Telik Inc., made its presence felt at a tri-sponsored cancer meeting in Germany, presenting data from a preclinical trial of TLK286 given in combination with chemotherapeutic drugs, and three Phase II trials of the drug in various cancers.
The Symposium on Molecular Targets and Cancer Therapeutics - sponsored by the European Organization for Research and Treatment of Cancer, National Cancer Institute and American Association for Cancer Research - was held in Frankfurt, Germany.
TLK286, a small-molecule antitumor drug, is activated by GST P1-1, an enzyme found in higher levels in some human cancers than in normal tissue. The product is designed to initiate apoptosis.
The preclinical studies evaluated TLK286 in combination with chemotherapeutic drugs. In a study of TLK286 alone and in combination with doxorubicin or carboplatin on a human ovarian cancer cell line, an enhancement of cytotoxicity was seen when the product was combined with the anticancer agents. TLK286 also was tested in combination with docetaxel in a human breast cancer cell line, a study in which the combination was shown to be more effective at inhibiting cell proliferation than either of the drugs alone. In a human colon cancer cell line, TLK286 in combination with oxaliplatin was more effective in inhibiting cancer cell growth than either drug alone.
The TLK286 Phase II refractory colorectal cancer trial involved 73 patients who had failed 5-fluorouracil, leucovorin and irinotecan chemotherapy. Sixty-eight percent also had failed additional salvage therapy. TLK286 treatment resulted in a median time to tumor progression of 2.9 months, an increase over both oxaliplatin (1.6 months) and 5-FU/LV (2.7 months). The drug also showed an improvement in median survival time.
The TLK286 Phase II platinum-refractory or resistant ovarian cancer trial in 36 patients had not reached median survival yet at the time of presentation, but median survival exceeds 16 months. Sixty-three percent of patients are still alive, Telik said.
The Phase II trial of TLK286 in 51 platinum refractory or resistant non-small-cell lung cancer patients showed the product prolonged expected survival and had significant single-agent activity in patients with highly resistant disease. Overall, median survival in the trial was nine months, with 38 percent of patients alive at one year.
Telik's stock (NASDAQ:TELK) fell 46 cents Wednesday to close at $12.78.
In other news from the symposium:
• Onyx Pharmaceuticals Inc., of Richmond, Calif., reported Phase I data for BAY 43-9006, an orally active small molecule of raf kinase inhibitor being developed in collaboration with Bayer AG, of Leverkusen, Germany. Data presented showed that twenty-seven of 114 patients treated at higher doses remain on BAY 43-9006 with disease that had not progressed after more than six months, and seven patients have been treated with BAY 43-9006 for more than one year, also with no disease progression. Of those, a patient with a previously reported partial response with hepatocellular carcinoma has remained on BAY 43-9006 therapy without progression for more than nine months, and a second patient with a partial response with renal cell carcinoma was in the study for 44 weeks before progressing.
• Kosan Biosciences Inc., of Hayward, Calif., and F. Hoffmann-La Roche Ltd., of Basel, Switzerland, reported interim results from a Phase I trial of KOS-862 (Epothilone D). To date, the drug has been administered to 42 patients with results indicating no apparent myelosuppression. KOS-862 is a polyketide natural product designed to inhibit cancer cells.
• FeRx Inc., of San Diego, reported data from a Phase I/II trial of hepatic intra-arterial delivery of doxorubicin hydrochloride absorbed to magnetic targeted carriers in patients with hepatocellular carcinoma. Response data showed that in 21 lesions on 19 patients treated at doses greater than or equal to 0.4 mg of doxorubicin/cm2 of tumor area, there was one complete response, two partial responses, seven minor responses, seven patients with stable disease and four patients with progressive disease. The median survival time was 11 months.
• Vion Pharmaceuticals Inc., of New Haven, Conn., reported preclinical data on its product, Triapine, showing that it increases uptake of gemcitabine in cancer cells and increases the incorporation of gemcitabine into cellular DNA. Combining nontoxic doses of Triapine, followed by short exposure to gemcitabine produced synergistic anticancer activity in vitro, the company said. Vion anticipates initiating Phase II trials of Triapine in combination with gemcitabine in the first half of 2003. Separately, the company said it reported data from VNP40101M in solid tumors in 23 patients with advanced cancer of different origins that was considered unresponsive to or had progressed after standard treatments. VNP40101M was well tolerated across all dose levels and the highest dose tested was associated with reversible moderate reduction of platelet counts.
• NewBiotics Inc., of San Diego, presented preliminary data from its first Phase I trial of Thymectacin (NB1011) in drug-resistant colon cancer, showing the drug was well tolerated at all dose levels tested. Twenty-four patients with advanced colorectal cancer who failed standard chemotherapy treatment received Thymectacin in escalating doses. Also, four patients in the trial have exhibited stable disease.