Vysis Inc.'s test for HER2 gene amplification has won the endorsement of Genentech Inc., maker of Herceptin, a monoclonal antibody treatment for metastatic breast cancer that overexpresses the HER2 protein (human epidermal growth factor receptor-2).

Vysis, of Downer's Grove, Ill., and South San Francisco-based Genentech signed a collaborative agreement under which the Vysis PathVysion HER2 test kit will be used to assess patients for whom Herceptin therapy is being considered.

Dako Corp., of Carpinteria, Calif., has been marketing a competing diagnostic called HercepTest since Herceptin's launch in the fall of 1998. Dako, a subsidiary of Dakopatts A/S, of Copenhagen, Denmark, uses antibodies to measure the amount of HER2 on a cell surface. Dako licensed patent rights and know-how for the test from Genentech.

Vysis' test is already FDA-approved to detect HER2/neu gene amplification as an adjunct to existing clinical and pathologic information used as prognostic factors in node-positive, Stage II breast cancer. Vysis now aims to expand the labeling in breast cancer and additional cancers for which Herceptin is in development. "We expect to make a coordinated FDA submission with Genentech in the near future," said John Bishop, Vysis' president and CEO.

Vysis announced the deal, whose terms were undisclosed, at the American Society for Clinical Oncology meeting in New Orleans, where Genentech presented positive data on PathVysion. The test uses fluorescence in situ hybridization, or FISH, to detect HER2. DNA probes are directly labeled with a fluorescent marker that binds to target DNA or a particular gene within a tumor cell nucleus. The technology allows for a direct visualization of the gene.

Tuesday was a busy news day for Genentech, which also reported positive preliminary Phase II results for Herceptin as a front-line, single-agent therapy in women with previously untreated HER2-positive metastatic breast cancer. The overall response rate was 26 percent, and all responses were seen in patients who overexpressed HER2 at the highest level as measured by immunohistochemistry testing.

The company closed the day with the release of positive preliminary Phase II results for its recombinant humanized monoclonal antibody to vascular endothelial growth factor (rhuMAb-VEGF) in two indications, non-small-cell lung cancer and metastatic breast cancer. Genentech had earlier presented findings for colorectal cancer, the lead indication and the one for which a Phase III trial is slated to begin by the end of the third quarter.

Allos Drug Succeeds In Brain Metastases

Allos Therapeutics Inc., of Denver, reported significant survival improvement in a Phase II trial of RSR13, a small molecule that boosts oxygen release from hemoglobin as a means of heightening radiation sensitivity. The trial combined the drug with cranial radiation therapy in patients with Class II brain metastases. In the open-label, multicenter study, patients treated with the RSR13/radiation combination had a median survival of 6.9 months compared to 4.1 months for similar patients who received only radiation. The control patient outcomes were mined from a clinical database.

The product scored well on several additional endpoints:

¿ The survival rate of RSR13-treated patients at 12 months was 32 percent compared to 15 percent for the database patients.

¿ Analysis using exact case-matched controls showed median survival of 7.3 months with RSR13 plus radiation vs. 3.4 months with radiation alone.

¿ Death due to brain metastases occurred in 9 percent and 37 percent of the RSR13 and database patients, respectively.

¿ Analysis using exact case-matched controls showed that RSR13-treated patients had a 60 percent reduction in risk of death compared to database patients.

¿ Median survival was 14 months for complete responders to RSR13/radiation (10.5 percent of patients), 6.4 months for partial responders (28.1 percent) and 4.1 to 5.4 months in patients with stable disease or non-responders.

In other ASCO news:

¿ Alfacell Corp., of Bloomfield, N.J., reported preliminary results from a Phase III trial of Onconase, a cytotoxic ribonuclease, that show a survival benefit vs. doxorubicin in patients with malignant mesothelioma. The median survival time for Onconase patients was 11.6 months, two months longer than for doxorubicin-treated patients. Several patients treated with Onconase experienced long-term survival.

¿ Alza Corp., of Palo Alto, Calif., and SmithKline Beecham plc, of London, were both pleased with updated results from a Phase III trial comparing SmithKline's Hycamtin (topetecan) to Alza's Doxil (lipsomal doxorubicin) for the treatment of recurrent ovarian cancer. The products had similar results in terms of tumor shrinkage, with Alza touting lower rates of serious complications for its product. SmithKline countered that "the true impact of side effects can only be determined through rigorous quality of life instruments," which were not used in this study.

¿ Aronex Pharmaceuticals Inc., of The Woodlands, Texas, reported that two out of three patients enrolled in an ongoing Phase I/II trial of Atragen have experienced a partial remission. The trial, which has been redesigned, is seeking to define the maximum tolerated dose of Atragen combined with interferon-alpha to treat advanced renal cell cancer.

¿ Cell Genesys Inc., of Foster City, Calif., reported prolongation of disease-free survival in a Phase I trial of the GVAX pancreatic cancer vaccine in 14 patients who received the vaccine following surgery and adjuvant radiation and chemotherapy. Three of eight patients receiving the two highest doses are alive and disease-free more than two years after treatment.

¿ Genta Inc., of Lexington, Mass., reported data from a 35-patient Phase I combination therapy trial employing its Genasense (formerly G3139) and New York-based Bristol-Myers Squibb Co.'s Taxol (paclitaxel). The product was well tolerated with adverse effects similar to those of Taxol alone. Biological data showed that Genasense significantly reduced levels of the Bcl-2 protein, the antisense drug's target. A major clinical response was observed in a patient with bladder cancer that had metastasized to the liver.

¿ Genzyme Molecular Oncology, of Framingham, Mass., reported that the first two patients evaluated for immune response in a Phase I/II melanoma cancer vaccine trial showed evidence of immunity.

¿ Hoffmann-La Roche Inc., of Nutley, N.J., reported encouraging preliminary evidence of antitumor activity in a Phase I trial of Ro 31-7453, an oral cell-cycle inhibitor that in preclinical testing demonstrated activity against chemotherapy-resistant tumors. The trial found a maximum tolerated dose of 200 mg/m2 twice a day for seven days every four weeks. Phase II trials are expected to begin this year.

ImClone Systems Inc., of New York, reported follow-up data from a Phase Ib/IIa study of IMC-C225 and radiation in patients with locally advanced squamous cell head and neck carcinoma. Of 15 evaluable patients, 13 enjoyed a complete response (100 percent tumor regression) and two experienced a partial response (greater than 50 percent regression).

¿ Immunomedics Inc., of Morris Plains, N.J., reported an analysis from an ongoing Phase II trial of epratuzumab, a monoclonal antibody that targets the CD22 receptor on mature and malignant B lymphocytes, including non-Hodgkin's lymphoma. At the optimal dose, 60 percent of 44 assessable patients with low-grade, follicular NHL had an objective response, and half of those were complete responses.

¿ Medarex Inc., of Annandale, N.J., said MDX-210, a bispecific anti-HER2/neu antibody, is a component of partner Immuno-Designed Molecules SA's IDM-1, for which Phase II positive results were presented. Now in Phase III testing, the product consists of Immuno-Designed's MAK (Monocytes-derived Activated Killer) cells associated with MDX-210.

¿ Millennium Pharmaceuticals Inc., of Cambridge, Mass., reported data from two Phase I trials of the proteasome inhibitor LDP-341. One showed a correlation between dosing and proteasome inhibition, and the other demonstrated proteasome inhibition at well-tolerated doses.

¿ NeoRx Corp., of Seattle, reported that 18 of 40 patients with multiple myeloma evaluated thus far in a Phase I/II trial of Skeletal Targeted Therapy achieved complete remission without serious drug-induced toxicity. All patients were treated with high-dose chemotherapy or combination chemotherapy and radiotherapy with gradually increasing doses of STR, followed by stem-cell reinfusion.

¿ Pharmacia Corp., of Bridgewater, N.J., reported preliminary Phase I/II data showing the angiogenesis signaling inhibitor SU5416 may extend the time patients with metastatic colorectal cancer remain free of tumor growth and spread. The product was also well tolerated for at least one year when combined with 5-fluorouracil/leucovorin. Pharmacia gained the product last year when it acquired Sugen, now a wholly owned subsidiary.

¿ Pharmacyclics Inc., of Sunnyvale, Calif., reported on the progress of a Phase III trial of Xcytrin (motexafin gadolinium) Injection, for the treatment of cancer patients with brain metastases. The data presented indicate Xcytrin improves local tumor control in the brain, with few patients experiencing neurocognitive deterioration, or death due to tumor progression.

¿ PharmaMar, of Madrid, reported promising early results from Phase II trials of the marine compound ET-743 (ecteinascindin). In one trial, 47 percent of advanced sarcoma patients treated with the product achieved stable disease or objective response. ET-743 is obtained from the Ecteinascidia turbinate - sea squirts that are encased by tough membranes and live in clusters in the Caribbean and Mediterranean seas.

¿ Progenics Pharmaceuticals Inc., of Keystone, Colo., presented animal findings on dehydroascorbic acid as a treatment for oral mucositis, a frequent side effect of chemotherapy and radiation therapy for head and neck tumors. The product reduced the overall duration of clinically significant lesions by about 50 percent.

¿ Protein Design Labs Inc., of Fremont, Calif., reported preliminary results from a Phase I trial of the Smart 1D10 Antibody in patients with relapsed 1D10-positive non-Hodgkin's B-cell lymphoma. Of 10 patients for whom anti-lymphoma activity data are available, two had partial responses, including one who did not respond to Rituxan. The antibody was well tolerated.

¿ SciClone Pharmaceuticals, of San Mateo, Calif., presented a study showing the immunotherapeutic Zadaxin can significantly improve the quality of life for patients undergoing chemotherapy. Zadaxin has been approved in 20 countries, principally as a treatment for hepatitis B and hepatitis C or as a vaccine adjuvant for patients with a weakened immune system.

¿ SuperGen Inc., of San Ramon, Calif., reported "extremely encouraging" data from a Phase II trial of the oral anticancer agent rubitecan in patients with refractory pancreatic cancer. Median survival for the 15 patients (out of 58 enrolled) who achieved either partial response or stable disease was 10 months, about twice as long as the four to six months typical of patients diagnosed with pancreatic cancer.

¿ Targeted Genetics Corp., of Seattle, presented Phase II trial data and a summary of Phase I data for tgDCC-E1A. Of 20 evaluable patients in the Phase II trial, 45 percent showed objective responses or stabilization of disease and 5 percent experienced complete response.

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