Telik, Inc., a biopharmaceutical company working to discover, develop and commercialize small molecule drugs to treat serious diseases for which there is significant demand for new therapies, has presented final results from the Phase 1 dose-escalation trial of its TLK286 product candidate administered using a weekly dosing schedule. TLK286 was well-tolerated in this trial and showed additional evidence of clinical benefit in several cancer types. The results were presented at the 38th annual meeting of the American Society of Clinical Oncology in Orlando, Florida.
TLK286 is a small molecule antitumor drug that has a novel "smart" mechanism of action. TLK286 is activated by GST P1-1, an enzyme that is present in higher levels in many human cancers than in corresponding normal tissues. Elevated levels of GST P1-1 also correlate with chemotherapeutic drug resistance. Upon activation, TLK286 initiates an intracellular process known as apoptosis, or programmed cell death.
"Most chemotherapeutic drugs cause toxicities from which patients must recover before receiving subsequent doses," said Michael M. Wick, M.D., Ph.D., chairman and CEO. "Toxicities can also accumulate and cause damage to organ systems that precludes patients from continuing treatment.
"In this and other trials, TLK286 administration has been associated with generally mild toxicities, most of which has been classified as Grade 1 or 2 in severity. There have been few Grade 3 and no Grade 4 adverse events. Further, TLK286 has been administered on both weekly and every three week schedules for extended periods (more than 17 months on the weekly schedule, and 10 months on an every three week dose schedule) without evidence of cumulative toxicity," Dr. Wick said.
In this Phase 1 trial, 37 patients were treated with escalating doses of TLK286. Indications of anti-tumor activity were observed in several advanced malignancies including colorectal, renal, lung and thyroid cancers and sarcomas.
Telik also has conducted a multicenter Phase 2 clinical trial in patients with advanced metastatic colorectal cancer. A total of 73 patients were enrolled in the trial. Of the 36 patients evaluable for efficacy at the time of analysis, disease stabilization has been observed as well as decreases in serum CEA tumor marker. Due to the small proportion of patients evaluable for efficacy, it is not currently possible to determine the median time to tumor progression or survival. TLK286 has been generally well-tolerated in this trial, with adverse events similar in type and severity as has been observed in other clinical trials of TLK286.