Akt InhibitorClinical Trial
VioQuest Pharmaceuticals announced that it will proceed with Phase II trials later this year with its direct Akt inhibitor VQD-002.
Ongoing trials in patients with refractory leukemia and solid tumors are expected to complete phase I enrollment in June 2007. VQD-002 is a novel direct inhibitor of activation of Akt, a serine-threonine kinase that is over expressed and or hyperactivated in resistant and refractory tumors as well as in aggressive hematologic malignancies. Phase I/IIa clinical trials are currently ongoing at the MD Anderson Cancer Center, Houston, TX, and at the H. Lee Moffitt Cancer Center, Tampa, FL.
The objectives of the clinical trials in hematologic malignancies conducted at MD Anderson and H. Lee Moffitt Cancer Center, include the evaluation of VQD-002's safety profile, pharmacokinetic (PK) and pharmacodynamic (PD) parameters, and the effects VQD-002 has on Akt modulation. Eleven patients have been enrolled in the ongoing leukemia trial. In the leukemia trial, reductions in malignant cells (peripheral blast cells) have been seen in several of the patients following initial therapy. Some patients have had improvements observed in parameters of their bone marrow function (increases in platelet and neutraphil counts).
The objectives of the clinical trial in solid tumors conducted at H. Lee Moffitt Cancer Center, include the evaluation of VQD-002's safety profile, pharmacokinetic (PK) and pharmacodynamic (PD) parameters, and the effects VQD- 002 has on Akt modulation. Eleven patients with solid tumors have been enrolled in the phase I portion of the ongoing solid tumor trial. Several of these patients, refractory to prior standard therapy and who were screened and selected for study based on the high level of Akt expression in their tumors, have shown stable disease on study.
Phase I enrollment in both the solid tumor and leukemia trials is expected to be completed in June 2007, with phase IIa expansion in each trial starting immediately thereafter in patients with a variety of resistant/refractory solid tumors and malignant leukemias. Akt screening before and during patient treatment will continue to be performed on these patients.
"As the pathophysiology of hematologic malignancies continues to be dissected, Akt is emerging as an important therapeutic target for both single therapeutic agent modulation and the development of combinatorial molecular targeted therapeutics," said Professor Frank Giles, Director of the Institute for Drug Development, CTRC and Chairman of the Division of Hematology and Medical Oncology at the University of Texas Health Science Center, San Antonio. "VQD-002 is an exciting novel agent in the context of personalized medicine and molecular targeted therapeutics, coupled with activities seen in the ongoing trials so far, we are enthusiastic about investigating rapidly," said Professor Giles, who is Chairman of the VioQuest Scientific Advisory Board.
"It is important to note that our Akt activation inhibitor not only blocks the function of all three isoforms of Akt, but also does not result in feedback upregulation of P-Akt levels as observed in other Akt inhibitors. This is a selective, specific, and potent inhibitor of Akt activation. Accordingly, VioQuest would like to exploit this advantage in future combination studies," explained Said M. Sebti, Ph.D., M.D., Director of Drug Discovery Program, Moffitt Cancer Center, Tampa, FL.
"While these phase I data should not be overinterpreted, the fact that VQD-002 is being well-tolerated in this advanced patient population is encouraging and supports the substantial and growing pre-clinical data which points to Akt as a key cancer control pathway," said Edward C. Bradley, M.D., VioQuest's Chief Scientific Officer.
Discussions of additional Phase II trials of VQD-002 used in combination with other targeted therapies are underway and patient enrollment in these trials could begin by the end of this year.