Gene therapy has suffered a few setbacks this past year, most notably the death of a clinical trial patient at the University of Pennsylvania. Nonetheless, many such products continue to move forward, and some, such as Vical Inc.'s Allovectin-7 and Leuvectin anticancer agents, have entered mid- to late-stage trials with regulatory submissions a real possibility. The San Diego company presented interim data on the two "naked DNA" therapies at the 36th annual meeting of the American Society of Clinical Oncology in New Orleans.

The Allovectin-7 results are interim data from a Phase II registration trial in patients with late-stage metastatic melanoma that has failed other treatments. Allovectin-7 is a DNA/lipid complex containing the gene for the HLA-B7 antigen. In the Phase II study, treatment reduced total tumor burden 50 percent or more in 10 percent of patients, with a current median duration of response exceeding five months. Another 15 percent of patients have achieved stable disease, some with reductions in tumor burden that are significant but did not achieve 50 percent. A Phase III trial in the same indication is also under way.

Phase II interim data for Leuvectin, which delivers a gene for interleukin-2 and is in development for kidney cancer, also were positive. Forty-three percent of the 37 patients evaluated with limited metastatic kidney cancer and mild symptoms experienced clinical activity. Tumor burden was reduced 50 percent or more in 3 patients, with duration of response 12 to 19-plus weeks. Another six achieved stable disease, with duration of response up to 69-plus weeks. Vical also disclosed at ASCO the FDA's designation of Leuvectin as an orphan drug for kidney cancer and the initiation of a second Phase II trial in kidney cancer patients.

Introgen Therapeutics Inc., which earlier this year won regulatory approval to take its adenovirus-delivered p53 gene therapy for cancer into Phase III, presented data from several trials, including interim results from a combination study with radiation in non-small-cell lung cancer. Of the 17 patients entered to date, five manifested local tumor control (greater than 50 percent regression) and had a negative biopsy without evidence of tumor progression at any site. Nine experienced greater than 50 percent regression of their primary tumor and had a biopsy at the conclusion of treatment, which confirmed no active cancer cells at the site treated with gene therapy. Introgen also reported comprehensive safety and tolerance data from Phase I and II trials of the product in squamous cell carcinoma of the head and neck, prostate cancer and NSCLC. Introgen, which is privately held but has registered for an IPO, has partnered the p53 product with Aventis Pharmaceuticals Inc., of Parsippany, N.J.

In other ASCO news:

¿ AltaRex Corp., of Waltham, Mass., presented new data on the anticancer antibodies OvaRex and BrevaRex. In long-term follow-up of 49 relapsed ovarian cancer patients, median survival increased to 18.5 months, compared to the 11.5 months expected. Six patients are still alive four to eight years following initial treatment. The BrevaRex presentation focused on immunology results from a Phase I trial. Those achieving stabilization of the MUC1 antibody antigen had the highest overall immune response.

¿ Antigenics Inc., of Woburn, Mass., announced plans to initiate a randomized Phase III trial of the personalized cancer vaccine Oncophage in renal cell carcinoma. The decision is based in part on findings from a Phase II trial enrolling patients with Stage IV renal cell carcinoma. In that study, the product improved the course of disease in 35 percent of patients. Researchers also presented data from a Phase I/II trial of Oncophage in patients with metastatic gastric carcinoma. Half of the 10 patients who received the vaccine in that trial are alive and disease free at a median of nine months after surgery.

¿ Avax Technologies Inc., of Kansas City, reported Phase I/II ovarian cancer data for O-Vax, an autologous cell vaccine. The new results extend earlier findings indicating the product induces a positive immunological and clinical response in ovarian cancer patients who are refractory to chemotherapy.

¿ Biomira Inc., of Edmonton, Alberta, reported data from two Phase I trials of the BLP25 vaccine. In patients with non-small-cell lung cancer, the product was well tolerated and elicited a cytotoxic T-lymphocyte response in five of 12 evaluable patients with Stage IIIb and Stage IV disease. A trial in recurrent metastatic breast cancer used dendritic cells incubated with BLP25, finding such a therapy safe and feasible.

¿ BioNumerik Pharmaceuticals Inc., of San Antonio, reported positive Phase I data for two compounds: kareniticin BNP1350, a silicon-containing, camptothecin-like agent, and an antifolate called MDAM (gamma-methylene-10-deazaaminopterin). Kareniticin will move into Phase II trials in solid trials and leukemias later this year, with an oral formulation expected to enter the clinic as well. The MDAM results suggest the drug is safer than methotrexate; the company plans to test an oral version in future Phase I trials.

¿ Genta Inc., of Lexington, Mass., presented a review of published data on Genasense (G3139) at an educational session on antisense therapy for cancer. Genasense is an antisense compound targeting bcl-2, a protein that contributes to chemotherapy resistance.

¿ ImClone Systems Inc., of New York, presented preclinical findings on the safety and antiangiogenic activity of IMC-1C11, a chimerized monoclonal antibody that inhibits the KDR receptor, which is the receptor for vascular endothelial growth factor. IMC-1C11 has moved into a human trial in patients with colorectal carcinoma. The company also presented a summary of positive findings from Phase I and ongoing Phase II combination trials that pair IMC-C225, a monoclonal antibody against epidermal growth factor, with chemotherapy to treat advanced refractory cancers. IMC-C225 has entered two Phase III trials for advanced squamous cell head and neck cancer.

¿ Immuno-Designed Molecules SA, of Paris, reported that IDM-1 demonstrated anti-tumor biological activity in a Phase II clinical trial in patients with ovarian cancer. In 14 patients analyzed for efficacy, disease progression was observed in four and stabilization in four. Five patients enjoyed complete response, with no cancer cells upon biopsy, and another three experienced a more than 50 percent reduction of CA125, an ovarian cancer marker.

¿ Isis Pharmaceuticals, of Carlsbad, Calif., presented Phase I/II trial data for ISIS 3521, an antisense cancer drug being tested in patients with non-small-cell lung cancer. Used in combination with carboplatin and paclitaxel, the drug produced significant anti-tumor activity and prolonged survival.

¿ MGI Pharma Inc., of Minneapolis, presented Phase II trial results for irofulven in patients with advanced pancreatic cancer for which gemcitabine has failed. Seven of 26 evaluable patients achieved a six-month survival benefit, one experienced a complete response and another an 84 percent decrease in tumor mass. Irofulven is the first product candidate from MGI's family of acylfulvenes.

¿ Protarga Inc., of Conshohocken, Pa., reported preliminary Phase I results from a novel taxane called Taxoprexin (DHA-paclitaxel), a synthetic small molecule made by linking the paclitaxel to the natural fatty acid DHA (docosahexaenoic acid). Initial patients treated tolerated the drug well, with few side effects.

¿ StressGen Biotechnologies, of Victoria, British Columbia, reported positive Phase I results for HspE7 (SGN00101), a fusion protein drug for human papillomavirus. The drug, now in a Phase II study in women with high-grade cervical dysplasia, was well tolerated and activated T cells.

¿ The Fred Hutchinson Cancer Research Center, of Seattle, reported pooled Phase II data for Mylotarg (gemtuzumab ozogamicin), which has been approved by the FDA to treat relapsed CD33-positive myeloid leukemia in patients age 60 and older. Mylotarg produced remission in 31 percent of patients, a rate comparable to standard chemotherapy combinations, with mild and tolerable side effects. For patients 60 and older, the remission rate was 28 percent. Mylotarg was developed by Celltech Group, of Slough, UK, and is marketed by Wyeth-Ayerst Laboratories, a Radnor, Pa., unit of American Home Products Corp.