Telik Inc. reported data from a trio of Phase I/IIa studies of Telcyta (TLK286) at the International Conference on Molecular Targets and Cancer Therapeutics in Boston, jointly sponsored by the American Association for Cancer Research, the National Cancer Institute and the European Organization for Research and Treatment of Cancer.
Among the findings, the Palo Alto, Calif.-based company said one study showed that Telcyta combined with carboplatin demonstrated a 63 percent objective response rate and an 88 percent overall disease-stabilization rate in advanced patients with resistant ovarian cancer. Telcyta combined with Doxil in the same indication resulted in a 33 percent objective response rate and a 100 percent disease-stabilization rate. A Telcyta combination with docetaxel in resistant non-small-cell lung cancer patients resulted in a 29 percent objective response rate and a 69 percent disease-stabilization rate.
All combinations were well tolerated.
Separately, the company presented results from a Phase I/IIa study of Telintra (TLK199) in 16 myelodysplastic syndrome patients that showed 56 percent had clinically significant improvement in at least one of the three blood cell lineages (red cells, white cells, platelets). Nineteen percent had reduced requirements for blood support, and 31 percent had an objective response as defined as hematologic improvement.
In other news from the conference:
• Cell Therapeutics Inc., of Seattle, said preliminary Phase I data showed that treatment with its polyglutamate camptothecin, CT-2106, produced generally mild to moderate side effects. Dose-limiting toxicity events in the 19-patient study included neutropenia (one patient with Grade 4) and thromobocytopenia (three patients with Grade 3). There were no reports of severe bladder toxicity, a side effect of 20S-camptothecin.
• The Centre for Developmental Cancer Therapeutics in Melbourne, Australia, said preliminary Phase II results showed that treatment with a compound called SU11248 resulted in a major response for two patients out of 41, as assessed by the degree of tumor shrinkage. A further 15 patients had benefit defined as no progression of their cancer and continued therapy beyond the 12-week study. Most had improved symptoms or reduced tumor activity, while some also had significant tumor shrinkage that was less than that required to meet the criteria for major response.
• Cyclacel Ltd., of Dundee, UK, said interim Phase I results showed that treatment with its small-molecule CDK inhibitor, CYC202, resulted in stable disease or tumor regression in several patients with advanced tumors who had previously failed several lines of chemotherapy. Separate preclinical data on the use of CYC202 with docetaxel showed that the combination exhibited marked synergy over either treatment alone.
• EntreMed Inc., of Rockville, Md., said preclinical results demonstrated that its new formulations of Panzem have increased antitumor activity that leads to greater inhibition of tumor growth when compared to the same doses of the current clinical formulation. The increase in tumor inhibition was associated with significant improvement in the new formulations' bioavailability, leading to higher blood levels of Panzem after oral dosing in preclinical models. EntreMed's lead drug candidate is in Phase I and II oncology trials, and additional clinical trials with a newly formulated version are scheduled to begin during the first half of next year.
• Geron Corp., of Menlo Park, Calif., reported preclinical data showing that its lipidated telomerase inhibitor cancer drug candidate, GRN163L, demonstrated enhanced bioavailability and potency, while maintaining high specificity to telomerase; good safety and tolerability; and appropriate stability in both liquid and freeze-dried formulations. More specifically, treatment with GRN163L induces apoptosis in cancer cells in vitro, and demonstrates substantial antitumor efficacy in vivo against multiple tumor types following systemic administration at well-tolerated doses.
• Hybridon Inc., of Cambridge, Mass., said preliminary Phase I results showed that HYB2055, its second-generation immunomodulatory oligonucleotide (IMO) that is being developed as IMOxine for oncology applications, resulted in stable disease among five of eight patients at eight weeks. Also, one of three patients evaluated at 16 weeks of treatment had stable disease. A separate placebo-controlled, dose-escalating study in healthy volunteers showed IMOxine to be well tolerated. In preclinical studies, both IMOxine and its mouse analogue, HYB2048, inhibited tumor growth and prolonged survival of mice bearing melanoma or colon carcinoma. A separate study by collaborators at the University of Alabama at Birmingham showed that IMOxine demonstrated tumor growth inhibition in nude mice bearing various human lung, breast, colon, prostate and glioblastoma cancer xenografts.
• ImClone Systems Inc., of New York, updated several preclinical programs. The company reported data suggesting that an investigational fully human monoclonal antibody called 18F1 effectively blocked the binding of vascular endothelial growth factor and placental growth factor, and inhibited tumor cell growth in a xenograft mouse model of VEGFR-1-expressing human breast cancer. Another monoclonal antibody, EB10, blocked binding of the FLT-3 ligand, thereby preventing activation of FLT-3 signaling in acute myeloid leukemia cells and subsequent inhibition of tumor growth. A third antibody, 3G3, inhibited the growth of tumors in xenograft models of glioblastoma and leiomyosarcoma.
• Immunomedics Inc., of Morris Plains, N.J., said preclinical results in a model for human non-Hodgkin's lymphoma showed high efficacy when doxorubicin was attached to IMMU-110, its humanized antibody that targets the CD74 antigen. More specifically, treatment with the candidate was found to cure a large percentage of mice bearing an aggressive form of the disease when given as a single, relatively low dose of the antibody-drug conjugate, even when the animals had advanced disease, while control groups receiving different antibody-drug conjugates showed no improved survival.
• Isis Pharmaceuticals Inc., of Carlsbad, Calif., and Eli Lilly and Co., of Indianapolis, said preclinical results showed that LY2181308, a second-generation antisense drug that targets survivin, inhibited tumor growth. Antitumor activity was associated with significant reduction of survivin expression in tumors, evidence that the drug was working through an antisense mechanism, the partners said.
• Memorial Sloan-Kettering Cancer Center in New York reported Phase I data showing that suberoylanilide hydroxamic acid (SAHA) hit its molecular target (histone deacetylase) in the 60-patient trial, as it did in previous laboratory studies. Investigators also reported a reduction in measurable disease among some patients with solid tumors as well as hematologic malignancies, including one complete remission, following treatment with the oral inhibitor.
• NeoPharm Inc., of Lake Forest, Ill., said preliminary Phase I data indicated that LE-SN38 (liposomal SN38) resulted in stable disease in nine of 27 patients to date, and the compound appears safe and well tolerated at doses up to 20 mg/m2. Dose escalation will continue beyond 20 mg/m2, as planned.
• Onyx Pharmaceuticals Inc., of Richmond, Calif., and Bayer Pharmaceuticals Corp., of West Haven, Conn., said preclinical data on the proposed antitumor activity of BAY 43-9006 indicated that the signal-transduction inhibitor exhibits a dual mechanism of action, targeting both cell proliferation and angiogenesis. Also, an updated data analysis of Phase II results first reported last month showed that of 50 evaluable patients, 42 percent had tumor shrinkage of at least 25 percent at week 12, and 26 percent had their tumors stabilized within 25 percent of pretreatment size. Overall, 68 percent of the cohort did not demonstrate tumor progression by the 12-week evaluation point. The remaining 32 percent discontinued treatment either because of progressive disease or adverse effects.
• Panacea Pharmaceuticals Inc., of Gaithersburg, Md., said that among various findings covering diagnostic and therapeutic applications of its human aspartyl (asparaginyl) beta-hydroxylase (HAAH) oncology program, one report showed that HAAH was detected in the serum of 18 out of 20 pancreatic cancer samples. Also, the use of two monoclonal antibodies detected high-level expression of HAAH in a lung carcinoma cell line, a glioblastoma cell line and a hepatocellular carcinoma cell line.
• Point Therapeutics Inc., of Boston, said preclinical results from a study of PT-100 demonstrated tumor-growth suppression and enhancement of chemotherapy. More specifically, treatment with oral PT-100 inhibited tumor growth when treatment was started seven to eight days after tumor inoculation, and tumor size was reduced by more than 70 percent. When mice were orally treated two days after subcutaneous injection with tumor, before the tumors became established, 50 percent to 70 percent exhibited tumor regression and eventual rejection.
• The University of California at San Francisco presented a new treatment approach using a tumor's own weapon against itself by forcing vascular endothelial growth factor to act as a cell death factor instead of a growth factor. The research team created an artificial VEGF receptor, called R2Fas, and when it was expressed in blood vessel cells, the cells were instead killed by VEGF.