AVAX Presents Results of a Dose-Response Study of MVax at American Society of Clinical Oncology (ASCO)
The presentation, entitled, "Dose-response study of a cryopreserved, autologous, hapten-modified melanoma vaccine (MVax(R))," analyzed the safety and immunological efficacy of MVax in 82 patients with Stage III or IV metastatic melanoma. Patients were blindly assigned to one of four dosage groups: 5 million, 2.5 million, 0.5 million or zero (control arm) melanoma cells per dose. In all groups MVax was administered according to a previously defined optimum treatment schedule. The immunological endpoint was the development of delayed-type hypersensitivity (DTH) to autologous, hapten-modified melanoma cells. DTH is a measure of immunity, which AVAX believes is a surrogate marker of MVax's efficacy. All eligible patients had negative DTH prior to MVax administration.
Using a Simon, two-stage analysis the high dose arm (5 million cells) was effective: 23/30 patients developed positive DTH to autologous, DNP-modified melanoma cells and 9/25 to autologous, unmodified melanoma cells. These proportions of positive responses were statistically indistinguishable from the DTH response rate observed in previous studies of MVax conducted at Thomas Jefferson University. In contrast, the zero and medium doses were ineffective, and the low dose was borderline. Moreover, a plot of the dose of MVax administered versus the intensity of the DTH response induced showed a strong correlation: the higher the dose, the larger the DTH.
"This study provides critical information about the lower end of the MVax dose-response curve," commented David Berd, Chief Medical Officer of AVAX. "It allows us to rationally set the dose for phase III, which is 8 to 20 million cells. In addition, it forms a bridge to previous studies of MVax that were performed in more than 400 patients at Jefferson over the past 15 years."
As expected, MVax had an excellent safety profile. Adverse events were identical to what was observed in previous trials and no serious adverse events related to MVAX were observed.
MVax(R) Phase III Registration Study - MVALDI trial
AVAX's ongoing Phase III Registration, MVALDI trial examines survival and anti-tumor response rate using modified response evaluation criteria in solid tumors (modified RECIST criteria) in Stage IV melanoma patients with soft tissue or lung metastasis. The Phase III registration trial is being conducted under a Special Protocol Assessment (SPA) agreement with the U.S. Food and Drug Administration (FDA) for MVax(R) and in agreement with the FDA the company will be eligible to file for accelerated approval of MVax(R) based upon achieving a response rate endpoint. The double blind, randomized trial is expected to enroll up to 387 patients to be accrued over a period of 24 months. Patients are randomized on a two to one basis to the treatment arm or control arm, respectively. The treatment arm consists of MVax followed by a regimen of low dose IL-2; the control arm consists of placebo vaccine followed by low dose IL-2. Both treatment and control arms include BCG and low dose cyclophosphamide.
MVax(R) in Metastatic Melanoma
In a phase 2 clinical study published in the International Journal of Cancer, MVax(R) induced tumor shrinkage in 11/83 patients with surgically incurable stage IV melanoma. In a subsequent paper published by Dr. Michal Lotem in the British Journal of Cancer (British Journal of Cancer 2004, 90 773-780) patients treated with their DNP modified tumor cells, using manufacturing techniques similar to MVax(R), followed by administration of low dose interleukin-2, achieved a response rate of 35%. These results were confirmed in a subsequent study conducted by the same investigator that showed a 32% response rate, including 13% complete responses and 19% partial responses.
MVax(R) in Stage III Melanoma
MVax(R) was the subject of a publication in the Journal of Clinical Oncology that discussed 214 Stage III melanoma patients that were treated with a regimen of MVax(R) post surgery. No patients were lost to follow-up and they were split between Stage IIIb & Stage IIIc melanoma. All patients on study had completed follow-up and the reported five-year survival rate was 45%. This compares to five-year survival published in similar patient populations who underwent surgery alone of 22%. In addition, the data showed a significant correlation between survival and delayed-type hypersensitivity (DTH) responsiveness to patients' unmodified tumor cells (P less than .001). The journal commissioned an editorial on the publication. In a separate study of a similar patient population using a DNP-modified tumor cell vaccine (British Journal of Cancer 2002 May 20; 86(10): 1534-9), Lotem also showed a positive relationship between survival and DTH to melanoma cells.
Cancer of the skin is the most common of cancers while melanoma accounts for approximately 3% of skin cancer cases. According to the SEER CanQuest Database and the American Cancer Society, in the U.S. for 2007 it is estimated there will be 59,940 new cases of melanoma with an expected number of deaths from melanoma of 8,110. The estimated prevalence of melanoma in the U.S. in 2007 is 396,242 cases.
Further information on the Clinical Study
To obtain further information on the phase III clinical study, please visit www.clinicaltrials.gov and look up MVax or use study identifier NCT00477906. Additionally, the study has been assigned eudraCT number 2007-004406-26 by the EMEA. You may also contact Dr. David Berd or Ellen Bloome, RN at AVAX Technologies, Inc., 2000 Hamilton Street, Suite 204, Philadelphia, PA 19130 (215) 241-9760.
About AVAX Technologies, Inc.
AVAX Technologies, Inc. is a biotechnology company with operations in the United States and Europe. The Company is engaged in the research, clinical and commercial development of biological products and cancer therapeutics. AVAX's AC Vaccine platform is a therapeutic cancer vaccine. In addition, the Company performs contract-manufacturing services for biological products for other pharmaceutical and biotechnology companies.
Except for statements that are historical, the statements in this release are "forward-looking" statements that are made pursuant to the safe harbor provisions of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934. Forward-looking statements involve significant risks and uncertainties, and in light of the significant uncertainties inherent in such statements, the inclusion of such information should not be regarded as a representation by AVAX that the objectives and plans of the Company will be achieved. In fact, actual results could differ materially from those contemplated by such forward-looking statements. Many important factors affect the Company's prospects, including (1) risk associated with a change in executive management of the Company, (2) the immediate need to obtain additional funding to continue to finance the Company's development plans, (3) the results of clinical and laboratory testing of its vaccine technologies, (4) possible future FDA or AFSSAPS questions regarding the Company's products and manufacturing processes, (5) exchange rate risks associated with financing the Company in U.S. dollars but funding significant operating expenses in Europe with Euro's, (6) the Company's ability to maintain its rights under license agreements and to meet funding requirements under its license agreements, (7) the Company's ability to demonstrate the safety and efficacy of product candidates at each stage of development and to meet applicable regulatory standards and receive required regulatory approvals, as well as other risks detailed from time to time in AVAX's public disclosure filings with the Securities and Exchange Commission, including its Annual Report on Form 10-KSB. AVAX does not undertake any obligation to release publicly any revisions to these forward-looking statements or to reflect the occurrence of unanticipated events.
AVAX Technologies, Inc.
Dr. David Berd
Chief Medical Officer
Posted: June 2008