Phase II Clinical Trial Results of 'ADI-PEG 20' Show Efficacy in Human Metastatic Melanoma Deficient in a Key Metabolic Enzyme, and in Lymphomas in Preclinical Studies
(Antitumor effect shown in 63% of metastatic melanoma tumors that were negative for a specific enzyme, argininosuccinate synthetase (ASS(-)); enzyme also reported to be inactivated in human lymphomas). Results presented at ASCO Cancer Meeting, Chicago June 4-8, 2010
SAN DIEGO, June 7 /PRNewswire/ -- Physicians attending the
annual meeting of the American Society of Clinical Oncology (ASCO)
presented evidence that pegylated arginine deiminase (ADI-PEG 20),
a novel anticancer drug that targets ASS(-) tumors, and which is
being developed and manufactured by Polaris Group, was effective in
inhibiting the growth of metastatic melanoma cells. Dr. L.G. Feun
from the University of Miami, Miami, FL presented results from a
phase II trial in 36 metastatic melanoma patients who were treated
with ADI-PEG 20 weekly by intramuscular injection and who were
evaluable for response. Of the evaluable patients, 14/36 (39%) had
a tumor response and/or clinical benefit. For 16 patients with
ASS(-) tumors, 10/16 (63%) showed some evidence of antitumor
effect, while only 1/10 (10%) patients had stable disease when the
tumor was ASS(+). Polaris plans to initiate its first phase III
clinical trial with ADI-PEG 20 during 4Q 2010 in treating
hepatocellular carcinoma which has a high prevalence of ASS(-)
tumor cells.
A second study presented at the ASCO meeting by Dr. P.W.
Szlosarek from Barts Cancer Research UK Centre and colleagues from
other UK medical centers, assessed ASS expression in normal and
malignant lymphoid cell lines and tissues. Using several detection
methods and malignant and normal cell lines, a good correlation was
observed with absence of ASS in tumor cells but not in normal
cells. Notably, ASS protein was absent in >99% of lymphoma cells
as assessed by immunohistochemical staining. When these cell lines
were treated with ADI-PEG 20, the ASS(-) malignant lymphoma cells
displayed apoptotic effects and were inhibited in growth while the
normal lymphoblastoid ASS(+) cell lines and those in which ASS
could be induced, were resistant to the apoptotic effects of
ADI-PEG 20. "ASS(-) lymphomas are sensitive to arginine depletion
suggesting that this approach is worth exploring as a potential
novel therapeutic approach in the management of patients with
lymphoma," said Dr. Szlosarek.
ASS is required for the production of arginine, an amino acid
needed for growth and replication of cells. Normal tissue cells
have normal levels of ASS and can produce sufficient arginine for
their own growth and survival in the presence of ADI-PEG 20.
However, growth and replication of ASS-deficient tumor cells is
inhibited by ADI-PEG 20. This inhibition occurs because ADI-PEG 20
breaks down the circulating arginine that ASS-deficient tumor cells
rely upon. The studies presented at this year's annual ASCO meeting
provide convincing evidence that ADI-PEG 20 can inhibit growth of
metastatic melanoma cells and lymphomas along with other tumor
types that have been reported at other cancer meetings and in
scientific publications. Clinical studies in other human cancers
such as small cell lung cancer, mesothelioma, sarcoma and leukemia
are planned to begin in the near future.
Polaris Group, a multinational biopharmaceutical company, is
specialized in the research and development of new drugs to treat
cancer and other debilitating diseases in humans.
Source: Polaris Group
CONTACT: Jim Thomson of Polaris Group, JimThomson@polarispharma.com
Web Site: http://www.polarispharma.com/
Posted: June 2010
