Lorus Therapeutics Inc., a biopharmaceutical company specializing in the research and development of pharmaceutical products and technologies for the management of cancer, announced completion of a proof of concept clinical trial in Acute Myeloid Leukaemia (AML), and expansion of its GTI-2040 development programme in this indication, with initiation of a more advanced phase II clinical trial with GTI-2040 and high dose Ara-C (HiDAC) in refractory and relapsed AML.
The advanced phase II clinical trial, which is now underway includes both an efficacy study and a novel additional study to measure intracellular target activities and pharmacological synergies between the two agents. In the first stage of the 60 patient trial, the pharmacologic and target related activity of GTI-2040 and HiDAC will be evaluated in two groups, to determine the contribution of each agent alone and in combination. The second stage of the trial will provide efficacy evaluation in a larger patient population. Lorus expects the clinical trial to be completed by the end of 2008.
The decision by Lorus to advance clinical development of GTI-2040 is based on the encouraging results from our recently completed proof of concept study of GTI-2040 in combination with HiDAC in patients with refractory and relapsed AML. This clinical trial demonstrated safety and appropriate dosing of the combination regimen and showed promising clinical responses in patients under 60 years of age. Moreover, the clinical responses correlated with down regulation of R2, the cellular target of GTI-2040, and were further supported by demonstration of intracellular TI-2040 in circulating and bone marrow leukemic cells. Complete results from the clinical trial are expected to be presented by the investigators in a scientific publication.
"The initiation of an advanced Phase II clinical trial with GTI-2040 is a very significant step forward for Lorus, and for the development of its clinical stage pipeline. This underscores the dedication of Lorus' clinical and regulatory teams to the development of novel anticancer agents", commented Dr. Aiping Young, president & CEO of Lorus. "The clinical data for GTI-2040 in AML are consistent with an antisense mode of action, and the frequency of responses and statistical correlation of this with target activity are very encouraging. We believe that this drug will provide an important new treatment opportunity for AML patients."
This new advanced Phase II clinical trial is sponsored by Lorus and is being led by Dr. Rebecca Klisovic as Principal Investigator and Dr. Guido Marcucci as coinvestigator, at The Comprehensive Cancer Center of Ohio State University. Dr. Marcucci was also the Principal Investigator on the previous clinical trial of GTI-2040 in AML, which was carried out with the sponsorship of the Cancer Therapy Evaluation Program of the US National Cancer Institute. Dr. Marcucci and his team at OSU have extensive experience with antisense and other targeted therapies in leukaemic indications and in genetic studies of leukaemia.
Ara-C, including HiDAC, is a key component of nearly all AML regimens, for induction, consolidation or salvage treatment. However even with intensification of the Ara-C, response to treatment in refractory and relapsed disease is limited by development of increasing resistance to Ara-C with repeated exposures. Combining GTI-2040 with Ara-C is a rational approach that in addition to potential cooperative activities may overcome resistance to Ara-C.
GTI-2040 is an antisense drug that specifically targets the R2 component of ribonucleotide reductase, which is required for DNA synthesis and cell proliferation. Through down regulation of R2, GTI-2040 has demonstrated strong anti-tumour and antimetastatic activity in a variety of tumour types in both in vivo and in vitro models and is under study in a multiple Phase I/II clinical program. R2 has been described as a malignant determinant that is elevated in a wide range of tumours, which can cooperate with a variety of cellular cancer causing genes known as oncogenes to enhance tumour growth and metastatic potential.