Preliminary Results of Phase 2 Clinical Trial in Patients Treated with First-Line Chemotherapy for Non-Small Cell Lung Cancer (Study OGX-011-05)

This trial was designed to evaluate the safety and efficacy of custirsen (OGX 011) in combination with gemcitabine and a platinum agent (cisplatin or carboplatin) as first-line chemotherapy in patients with advanced non-small cell lung cancer. The three drugs were administered over a 21-day cycle. Patients could receive up to six cycles of therapy. A total of 81 patients were treated, of which 82% of the patients had Stage IV disease at enrollment. Patients are currently being followed for survival.

The primary objective of this Phase 2 clinical trial was to estimate objective response rates and further describe the safety profile of weekly custirsen treatment in combination with a gemcitabine and platinum based regimen in patients with metastatic or locally advanced non-small cell lung cancer. Secondary objectives included: (a) measuring progression-free survival and overall survival and (b) measuring the effect of custirsen treatment on serum clusterin levels and, whenever possible, within accessible tumors.

The preliminary results of this study were presented by Janessa Laskin, M.D., a medical oncologist at the BC Cancer Agency, at the 2007 Annual Meeting of the American Society of Clinical Oncology (ASCO) in Chicago.

Patients in this trial received a median of 4 treatment cycles. Weekly custirsen treatment in combination with gemcitabine and platinum regimen was well tolerated.

Survival results have been updated since the meeting and support the preliminary results presented by Dr. Laskin. The median follow-up as of May 1, 2008 is 24.0 months. The median survival remains at 14.1 months (0.13 – 33.7 months) with 54% of patients having survived one year or more. These data compare favorably with prior published results from randomized clinical trials using gemcitabine and cisplatin or carboplatin which have reported median survival times of 8 to 10.8 months and one-year survival rates of 33% to 43%.

The following table summarizes the response to therapy for measurable disease in the patients who were evaluable for response.

Although tumor specimens were not available to assess the effect of custirsen treatment on tissue clusterin levels, serum clusterin levels were decreased after treatment with custirsen.

Patients in this clinical trial experienced various adverse events, the majority of which are known to be associated with the other treatments in the protocol (gemcitabine/platinum-based chemotherapy) and the disease. The most common moderate or severe adverse events were dyspnea, fatigue, nausea or vomiting, anorexia, chest pain and pleural effusions. Decreased blood cell counts, sodium levels and potassium levels were also observed.

We believe that these preliminary results warrant a Phase 3 or registration trial of custirsen in combination with a platinum and gemcitabine regimen as first-line chemotherapy for advanced non-small cell lung cancer. Our assessment is primarily based on the survival duration observed in this clinical trial. The key results are:

• The median overall survival was 14.1 months which is longer than the median overall survival reported in prior published results (8 to 10.8 months) from randomized clinical trials using gemcitabine and a platinum chemotherapy for first-line chemotherapy;
• 54% of patients survived at least 1 year which is a higher frequency than the one-year survival rate reported in prior published results (33% to 43%) from randomized clinical trials using gemcitabine and a platinum chemotherapy for first-line chemotherapy;
• 73% of patients achieved overall Disease Control; and
• 50% of patients were able to receive 4 or more cycles of chemotherapy with 25% completing all 6 cycles of chemotherapy.