CLINICAL TRIALS

A clinical trial is a research study to answer specific questions about new drugs or treatments for disease. Clinical trials are used to determine whether new treatments are both safe and effective in humans. These trials generally occur after extensive work in the laboratory and in animal studies. Regulated by the Food and Drug Administration (FDA) and other regulatory agencies around the world, carefully conducted clinical trials are an established way to find treatments that are safe and effective.

Our previous clinical trials for the AC Vaccine have concentrated on melanoma, ovarian carcinoma, which are our primary indications, and non-small cell lung cancer.

AC Vaccine^® Technology Platform

AVAX's utilizes its Autologous Cell (AC) Therapeutic Vaccine platform for the development of products to be used to treat patients with cancer. The idea behind the AC Vaccine technology is to re-educate the patient's immune system to recognize as foreign the cancer cells that are metastasizing and growing in the patient's body outside of the regulation by the patient's immune system. AVAX's lead product is MVax®, the AC Vaccine technology for the treatment of patients with melanoma. AVAX feels that its technology platform has broad applicability to multiple cancers.

Through extensive clinical development AVAX has determined the optimal regimen for administering the AC Vaccine.

MVax^® for the Treatment of Melanoma

AVAX's Phase III Study: MVALDI

AVAX has launched an International Phase III Registration trial entitled "Comparison of MVax® plus Low Dose Interleukin-2 versus Placebo Vaccine plus Low Dose Interleukin-2 in Patients with Stage IV Melanoma". The study, which has initiated enrollment, is recruiting centers in the U.S., Europe and Israel. The Company will consider adding additional sites and countries as the study progresses.

Registration study enrollment commenced in November 2007. The study is the subject of a Special Protocol Assessment Agreement (SPA) with the U.S. FDA. An SPA is a written agreement between AVAX and the FDA regarding the trial design, surrogate endpoints to be used as a basis of filing for accelerated approval of MVax®, and the statistical analysis plan necessary to support the full regulatory approval of MVax®. An SPA agreement is binding upon the sponsor and the agency.

The Phase III study will enroll up to 387 patients with stage IV melanoma, who will be assigned in a double-blind fashion at a 2:1 ratio to MVax® pt or Placebo vaccine. The MVax® arm will consist of an initial dose of MVax® pt (autologous DNP-modified tumor cells) followed by cyclophosphamide (CY) and then six weekly doses of MVax® administered with Bacillus of Calmette and Guerin (BCG). Following vaccine administration patients will receive a specific schedule of low dose IL-2. Patients assigned to the control group will receive a treatment identical to the MVax® group, except that a Placebo Vaccine will replace MVax®. The primary endpoints of the study are best overall anti-tumor response rate and the percentage of patients surviving at least 2 years. Secondary endpoints of the study will include overall survival time, response duration, percentage complete and partial responses, progression free survival and treatment related adverse events.

The data analysis plan for the study includes an interim analysis of Best Overall Response Rate (complete and partial) to be performed when half the patients (194 patients) have completed assessment of their best anti-tumor response. The comparison of the best overall response rates for the MVax® and control groups will be used as the basis for an expected initial Biologics License Application (BLA) submission under 21 CFR 601 Subpart E, which allows for accelerated approval using a surrogate endpoint in certain life threatening diseases. The analysis of overall survival will be performed when patients have reached the two-year point.

The protocol is based on published data showing that administration of MVax® alone can induce clinically meaningful anti-tumor responses in patients with stage IV melanoma. Moreover, data from other clinical trials and from animal models suggest that the addition of low dose IL2, properly timed, can greatly increase anti-tumor response rates. Finally, because IL2 will be given at a low dose, AVAX expects that its use will not be limited by serious toxicity.

Phase I/II Study

AVAX recently announced the successful completion of its Phase I/II study of the treatment of patients with Stage III & IV melanoma. The results of this study will be presented at the 2008 American Society of Clinical Oncology (ASCO) Meeting in Chicago.

The study was designed to evaluate four doses of MVax® with dose defined by the number of cells injected in each vaccine; the doses tested were: 5x106 cells (high dose), 2.5x106 cells (medium dose), 0.5x106 cells (low dose), and 0 cells (zero dose). All dosages were administered according to a previously developed optimum schedule, which included an induction dose without adjuvant followed by low dose cyclophosphamide and then 6 doses admixed with the immunological adjuvant, BCG, Endpoints of the study were safety and an immunological endpoint of delayed-type hypersensitivity (DTH), which is a T-cell-mediated immune response to autologous melanoma cells. The study was also designed to demonstrate that the frozen formulation of MVax® is bio-equivalent to the original, freshly-prepared autologous, hapten-modified vaccine.

The high dose arm of vaccine was highly effective immunologically with positive DTH responses to hapten-modified autologous melanoma cells observed in 22/29 (76%) patients following a course of MVax®; baseline DTH responses were negative, as a condition of enrollment. In contrast, the zero dose arm was ineffective. Linear regression analysis of DTH responses of all evaluable patients showed a clear dose-response relationship when DTH responses for each patient were plotted against the MVax® dose received. These results are important, because previously published studies by AVAX and others showed a statistically significant relationship was seen between survival and induction of DTH after MVax® administration.

The safety profile of MVax® appeared to be very favorable. There were no Serious Adverse Events attributed to MVax®. Non-serious adverse events were similar to what has been observed in previous trials of the autologous, haptenized vaccine: mild-moderate injection site reactions in all patients, mild nausea from cyclophosphamide in some patients, and mild constitutional symptoms, such as fatigue, in some patients after MVax® administration.

LungVax^® for the Treatment of Non Small Cell Lung Cancer

This is the first ever study conducted with the AC Vaccine in the treatment of Non Small Cell Lung Cancer. The study is treating patients with Stage I, II & III disease that undergo complete surgical resection. The vaccine is given to the patients prior to any other post surgical intervention (chemotherapy, etc.).

The study is designed to evaluate three doses of LungVax® with dose defined by the number of cells injected in each vaccine; the doses tested are: 5x106 cells (high dose), 2.5x106 cells (medium dose), and 0.5x106 cells (low dose). All dosages are administered according to a previously developed optimum schedule, which includes an induction dose without adjuvant followed by low dose cyclophosphamide and then 6 doses admixed with the immunological adjuvant, BCG, Endpoints of the study are safety and an immunological endpoint of delayed-type hypersensitivity (DTH), which is a T-cell-mediated immune response to autologous lung cancer cells.

Planned Future Studies

OVax^® for the Treatment of Ovarian Cancer

In data previously presented on the use of OVax®, two phase I-II clinical trials were performed. In the first trial, 9 evaluable patients with newly diagnosed adenocarcinoma of the ovary underwent standard debulking surgery plus six cycles of chemotherapy (taxol + platinum) prior to receiving OVax®. In the second trial, 13 evaluable patients with bulky, chemotherapy-refractory disease were treated. Positive DTH (5-mm induration) to autologous DNP-modified tumor cells was elicited in 19 of 22 patients (median = 14-mm induration). More importantly DTH to unmodified tumor cells was induced in 17 of 22 patients and (median = 6).

Unexpectedly, a clinical responses was observed as well: one patient, who had previously had excision of a peritoneal tumor, exhibited complete regression of a residual peritoneal mass by computed tomography (CT) and a concomitant fall in serum CA-125 from 65 to 6. Both the CT and CA-125 responses were maintained for 6 months.

AVAX intends to activate a Phase I/II IND for the treatment of Stage III & IV Ovarian Cancer patients who have relapsed following chemotherapy. In the planned study, AVAX will evaluate patients for safety and immunological responses, as measured by Delayed Type Hypersensitivity (DTH).

© 2008 AVAX Technologies, Inc. | Terms