Melanoma

According to the American Cancer Society, 9,000 people died in the U.S. of melanoma in 2009. Prevalence of Stage III and Stage IV disease is 120,000 and median survival for Stage IV disease is six months.

Treatment of melanoma depends on the stage of the disease with surgical resection being effective in the early stages of the disease. However, survival rates for the later Stage III and Stage IV patients are poor, reflecting the lack of effective drugs for recurrent or metastatic disease. Current systemic therapies are not generally effective in terms of generating durable responses or in impacting survival. As a result, many patients presenting with metastatic disease are directly enrolled into a clinical trial. The vast majority of experimental therapies to date have failed to show more than a single digit durable response rate.

Phase 2 Melanoma Study Results

The results are summarized in the poster below and were published in the Journal of Clinical Oncology, Vol 27, 2009: pp. 5763-5771 in late 2009.

The Phase 2 trial enrolled 50 patients with Stage IIIc (10 patients) and Stage IV melanoma (40 patients) who were treated with OncoVEXGM-CSF as a stand-alone therapy. The trial was designed to measure overall objective response, which is defined as a complete response, where disease is completely eliminated, or partial response, where there is a more than 30% reduction in disease burden. The vast majority of patients who entered the study had progressive disease after having failed conventional and experimental prior therapies. The following results were obtained

• The overall response rate was 28%.
• Ten patients (20%) had a complete response.
• Four patients (10%) had a partial response.
• Responses occurred in injected and distant sites including visceral organs
• 10 further patients (20%) had stable disease for more than three months.
• 92% of responses were maintained for 7-31 months (now 7-48 months).
• Two additional patients had a complete response after surgery.
• Overall survival at one year was 58% and 52% at two years.

[Phase II results poster]

"We believe that OncoVEXGM-CSF is the most advanced clinical development program globally using viruses for cancer therapy, and we are committed to the further evaluation of OncoVEXGM-CSF for the treatment of metastatic melanoma and other solid tumors," said
Robert Coffin, PhD, Founder & Chief Technology Officer of BioVex.      

OPTiM™ Phase 3 Study

BioVex began a multi-national, randomized Phase 3 OPTiM Study in May 2009 to assess the efficacy and safety of treatment with OncoVEXGM-CSF as compared to subcutaneously administered GM-CSF in patients with unresectable Stage III (b-c) and Stage IV (M1a-c) melanoma.  The primary endpoint is the rate of durable (maintained for six months) objective response. A total of 360 patients will be enrolled (240 to the OncoVEX arm and 120 to the control arm). The study design was agreed with the FDA under the Special Protocol Assessment (SPA) process, which provides agreement with the FDA that the trial’s design, clinical endpoints and statistical analysis, if the study is successful, are appropriate to be used as the basis for regulatory approval.

[Visit the OPTiM Trial Site]

 

Head and Neck Cancer

Squamous cell carcinoma of the head and neck accounts for 47,000 new cases (3% of all new cancer cases and 2% of all cancer deaths) in the United States annually; it is the fifth most common malignancy worldwide (an estimated 644,000 new cases annually).

Patients with locally advanced tumors are best treated with concurrent chemoradiation, with planned neck dissection indicated in certain patients. Despite aggressive treatment of locally advanced disease loco-regional recurrences develop in 30% of patients and distant metastases in 20%. Aggressive combined modality therapy may be frequently associated with debility, and numerous physical and psychological symptoms including pain, dysphagia, weight loss, disfigurement, depression, and xerostomia (dry mouth). As a result, new and improved, and less toxic therapies for head and neck cancer are urgently required.

Patients with squamous cell carcinoma of the head and neck often present with locally advanced, bulky disease that is too large, or too close to vital organs, to remove surgically. These patients typically undergo combination radiation and chemotherapy treatment, with in some cases additional surgery. Patients who present with tumor containing lymph nodes are particularly difficult to treat and approximately half of these patients relapse within two years.

Phase I/II Study

In a Phase I/II study, OncoVEXGM-CSF was administered by direct injection, at three dose levels, into tumor containing lymph nodes in combination with standard first line chemo radiotherapy every three weeks for four cycles. All patients then went for surgery. Of the 17 patients enrolled, 16 had Stage IV N2 or N3 disease. OncoVEXGM-CSF was shown to be well tolerated with no significant side effects in addition to those associated with chemoradiation. With respect to efficacy, 93% of patients had a complete pathological response at surgery, with five patients achieving a complete response after only 2 or 3 virus doses. No patient to date has had a loco-regional recurrence in the neck at a median follow up of 30 months, and the disease specific survival rate is currently 82%.

[poster summarizing the results]

Phase III Study Design

The Company is currently preparing for a Phase 3 study in squamous cell carcinoma of the head and neck. The Phase III study design agreed with the FDA follows directly from the design of the previous study. The Phase III study will also enroll previously untreated patients with locally advanced disease. The primary objective of the study will be to demonstrate a statistically significant increase in 2 year event free survival (i.e. relapse, progression, or death) for patients treated with chemoradiation together with OncoVEXGM-CSF as compared to patients treated with chemoradiation alone. The study will involve approximately 400 patients with approximately 200 in each arm.

Pancreatic Cancer

In a dose escalating Phase I study in pancreatic cancer local responses were observed in all patients after titrating up to an efficacious dose level. Approximately 75% of pancreatic cancer tumors are inoperable at the time of diagnosis and, even following chemotherapy and radiation, one-year survival rates are less than 50% and five-year survival rates are less than 5%.

OncoVEX Phase I Trial in Pancreatic Cancer