ArQule, Inc. and Daiichi Sankyo, Co., Ltd. (TSE 4568) today announced that an oral presentation at the Annual Meeting of the American Society of Clinical Oncology (ASCO) will feature Phase 2 trial data with tivantinib as a single agent investigational second-line treatment in hepatocellular carcinoma (HCC). ArQule announced that this randomized, double-blind study met its primary endpoint in January and will now present the full results from this trial, including positive data in the pre-defined c-MET high population.

Additional clinical data with tivantinib will be featured in two poster discussions and two general poster sessions. 

"These findings represent the first randomized data reported with an investigational c-MET inhibitor administered as a single agent second-line treatment in HCC," said Paolo Pucci, chief executive officer of ArQule. "They clearly define c-MET high patients as a biological subgroup for potential targeted therapy with tivantinib. The robust statistical significance achieved in this trial reflects the anti-cancer activity of tivantinib alone and expands its therapeutic potential."

HCC Trial Summary: c-MET high patients

Data from the HCC trial demonstrated a statistically significant improvement in time-to-progression (HR=0.43, log rank p-value=0.03), accompanied by significant improvements in progression-free survival and disease control rate among second-line patients with c-MET high tumors who were treated with tivantinib. In addition, overall survival data were observed favoring tivantinib-treated patients in this population. Efficacy was similar in the two tivantinib dosing subgroups (360 milligrams twice daily and 240 milligrams twice daily), with less frequent neutropenia in the lower dose.

Previously announced top-line data from the HCC trial demonstrate that treatment with tivantinib produced a statistically significant 56 percent improvement in TTP in the intent-to-treat (ITT) population by central radiology review, the primary endpoint (HR = 0.64, log rank p-value = 0.04) in this trial. Adverse events were reported at similar rates in the treatment and placebo arms, except for a higher incidence of fatigue and hematologic events, including neutropenia and anemia, in tivantinib-treated patients. The incidence of hematologic events declined following dose reduction of tivantinib from 360 milligrams twice daily to 240 milligrams twice daily.

The schedule of this and other presentations of data with tivantinib is provided below. All times are Central Daylight Time.

Oral Presentation Date and time: Saturday, June 2, 2012, 5:00 PM - 5:15 PM Abstract number: 4005 Poster title: Tivantinib (ARQ 197) versus placebo in patients (Pts) with hepatocellular carcinoma (HCC) who failed one systemic therapy: Results of a randomized controlled phase II trial (RCT) Presenter: Lorenza Rimassa, MD Location: E Hall D1 Poster Discussion Sessions Date and time: Saturday, June 2, 2012, 8:00 AM - 12:00 PM Abstract number: 4545 Poster title: Safety and efficacy of MET inhibitor tivantinib (ARQ 197) combined with sorafenib in patients (pts) with renal cell carcinoma (RCC) from a phase 1 study Poster board # 24 Presenter: Igor Puzanov, MD Location: E450a Date and time: Saturday, June 2, 2012, 1:15 PM - 5:15 PM Abstract number: 8519 Poster title: Safety and efficacy of MET inhibitor tivantinib (ARQ 197) combined with sorafenib in patients (pts) with NRAS wild-type or mutant melanoma from a phase 1 study Poster board # 8 Presenter: Julie A. Means-Powell, MD Location: E450b General Poster Session Date and time: Monday, June 4, 2012, 8:00 AM - 12:00 PM Abstract number: 4117 Poster title: Safety and efficacy of MET inhibitor tivantinib (ARQ 197) combined with sorafenib in patients (pts) with hepatocellular carcinoma (HCC) from a phase 1 study Poster board # 50D Presenter: Robert E. Martell, MD, PhD Location: S Hall A2 Date and time: Monday, June 4, 2012, 8:00 AM - 12:00 PM Abstract number: 4082 Poster title: A phase II study of tivantinib monotherapy in patients with previously treated advanced or recurrent gastric cancer Poster board # 46A Presenter: Kei Muro, MD Location: S Hall A2

Tivantinib is currently in Phase 3 development and has not yet been approved for any indication.