Confirmed tumor response in clear cell sarcoma leads to expanded trial
ArQule, Inc. (NASDAQ: ARQL) today announced the expansion of its Phase 2
trial with ARQ 197, a proprietary, orally administered small molecule
inhibitor of the c-Met receptor tyrosine kinase, in MiT (Microphthalmia
Transcription Factor)-associated tumors based on the achievement of a
partial response, as defined by RECIST (Response Evaluation Criteria in
Solid Tumors), in a patient with clear cell sarcoma.
“We are delighted to observe this first
objective response in a cohort of patients affected by a
molecularly-linked group of tumor types for which there is no effective
treatment,” said Paolo Pucci, chief executive
officer of ArQule. “We are especially pleased
for the patient, who is continuing on treatment. Based on the
achievement of the protocol-defined endpoint of an objective response in
the first stage of this trial, we are proceeding to the second stage,
optimizing it further by implementing a higher dose of ARQ 197, 360
milligrams (mg) twice daily (b.i.d.). In parallel, we are preparing to
initiate discussions with regulatory authorities to determine the
optimal clinical pathway to prove the utility of this compound in
sarcomas.”
MiT tumors, which include clear cell sarcoma (CCS), alveolar soft part
sarcoma (ASPS) and translocation-associated renal cell carcinoma (RCC),
are linked biologically through a common chromosomal abnormality that is
responsible for the over-expression of c-Met resulting in the
development of these tumors. Tumors with this abnormality are resistant
to current therapies and, in the absence of successful surgical
resection, are invariably fatal.
During the first stage of the study, 23 patients were enrolled and
treated with 120 mg of ARQ 197 b.i.d. To date, fourteen of these
patients are evaluable for efficacy. In addition to the patient with the
confirmed partial response, ten of the evaluable patients have
demonstrated stable disease. Preliminary data from the first stage will
be presented at the Connective Tissue Oncology Society meeting scheduled
in November, 2008.
“This objective clinical response builds upon
the strong pre-clinical rationale for this trial, including data which
showed that knockout of MiT expression by shRNA suppressed c-Met
expression and impeded the growth of human clear cell sarcoma cells in
vitro and in vivo,” said Dr. George
Demetri, Director of the Ludwig Center at the Dana-Farber/Harvard Cancer
Center, the clinical site leading this trial.
