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Colorectal Cancer Drug Tivantinib Fails Mid-Stage Trial

No additional benefit when added to irinotecan and cetuximab (Jan. 11)

A phase II clinical study of the colorectal cancer drug tivantinib (ARQ 197, ArQule/Daiichi Sankyo) failed to meet the trial’s primary endpoint of progression-free survival (PFS). PFS was 8.3 months in the tivantinib group versus 7.3 months in the control group, but the difference was not statistically significant.

In addition, tivantinib failed to provide a significant improvement in the objective response rate (ORR), a secondary endpoint. The ORR was 45% in the tivantinib arm versus 33% in the control arm.

The phase II trial involved 122 patients with unresectable colorectal cancer in the U.S., Russia, and Western Europe. All of the patients had progressed after first-line treatment and had tumors that expressed the wild-type form of the KRAS gene. The patients were randomly assigned to receive either tivantinib (360 mg twice daily) plus irinotecan and cetuximab, or placebo plus irinotecan and cetuximab. The primary objective of the trial was to assess the contribution of tivantinib to the irinotecan-plus-cetuximab treatment regimen.

Adverse events were reported at similar rates in the tivantinib and control arms, except for increased neutropenia observed in the tivantinib arm.

Tivantinib is an orally administered selective inhibitor of MET, a receptor tyrosine kinase. In certain healthy adult cells, MET is present in low to normal levels to support natural cellular function, but in some cancer cells, MET is continuously activated. When abnormally activated, MET plays multiple roles in human cancer, including cancer cell growth, survival, angiogenesis, invasion, and metastasis.

The drug’s developers plan to hold discussions with cancer experts to determine how to proceed with the clinical development of tivantinib.

Sources: ArQule, Inc.; January 11, 2013; and Reuters; January 11, 2013.

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