Corixa's Melacine Melanoma Vaccine Phase III Clinical Trial Data.

Health/Medical Writers

SEATTLE--(BW HealthWire)--Oct. 30, 2000

Presented At Society of Biological Therapy Meeting

Clinical Benefit for Corixa's Melacine Melanoma Vaccine

Found to be Highest in Patients with Specific HLA Types

Corixa Corporation (Nasdaq:CRXA), a research and development-based biotechnology company, today announced that additional data from its Phase III, randomized trial to evaluate Corixa's therapeutic vaccine Melacine(R), for the treatment of Stage II melanoma, were presented on Saturday Oct. 28, 2000, by the Southwest Oncology Group at the Society of Biological Therapy meeting in Seattle, Wash.

In their presentations on behalf of the Southwest Oncology Group, Drs. Vernon K. Sondak of the University of Michigan Comprehensive Cancer Center and Jeffrey A. Sosman of the University of Illinois at Chicago reported results indicating that the clinical benefit of Melacine vaccination was significantly higher in patients with specific human leukocyte antigen (HLA) phenotypes.

The Phase III clinical trial was conducted by the Southwest Oncology Group with the primary study endpoint being the comparison of disease-free survival in 689 total patients with Stage II melanoma who, following surgical removal of the patient's primary tumor, received adjuvant immunotherapy with Melacine vaccine, versus no adjuvant therapy. As previously presented and reported, Melacine vaccination was found to provide a statistically significant benefit in terms of prolongation of disease free survival in the total patient population. An additional prospectively defined efficacy endpoint was to explore the interaction between the patients' expression of five different HLA genes (HLA-A2, HLA-A28, HLA-B44, HLA-B45, and HLA-C3) and the efficacy of the vaccine. Defining this as an efficacy endpoint was based on early data in phase I/II trials in Stage III and IV melanoma patients in which a possible correlation of response to these five HLA genes was observed. This preliminary data indicated that 38 percent of patients who expressed two or three of the five different HLA genes benefited from Melacine vaccination while only seven percent of the patients who expressed none or only one of the same genes derived clinical benefit. These results suggested that there may be a relationship between a patient's HLA phenotype and response to Melacine or other tumor vaccines.

HLA genes encode proteins that are intimately involved in antigen recognition and processing as well as immune cell activation and function. HLA genes are highly polymorphic and as such, individuals within the population express multiple and different HLA genes. Differential expression of HLA genes is known to be associated with differential immune responses including preponderance of certain autoimmune diseases in patients with specific HLA phenotypes.

New data on the relationship of the HLA phenotype of the patients to their response to Melacine vaccine were presented. HLA phenotype was determined for 80 percent of the 689 stage II melanoma patients in the Southwest Oncology Group study. Disease-free survival was significantly better in vaccinated patients who expressed two or more of the five prospectively defined HLA alleles (p=0.0001) as compared to patients with the same HLA phenotype who were not vaccinated after surgery. The effect was predominantly related to expression of two HLA phenotypes, HLA-A2 and HLA-C3 (p=0.001). These HLA phenotypes are among the most commonly expressed HLA genes in the population, with A2 and C3 being expressed by approximately 46 percent and 29 percent of the clinical trial population, respectively.

The investigators speculated that the association between the patient's disease and the response to the vaccine might be related to the possibility that certain HLA alleles are critical to the binding and presentation of melanoma antigens found within the vaccine.

Initial Phase III data were presented Feb. 17, 2000, by the Southwest Oncology Group at the "Melanoma at the Millennium" meeting in Phoenix, Ariz., indicating that Corixa's Melacine vaccine prolonged disease free survival in patients following surgery for Stage II melanoma and in particular for those patients with thinner (smaller) tumors. On Sept. 27, 2000, Corixa announced its intent to file for regulatory approval of its Melacine melanoma vaccine with the U.S. Food and Drug Administration.

"The highly statistically significant correlation between patient HLA phenotype expression and clinical benefit from Melacine vaccination is intriguing," said Steven Gillis, Ph.D. chairman and chief executive officer of Corixa. "These results mark the first demonstration of such a correlation in the setting of response to a tumor vaccine. As we enter the post-genomic world of therapeutic development, multiple groups have been discussing the delivery of pharmaceuticals in accordance with expression of the polymorphic genetic targets of the drugs themselves. The HLA family was amongst the first polymorphic set of genes ever discovered. Differential HLA gene expression has long been known to be intimately involved in antigen recognition and immune response. Therefore the correlation of clinical benefit post vaccination with patient expression of particular HLA genes was a plausible endpoint to explore even when this landmark tumor vaccine trial was initiated by the Southwest Oncology Group in 1992. We are pleased with the outcome of this analysis and will include these results in our proposed Biological License Application for Melacine."

About Melanoma and Melacine

Malignant melanoma is a highly metastatic and lethal form of skin cancer. It is the most common form of cancer in women between the ages of 25-29 and the second most common form of cancer in women ages 30-34. It is the third most common form of cancer in men ages 35-44. According to the American Cancer Society, cancer of the skin is the most common of all cancers. Melanoma accounts for about 4 percent of skin cancer cases, but causes about 79 percent of skin cancer deaths. The number of new cases of melanoma found in the United States is on the rise. The American Cancer Society predicts that, in the year 2000, there will be 47,700 new cases of melanoma in the United States and about 7,700 deaths resulting from melanoma.

Melacine melanoma vaccine consists of lysed (broken) cells from two human melanoma cell lines combined with Corixa's proprietary Detox(R) adjuvant. Detox adjuvant includes MPL(R) adjuvant (monophosphoryl lipid A) and mycobacterial cell wall skeleton, both of which activate the human immune system in the context of vaccination.

Forward-Looking Statements

Except for the historical information presented, certain matters discussed in this press release are forward-looking statements. Forward-looking statements are based on the opinions and estimates of management at the time the statements are made. They are subject to certain risks and uncertainties that could cause actual results to differ materially from any future results, performance or achievements expressed or implied by such statements. Factors that could affect Corixa's actual results include, but are not limited to the "Factors Affecting Our Operating Results, Our Business and Our Stock Price," described in our Quarterly Report on Form 10-Q filed on August 14, 2000, copies of which are available from our investor relations department. Readers are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date of this release.