Study Presented at ASCO Shows Encouraging Preliminary Results for Phase II
- Category: DNA RNA and Cells
- Published on Sunday, 03 June 2007 04:00
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VANCOUVER, Canada and CARLSBAD, CA, USA | June 2, 2007 | OncoGenex Technologies Inc. and Isis Pharmaceuticals, Inc. (Nasdaq: ISIS) today announced preliminary data from a Phase II clinical trial of OGX-011 in combination withdocetaxel and prednisone in patients with metastatic hormone refractory prostate cancer(HRPC). Data were presented by Dr. Kim Chi, Study Chair and a medical oncologist atBC Cancer Agency – Vancouver Centre, representing the National Cancer Institute ofCanada – Clinical Trials Group at the Annual Meeting of the American Society of ClinicalOncology (ASCO) in Chicago.
Eighty-one patients with metastatic or locally recurrent prostate cancer refractory tohormone therapy were randomized to one of two treatment arms to receive either 640mg OGX-011 per week in combination with docetaxel and prednisone or docetaxel andprednisone alone. As of May 14, 2007 all 81 patients had been followed for a minimumof 4.8 months. Currently, 22 percent of patients are still receiving study treatment and allpatients continue to be followed.
Summary of Preliminary Results from this Ongoing Study:
--The median duration of progression-free survival was 7.3 months in patients who received OGX-011 plus docetaxel and 5.8 months in patients who receiveddocetaxel.
-- Disease progression occurred in fewer patients who received OGX-011 plusdocetaxel:
- Progressive measurable disease as the best response occurred in 4 percentof patients in the OGX-011 plus docetaxel arm and in 22 percent of patientsin the docetaxel arm.
- PSA progression as the best response occurred in no patients in the OGX-011 plus docetaxel arm and in 10 percent of patients in the docetaxel arm.
-- While response rates for both measurable disease and PSA assessments in thestudy arms were similar, disease stabilization, by both assessments, occurred inmore patients in the OGX-011 plus docetaxel arm.
- Stable measurable disease as the best response occurred in 73 percent ofpatients in the OGX-011 plus docetaxel arm (median duration 9.7 months)and in 52 percent of patients in the docetaxel arm (median duration 7.6months).
- PSA stabilization (i.e. PSA non-response/non-progression) occurred in 45percent of patients in the OGX-011 plus docetaxel arm and in 32 percent of patients in the docetaxel arm.
-- The primary endpoint of PSA response was seen in 20 of 40 patients who receivedOGX-011 plus docetaxel. This number of responses met the criterion for declaringthis combination of interest to explore further. PSA response was seen in 21 of 40patients who received docetaxel, indicating this arm also met the same criterion.
“These preliminary data support the continued development of OGX-011 in prostatecancer,” said Dr. Chi, medical oncologist at the Vancouver Prostate Center and the BCCancer Agency, and the lead investigator in the study. “Follow-up evaluation of allpatients at the completion of study treatment and at six months post treatment willprovide additional information that will allow us to conduct further assessment of thetherapeutic activity of OGX-011.”
“Data from a previously conducted Phase I study in prostate cancer suggest that OGX-011 can effectively regulate its target, clusterin, a protein expressed by tumor cells andassociated with treatment resistance,” said Scott Cormack, president and CEO ofOncoGenex. “We are encouraged with the preliminary results in patients who receivedOGX-011, particularly the high rates of disease stabilization in both assessments ofmeasurable disease and PSA. These data support our further evaluation of thetherapeutic potential of OGX-011 in prostate cancer.”
Study Design and Safety Results
The study was designed as a non-comparative Phase II study. Any differences observedbetween study arms were not designed to be subject to statistical analyses but instead,were intended to guide future development of OGX-011 and to provide preliminaryguidance regarding activity and tolerability. Patients were randomized to one of twotreatment arms to receive either 640 mg per week of OGX-011 by intravenous infusion incombination with docetaxel and prednisone or docetaxel and prednisone alone.
The median number of cycles of chemotherapy administered was 8 in patients whoreceived OGX-011 plus docetaxel (range 1-10) and 6 in patients who received docetaxel(range 1-10).
The investigators concluded that treatment with OGX-011 was well tolerated. All 81treated patients were evaluable for non-hematological and hematological adverseevents. The following events (all grade 1 or 2) were documented more commonly inpatients given OGX-011 plus prednisone and docetaxel than patients given prednisoneand docetaxel alone: fever (50 percent and 15 percent), rigors/chills (60 percent and 7percent), sweating (25 percent and 12 percent), sensory neuropathy (70 percent and 49percent) and limb edema (38 percent and 27 percent). The majority of patientsexperienced granulocytopenia and neutropenia, with similar frequency and magnitude ineach arm. Grade 3/4 lymphopenia was more common in patients receiving OGX-011plus docetaxel (53 percent) than in patients who received docetaxel (20 percent). Ingeneral, the toxicities were consistent for the adverse event profile for docetaxel andprednisone. There were 11 serious adverse events (SAEs) reported for each study arm.
The study was supported by a grant from the Canadian Cancer Society through theNational Cancer Institute of Canada and coordinated by the National Cancer Institute ofCanada Clinical Trials Group (NCIC CTG) based at Queen's University in Kingston,Ontario, which is also funded by the Canadian Cancer Society. The study was furthersupported by OncoGenex, Isis and an unrestricted grant from sanofi-aventis.
OGX-011 is designed to specifically inhibit the production of the cell-survival protein,clusterin. Clusterin production is associated with treatment resistance in many cancersand in response to various cancer treatments, including hormone ablation therapy,chemotherapy and radiation therapy. Preclinical studies have shown that inhibition ofclusterin can disable the tumor cell’s adaptive defences, render the tumor cellssusceptible to attack with a variety of cancer therapies, including chemotherapy, andfacilitate tumor-cell death. OncoGenex and Isis are collaborating on development ofOGX-011, which is the subject of five ongoing Phase II studies evaluating the safety andactivity of OGX-011 in patients with prostate cancer, non-small cell lung cancer andbreast cancer.
OncoGenex is committed to the development and commercialization of new cancertherapies that address treatment resistance in cancer patients. OncoGenex currently hasthree product candidates in development: OGX-011, OGX-427 and OGX-225. Theseproduct candidates are designed to selectively inhibit the production of proteins that areassociated with treatment resistance and that are over-produced in response to a varietyof cancer treatments. OncoGenex’ aim in targeting these particular proteins is to disablethe tumor cells’ adaptive defenses, render the tumor cells susceptible to attack with avariety of cancer therapies including chemotherapy, and facilitate tumor cell death. Moreinformation on OncoGenex and the company’s pipeline is available atwww.oncogenex.ca.
About Isis Pharmaceuticals, Inc.
Isis is exploiting its expertise in RNA to discover and develop novel drugs for its productpipeline and for its partners. The Company has successfully commercialized the world'sfirst antisense drug and has 17 drugs in development. Isis’ drug development programsare focused on treating cardiovascular and metabolic diseases. Isis’ partners aredeveloping drugs for cancer, and inflammatory and other diseases. Ibis Biosciences,Inc., Isis’ wholly owned subsidiary, is developing and commercializing the Ibis T5000Biosensor System, a revolutionary system to identify infectious organisms. As aninnovator in RNA-based drug discovery and development, Isis is the owner or exclusivelicensee of over 1,500 issued patents worldwide. Additional information about Isis isavailable at www.isispharm.com.
SOURCE: OncoGenex Technologies Inc.