• 4/5/2006
  • Woburn, MA
  • press release
  • Pharmalive.com

ArQule, Inc. today reported results from a Phase 1 monotherapy trial with its lead product, ARQ 501, which provided evidence of clinical tolerability and promising anti-tumor activity in cancer patients with advanced solid tumors who had failed prior treatments with chemotherapy.

Data from this trial were presented by the study’s principal investigator, Dr. Geoffrey I. Shapiro of the Dana-Farber Cancer Institute / Harvard Medical School, and Dr. Chiang J. Li, senior vice president and chief scientific officer of ArQule, in the late-breaking poster session at the 97th Annual Meeting of the American Association for Cancer Research (AACR) in Washington, D.C.

“The exciting data presented today, combined with the potent and selective anti-cancer activity of ARQ 501 seen in a broad range of pre-clinical models, provide a strong rationale for initiating a Phase 2 clinical development program,” said Dr. Stephen A. Hill, president and chief executive officer of ArQule. “These encouraging data also begin to define the clinical profile related to ARQ 501’s novel mechanism of action.”

“ARQ 501 is being developed to selectively and broadly target cancer cells by directly activating checkpoint pathways,” said Dr. Li. “We are excited by what we have seen with this novel mechanism of action. Among the patients who are evaluable for efficacy, almost half showed evidence of tumor regression or stable disease. This is particularly encouraging given that the data are from a Phase 1 dose escalation trial among patients who have failed other therapies.”

Study summary

Subjects in this trial received either one or three-hour infusions of ARQ 501 as monotherapy. Infusions were repeated weekly, every other week or two out of three weeks. Dose escalation was conducted to explore and evaluate the effects of both doses and infusion regimens. Tumor response was evaluated according to RECIST (Response Evaluation Criteria in Solid Tumors) criteria.

ARQ 501 was administered to 64 patients with late-stage cancer who had received prior regimens of chemotherapy. Doses ranged from 10 milligrams per meter squared (mg/m(2)) to 660 mg/m(2). Tumor regression or prolonged disease stabilization was observed in a broad spectrum of cancer types, including pancreatic cancer, head and neck cancer, ovarian cancer, colorectal cancer and leiomyosarcoma.

Evidence of anti-tumor activity was observed in 18 out of 38 patients evaluable for efficacy. Of these 18 patients, evidence of tumor regression was observed in five patients, two of whom had partial responses and three of whom had minor responses (tumor regression by more than 15% but less than 30% per RECIST). In addition, 13 of these patients achieved disease stabilization.

The data also demonstrated the clinical tolerability and favorable pharmacokinetics of ARQ 501. Drug-related serious adverse events included hemolytic anemia and hyperbilirubinemia, although these were transient and clinically manageable. Hemolytic anemia was identified as the dose-limiting toxicity associated with administration of ARQ 501.

About ARQ 501

ARQ 501, the Company’s lead product generated from its Activated Checkpoint Therapy(SM) (ACT) platform, is being developed under an alliance with Roche. ACT compounds are designed to selectively and broadly target cancer cells through activation of checkpoint pathways. ARQ 501 activates E2F1-mediated checkpoint pathways, resulting in apoptosis (cell suicide) in cancer cells selectively.

Based on data from Phase 1 trials, the Phase 2 development plan for ARQ 501 has been established and will include monotherapy trials in leiomyosarcoma and head and neck cancer, as well as combination therapy trials with gemcitabine in pancreatic cancer and with paclitaxel in ovarian cancer.

About ArQule

ArQule, Inc. is a biotechnology company engaged in the research and development of next-generation, small-molecule cancer therapeutics. The Company’s targeted, broad-spectrum products are designed to affect key biological processes that are central to cancer. ArQule’s innovative Activated Checkpoint Therapy(SM) (ACT) platform is generating products designed to improve the way cancer patients are treated by selectively killing cancer cells and sparing normal cells through direct activation of DNA damage response/checkpoint pathways.