Trial Information

A Randomized Phase 2 Study of ARQ 197 Versus Gemcitabine in Treatment-Naïve Patients With Unresectable Locally Advanced or Metastatic Pancreatic Adenocarcinoma

This is a multi-center, open-label randomized phase 2 study designed to evaluate the PFS of
treatment-naïve patients with unresectable (locally advanced or metastatic) pancreatic
adenocarcinoma following treatment with either ARQ 197 (ARQ arm) or gemcitabine alone (GEM
arm). The study will also evaluate other efficacy and safety parameters including ORR, OS
and adverse events in the two treatment arms. Patients randomly assigned to the GEM arm
will receive gemcitabine alone. Patients assigned to the ARQ arm will receive oral ARQ 197
alone.

ARQ 197 is an investigational oral drug supplied as capsules in multiple strengths. For the
study initial shipment the capsules were 120 mg each, 30 count. In the ARQ arm, patients
will take 120 mg of ARQ 197 twice daily, once in the morning and once in the evening one
hour prior to or two hours after a meal. ARQ 197 treatment will be continued until
unacceptable toxicity, documented progression of disease, or another discontinuation
criterion is met.

Gemcitabine is a commercially available drug for the treatment of patients with locally
advanced or metastatic adenocarcinoma of the pancreas. In the GEM arm, gemcitabine will be
administered by intravenous infusion over 30 minutes at a dose of 1000 mg/m2. The dosing
schedule of gemcitabine will be once weekly for the first cycle (4 weeks), then once weekly
for 3 consecutive weeks followed by a week of rest for each subsequent cycle. Gemcitabine
therapy will be continued until unacceptable toxicity, documented progression of disease, or
another discontinuation criterion is met.

A treatment cycle is defined as 28 days for both treatment arms. Cycles may be repeated
every 4 weeks (28 days) based on toxicity and response. The assigned treatment should
continue until unacceptable toxicity, disease progression (clinical or radiological) or
another discontinuation criterion is met.

Tumor evaluations: Tumor evaluations will be performed in 8-week intervals. Tumor response
(complete response, partial response, stable disease, progressive disease and ORR) will be
evaluated using Response Evaluation Criteria in Solid Tumors (RECIST).

Progression-free survival: The time of disease progression-free will be calculated from
randomization until disease progression per RECIST or death due to any cause. Patients who
are alive and progression free will be censored at the date of their last tumor evaluation.

Overall survival: Overall survival time will be calculated from the date of randomization
until death due to any cause.

Safety assessments: Data on vital signs, physical examination, adverse events, serum
chemistry, hematological laboratory tests, and electrocardiograms will be collected.

This study is designed to establish potential efficacy of ARQ 197 in treatment naive
pancreatic cancer patients in a controlled, randomized study. The sample size of 30
Evaluable patients per treatment group is considered adequate to provide meaningful
estimates of the PFS and ORR and OS rates, however, this study is not powered to show
statistically significant differences between the treatment groups. Therefore, the analyses
will be primarily descriptive in nature. Taking into account an anticipated
drop-out/loss-to-follow-up rate of 20%, the total sample size will be 72 patients.

Primary and secondary objectives will be analyzed in the two treatment arms using
appropriate patient populations and statistical methods.