Plexxikon 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.”
