Tivantinib Study Halted Following Interim Analysis

The phase III MARQUEE trial examining tivantinib has been halted following a planned interim analysis because it was not expected to meet its primary endpoint, ArQule Inc. and Daiichi Sankyo Co. announced on October 2.

The randomized, double-blind MARQUEE study evaluated erlotinib plus the oral MET inhibitor tivantinib (ARQ 197) versus erlotinib plus placebo in previously treated patients with locally advanced or metastatic, non-squamous, non-small cell lung cancer (NSCLC). Tivantinib binds to the MET receptor tyrosine kinase and blocks the MET signaling pathway. The result is a disruption in the signals that cause tumor cell proliferation and metastasis.

The study’s independent data monitoring committee determined that the primary endpoint of improvement in overall survival (OS) would not be met. The independent group did find improvement in progression-free survival (PFS) in the intent-to-treat (ITT) group and found no safety concerns.

"We are disappointed that the MARQUEE trial did not provide statistically significant results for overall survival in a disease and treatment setting which remains a major unmet medical need," ArQule Chief Executive Officer Paolo Pucci said.

MARQUEE was conducted in more than 200 clinical sites worldwide. Secondary endpoints of the study included OS in the subpopulation of patients with epidermal growth factor receptor wild type, PFS in the ITT group, and further evaluation of tivantinib’s safety in combination with erlotinib.

The phase II trial that was the foundation for the MARQUEE trial indicated that the combination of tivantinib and erlotinib improved median OS versus erlotinib alone in patients with non-squamous NSCLC by 46% (10.1 vs 6.9 months, P = .18). The trial also showed a 91% improvement in average PFS (4.4 vs 2.3 months, P = .12).

In the phase I and II studies of the combination, patients tolerated tivantinib and saw minimal increases in side effects beyond those with erlotinib alone.

Tivantinib continues to be studied as a monotherapy and as a part of combinations to treat many cancers including NSCLC, hepatocellular carcinoma, colorectal cancer, and gastric cancer.

"Fighting cancer is a complex process in that therapies work differently in different tumor settings, so we will continue to investigate tivantinib in other tumor types," said Glenn Gormley, MD, PhD, global head, R&D and senior executive officer, Daiichi Sankyo Co., Ltd.

In 2008, ArQule and Daiichi Sankyo agreed to co-develop and commercialize tivantinib in the United States, Europe, South America, and the rest of the world, excluding Japan, China (including Hong Kong), South Korea and Taiwan.