A Randomized Phase 2 Study of ARQ 197 Versus Investigator's Choice of Second-Line Chemotherapy in Patients With Locally Advanced or Metastatic Gastric Cancer Who Have Progressive Neoplastic Disease Following Treatment With One Prior Chemotherapy Regimen

This will be a multi-center, open-label randomized phase 2 study designed to evaluate the PFS of ARQ 197 versus investigator's choice of second-line chemotherapy in patients with unresectable (locally advanced or metastatic) gastric carcinoma who have progressive neoplastic disease following treatment with a prior regimen consisting of at least two of the drugs 5-FU, cisplatin and docetaxel. Patients will be randomized to ARQ 197 arm or investigator's choice arm in a 1:1 ratio. The study will also evaluate other efficacy and safety parameters including ORR, OS and adverse events in the two treatment arms.

Patients assigned to the investigator's choice arm may receive any one of the following:

• Oxaliplatin 85 mg/m2 i.v. every two weeks (each cycle = 4 weeks)
• Capecitabine 1250 mg/m2 p.o. twice daily for 14 days followed by 7 days of no therapy every 3 weeks (each cycle = 3 weeks)
• Irinotecan 125 mg/m2 i.v. weekly for 4 weeks followed by 2 weeks of no therapy every 6 weeks (each cycle = 6 weeks) Treatment will continue unless one of the treatment discontinuation criteria is met. Dose reductions should occur based on the current labels for each of the investigator choice agents.

Patients randomly assigned to the ARQ arm will receive 120 mg of ARQ 197 twice daily (240 mg/day) throughout the treatment period. The treatment of ARQ 197 can be continued until unacceptable toxicity, documented progression of disease, or another discontinuation criterion is met. A cycle of ARQ 197 treatment will be defined as 21 days and cycles may be repeated every 3 weeks (21 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.