By Debbie Strickland
Special To BioWorld Today
ATLANTA ¿ New clinical data suggest that Biomira Inc.¿s Theratope cancer vaccine can improve survival and lessen the risk of relapse in ovarian and breast cancer patients who undergo high-dose chemotherapy and autologous stem cell transplantation.
The data were presented at the American Society of Clinical Oncology meeting here, and were a bright spot in an otherwise cloudy picture for that treatment regimen. While results were mixed, and some were preliminary, data from several large Phase III studies presented at ASCO showed no survival gains for breast cancer patients undergoing the basic procedure.
¿One of the concerns circulating is that maybe high-dose chemotherapy is not the wonderful treatment we thought it would be,¿ said Grant MacLean, Biomira¿s vice president for clinical and regulatory affairs. ¿Chemotherapy on its own is not the complete answer for women with metastatic breast cancer [the lead indication for Theratope].¿
A more effective therapy, he said, may be one that combines ¿the best available chemotherapy and the best available immunotherapy.¿
In the Theratope study ¿ a Phase II physician-sponsored trial ¿ researchers at the Fred Hutchinson Cancer Research Center in Seattle treated 40 cancer patients (11 high-risk stage II/III breast, 22 stage IV breast, and 7 stage III/IV ovarian) with high-dose chemotherapy followed by autologous stem-cell transplantation. Twenty-six of the 40 patients also received five doses of Theratope.
Patients in the control group were twice as likely to die than patients vaccinated with Theratope. The chance of relapse was approximately 1.7 times greater for patients in the control group. The company also noted that patients with the highest amount of specific killing activity against STn-bearing cells appeared to remain longest in remission.
Theratope is a synthetic carbohydrate vaccine partnered with Chiron Corp., of Emeryville, Calif. An improved formulation of the product entered a 900-patient Phase III trial at more than 70 sites in December. The trial is unusual in that rather than selecting a single chemotherapeutic regimen, it is open to patients treated with a variety of chemotherapies, including high-dose chemotherapy and bone-marrow transplant, as long as they meet a set of standardized eligibility requirements.
¿This is an approach that appeals to the FDA,¿ said MacLean, because ¿it is based on real-world practice.¿ An added benefit for Biomira is that heterogeneous recruitment will avoid binding the vaccine to a particular chemotherapeutic regimen that later could fall out of favor and leave Theratope stranded.
¿It¿s going to be interesting to see how much high-dose chemotherapy is used,¿ he said, noting that the more generalized breast cancer studies on the procedure released at ASCO produced ¿a lot of long faces.¿
Preliminary results from the largest of those studies ¿ a 783-patient trial conducted at the Cancer and Leukemia Group B ¿ indicate that a patient receiving the high-dose therapy has a 78 percent chance of surviving at least three years, while an intermediate-dose patient has an 80 percent chance.
2,500 Abstracts Sets ASCO Record
Nearly 19,000 cancer specialists from some 70 countries attended the conference, which began Saturday and ended Tuesday.
Nearly 2,500 abstracts were presented and published ¿ a new record, with new studies addressing every area of clinical cancer research, including chemotherapy, radiosurgery, molecular diagnostics, chemoprevention, gene therapy and cancer vaccines.
For those unable to attend, ¿virtual meeting¿ access is available at www.asco.org.
In other news from the conference:
¿ AnorMED Inc., of Vancouver, British Columbia, said preliminary Phase I data showed its platinum-based drug, ZD0473, has a favorable toxicity profile and warrants further development.
¿ Antigenics LLC, of New York, said a 42-patient Phase I/II trial of HSPPC-96, an autologous protein, showed no vaccine-related adverse events and a preliminary suggestion of clinical activity. The company has begun an accelerated Phase II trial in renal cell carcinoma.
¿ Cell Genesys Inc., of Foster City, Calif., said new findings from a Phase I/II trial of GVAX prostate cancer vaccine strongly confirmed the induction of a specific antitumor immunity. Fourteen of the 15 patients (out of 21) who achieved disease stabilization produced specific antibodies directed against prostate cancer cells. None of the six patients with progressive disease produced those antibodies.
¿ Cell Pathways Inc., of Horsham, Pa., said cell culture and animal model results showed synergy between its drug, exisulind, and conventional cancer drugs. It also noted publication of results showing exisulind¿s ability to induce apoptosis in leukemia and myeloma cell lines.
¿ Isis Pharmaceuticals, of Carlsbad, Calif., presented data showing three antisense drug candidates were well tolerated. The data came from Phase I trials of ISIS 3521, ISIS 5132 and ISIS 2503. Results from early trials of the drugs in combination with standard chemotherapeutics showed partial responses and disease stabilization in some patients.
¿ Protein Design Labs Inc., of Fremont, Calif., said a Phase I study of its Smart Anti-CD3 Antibody in 15 patients with end-stage renal disease who were scheduled to undergo liver transplantation showed depletion of T lymphocytes at the three highest doses. A Phase I/II trial is ongoing.
¿ Sugen Inc., of South San Francisco, said final Phase I data from a study of SU5416 showed the angiogenesis inhibitor was well tolerated for chronic administration at biologically active doses. There also was demonstration of activity against certain tumor types and disease stabilization in many patients.
¿ Titan Pharmaceuticals Inc., of South San Francisco, said an ongoing Phase II study of TriGem showed 40 of 47 patients generated strong anticancer immune responses to the therapeutic monoclonal antibody vaccine, with one patient achieving a complete response and 17 patients with stable disease for periods ranging from 10 to 36 months. In a Phase II trial of the vaccine TriAb, a strong immune response against the breast cancer antigen HMFG was demonstrated in 20 of 21 patients.
¿ Vertex Pharmaceuticals Inc., of Cambridge, Mass., said results from a Phase II trial of Incel, in combination with doxorubicin, suggested it helped restore tumor sensitivity to chemotherapy in some patients who had failed prior doxorubicin treatment. In a set of 15 evaluable patients with soft-tissue sarcoma, 60 percent demonstrated overall clinical benefit.
¿ Xenova Group plc, of Slough, U.K., said Phase I results of intravenous and oral delivery of its P-glycoprotein inhibitor, XR9576, demonstrated it was well tolerated at all doses and gave complete inhibition of P-gp. Phase II trials are under way.