Arqule's ACT platform is intended to improve the way cancer patients are treated as they selectively kill cancer cells and spare normal cells by restoring and activating cellular checkpoints that are defective in cancer. The result should be improved efficacy and reduced toxicity. Further, compounds resulting from the ACT platform are designed to apply to a broad spectrum of cancers and counteract cancer heterogeneity.
The interim results for the ongoing phase 1 trial of ARQ 501 were presented at the annual meeting of the American Society of Clinical Oncology (ASCO). The ASCO conference, which took place in Orlando, Florida between May 13-17 took the opportunity to present the best of clinical and translational cancer research.
The interim results demonstrate clinical tolerability, favourable pharmacokinetics, and evidence of anti-tumour activity of ARQ 501 in patients with advanced solid tumours who had failed chemotherapy. Out of 16 patients who are evaluable for efficacy, 62.5 per cent showed either tumour regression (1 partial response, 2 minor responses) or disease stabilisation (7 patients).
As of March 24, 2005, the study enrolled a total of 32 patients who had failed prior regimens of chemotherapy, ranging from 1 to 15 courses per patient. Of the 26 patients who were evaluable for pharmacokinetic analysis, 20 patients had received ARQ 501 as a 1-hour infusion and 6 patients had received ARQ 501 on different infusion regimens.
Adverse events have been mild or self-limited. Haemolytic anaemia and hyperbilirubinemia were noted as drug-related serious adverse events, which were transient and clinically manageable.
The ARQ 501 monotherapy trial continues to enroll patients in dosing ranges of between 390 and 550 mg/m2, with infusion times between 1 and 3 hours. Once the optimal infusion time is identified, the maximal tolerated dose will be determined through dose escalation.
"Our goal is to reduce the overall risk and time involved in clinical development, rather than rushing into determining a maximum tolerated dose, as might be done for chemotherapeutic agents," said Dr Chiang Li, ArQule's chief scientific officer.
We would like to complete Phase 1 with an optimised dosing regimen and biomarkers for patient selection in our intended phase 2 studies," he added.
ARQ 501 is considered to be ArQule's strongest product within its pipeline and originated as a result of the 2002's acquisition of Cyclis Pharmaceuticals.
"Cyclis researchers conducted a research programme and came up with a natural compound - Betalapachone. It was originally found in South American trees but we do have a synthetic route for it," said Dr Stephen Hill, ArQule's President and Chief Executive Officer.