Trial Information

A Phase 2 Study of ARQ 197 in Patients With Microphthalmia Transcription Factor Associated Tumors

This is a multi-center, single arm, two-stage phase 2 study of ARQ 197 in patients with
microphthalmia transcription factor associated (MiT) tumors. ARQ 197 is a novel small
molecule drug designed to block the activity of c-Met, which is thought to play multiple key
roles in human cancer, including cancer cell growth, survival, angiogenesis, invasion and
metastasis.

The microphthalmia transcription factor tumors (MiT tumors) are clear cell sarcoma (CCS),
alveolar soft part sarcoma (ASPS), and translocation associated renal cell carcinoma (RCC).
These soft tissue cancers are characterized by a common transcriptional mechanism that leads
to inexorable spread and resistance to all known therapies. They tend to strike adolescents
and young adults, and are invariably fatal if not resectable at diagnosis. Several academic
laboratories have shown that genetic translocations in these tumors upregulate c-Met, and
that such tumors are dependent upon this activity.

The study will enroll adolescent (age 13 or older) and adult patients with a histologically
or cytologically confirmed MiT malignant disease. Eligible patients will receive ARQ 197
twice daily. Treatment will be continued until progression of disease, unacceptable
toxicity, or another discontinuation criterion is met.

During the study, tumor evaluations will be performed at baseline, then in 8-week intervals.

To evaluate each patient's safety and the drug's toxicity, physical examinations, laboratory
evaluations, vitals signs, and adverse event assessments will be performed throughout the
study. Blood samples for PK analysis will be collected during first cycle of treatment from
up to 10 patients aged 20 or younger. Archival tissue specimens and relevant laboratory
results on patients' gene translocation/fusion status will be collected.

Tumor biopsies may also be collected (optional) with patient's consent. If patients agree
tumor samples may be collected using core needle biopsy.

In addition, to explore biological responses of tumors to ARQ 197 treatment, FDG-PET
scanning will be performed at three time points: within 14 days prior to the treatment, on
Day 8 (± 2 days) of Cycle 1 and after two cycles of treatment coinciding with tumor
measurement.