OncoVAX^® Cancer Vaccine Clinical Results

OncoVAX^® Phase IIIA Study (8701) Results in Stage II Colon Cancer

• Statistically significant survival benefit in stage II colon cancer
• Results published in The Lancet

The Company believes that OncoVAX^®, now optimized for dose and regimen, is the first patient-specific vaccine to significantly reduce the risk of stage II colon cancer recurrence after surgical resection. In a Phase IIIa study, OncoVAX^® reduced the risk of recurrence in stage II colon cancer patients from one in three patients to one in ten.

Five clinical studies of OncoVAX^®, including 8701 which established optimum dose and regimen, have been completed as of 2014. 757 subjects with colorectal cancer, of which 720 had colon cancer, have been enrolled in OncoVAX^® trials.

We conducted a small bioequivalency study (2002-01) of 15 patients to ensure the newly developed, sterile manufacturing process did not change the clinical outcome observed in 8701. This was necessary because that study did not require a sterile product. The results of the follow-up study concluded that the immunogenicity of OncoVAX^® was unaffected by the sterilization process.

In these trials, excluding the bioequivalency study, 385 subjects (of the 757 subjects) were randomized to receive OncoVAX^®, of which 353 received at least one vaccination and the other 372 subjects were treated with surgery alone. In addition, subjects with colorectal cancer were enrolled in three separate trials that assessed the effects of ASI with OncoVAX^® in combination with chemotherapy as adjuvant therapy to surgical resection. Lastly, two trials have also been performed using autologous tumor cells/BCG in melanoma (n=86) and renal cell carcinoma (n=14).

OncoVAX^® Phase IIIA Results in Stage II Colon Cancer

The incidence of Stage II colon cancer is now 70% of the total number of patients that present each year in the United States and Western Europe.  The total number of patients in these two regions in 2020 was 240,000.  Thus about 170,000 would present with Stage 2 and the majority would be assessable for OncoVAX.  According to the NCCP, the standard of care for these patients is surgical resection.  Thus far, no other treatment adjunct to surgery has shown significant improvement in Recurrence-free survival. Micrometastases or tumor cell seeding, while not readily detectable after surgery by conventional histopathologic techniques, are generally responsible for disease recurrence and the eventual death of colon cancer patients. The histopathological detection of tumors in lymph nodes is, by definition, the hallmark diagnostic criterion for stage III disease. Although not detectable by conventional pathological methods, micrometastases in regional lymph nodes in patients with stage II cancer have now been detected by molecular techniques such as polymerase chain reaction (PCR). These occult micrometastases have been detected in one or more lymph nodes in 54% of stage II patients. Analysis of the relationship between PCR-detectable metastases and survival has resulted in an adjusted 5-year survival (based on cancer-related deaths only) of 91% in patients without micrometastases and 50% in patients with micrometastases (p=0.02), with observed 5-year survival rates of 75% and 36%, respectively (p=0.03).12 Hence, new methods of treatment to eliminate micrometastases in patients with stage 2 colon cancer and thereby delay or prevent recurrence are particularly urgent given the increasing incidence of stage II colon cancer.  While the average age of patients with Stage 2 colon cancer in our 1995 to 2000 phase IIIA clinical trial was 65 years of age.  Today, the onset of early-onset colon cancer diagnosed in patients under the age of 50 years has been increasing around the world.

 Phase IIIA, ACTIVE, 8701 trial in colon cancer with second generation OncoVAX. This 254-patient study, which has allowed Vaccinogen to make efficacy claims for its current version of OncoVAX and is called the ACTIVE study by the company, had its results published in The Lancet in January 1999. In this study the investigators used 10⁷ BCG organisms for the first two doses and tumor cells alone in the third vaccination.  In addition, a booster vaccination of tumor cells alone was added at six months after surgery with 10⁷ irradiated autologous tumor cells. Over a median follow-up period of 5.3 years there was a 44% risk reduction for recurrence for patients that received OncoVAX (p=0.023), but only patients who had stage II disease benefited. For these patients the risk of recurrence was cut by 61%. The cost of the product was subsequently studied by medical technology assessment specialists at the Erasmus University Medical Center in Rotterdam who reported ‘impressive health economics benefits’ in a paper in Vaccine.  In 2012 the investigators revisited the data to see if there were different outcomes for patients with microsatellite unstable versus stable colon cancer. In the process they tracked event-free survival for the study population out to 15 years, finding a hazard ratio for the treatment group of 0.62 (p=0.033).