon today announced that it has treated the first patient in a Phase 2 clinical trial in Hodgkin lymphoma with PLX3397. This novel agent is an oral, selective inhibitor that down-modulates two key cell types that are thought to mediate the progression of Hodgkin lymphoma tumors — macrophages and mast cells. The Phase 2 trial is one of several planned proof-of-concept trials to be initiated with PLX3397 in 2011.

The trial is a multi-center, single-arm trial expected to enroll approximately 30 patients with Hodgkin lymphoma who have relapsed or become refractory to standard therapies. Objectives of this trial include assessing the efficacy of orally administered PLX3397 as measured by overall response rate, as well as the duration of response, the disease control rate, progression-free survival, response biomarkers and overall safety. Additional information about the Phase 2 trial is available at www.clinicaltrials.gov.

Tumor-associated macrophages comprise a significant amount of the tumor bulk in Hodgkin lymphoma, and increased numbers are associated with a worse prognosis. Mast cells are also an important inflammatory cell type that can stimulate the tumor cells directly. In addition, over-expression of CSF-1, the primary ligand for the Fms receptor - one of the key targets of PLX3397 - has been demonstrated to stimulate growth of primary Hodgkin tumor cells; inhibition of Fms blocks the growth of these cells.

"PLX3397 is an important product candidate both for Plexxikon's growing oncology franchise and for our FMS portfolio. Since PLX3397 targets multiple facets of Hodgkin lymphoma pathology, we expect treatment benefits to include both tumor growth inhibition, and reduction of invasiveness and metastatic spread," said K. Peter Hirth, Ph.D., chief executive officer of Plexxikon. "In other cancers, we are hopeful about a variety of combination treatments since preclinical models have shown that PLX3397 can overcome chemotherapy- and radiation-resistance in tumors driven by increased levels of CSF-1, such as metastatic breast cancer. Additionally, we expect to see a reduction in metastases and tumor growth for cancers that metastasize to the bone; consequently we anticipate a reduction in cancer bone pain as well."