Agennix’s Phase II NSCLC trial meets study end point

The monotherapy trial, which compared single-agent oral talactoferrin to placebo in patients with NSCLC who had failed previous chemotherapy, met its primary endpoint of improvement in overall survival. Secondary efficacy endpoints also showed improvement consistent with the primary endpoint results. Oral talactoferrin was well tolerated in this patient population with fewer adverse events observed in the talactoferrin arm. This was the second successful, randomized, double-blind, placebo- controlled trial with oral talactoferrin in NSCLC. The first was with talactoferrin in combination with first-line chemotherapy.

The study met its pre-specified primary endpoint – improvement in overall survival. In the 100-patient intent-to-treat (ITT) population, median overall survival was 65% higher in the talactoferrin group compared to the placebo group – 6.1 months versus 3.7 months (hazard ratio=0.68; p=0.0404). In the 81-patient prospectively-defined evaluable population, the median overall survival was 80% higher in the talactoferrin group compared to the placebo group – 7.9 months versus 4.4 months (hazard ratio=0.59; p=0.0171). The six-month survival rate in the ITT population was also significantly better in the talactoferrin group (49%) compared to the placebo group (28%; p=0.0276). Overall survival improvement trends were consistently observed across subsets of patients grouped by major prognostic factors, including disease stage, performance status, and line of therapy. Positive trends were also observed on the secondary endpoints including progression-free survival and disease control rate. In addition to the efficacy improvements, oral talactoferrin was well tolerated in this group of patients with previously treated NSCLC.

Building on the results of the two positive Phase II studies, preparations are underway for Phase III trials with talactoferrin in two NSCLC indications: first-line in combination with chemotherapy, and monotherapy in patients who have failed two or more previous therapies. The pivotal Phase III, multinational, randomized, double-blind, placebo- controlled monotherapy study will enroll 720 patients with Stage IIIB or IV NSCLC who have failed two or more previous therapies. Patients will receive standard supportive care and be randomly assigned (2:1) to receive single- agent treatment with either oral talactoferrin or placebo until disease progression. Overall survival will be the primary endpoint for approval. Secondary endpoints include adverse event reductions, progression-free survival, confirmed response rate, duration of response, disease control rate and safety.

The Phase III NSCLC monotherapy trial will be conducted concurrently with the pivotal Phase III first-line combination with chemotherapy NSCLC trial. Both studies will be conducted at many of the same sites and in partnership with the same global contract research organization. The first-line Phase III trial is also supported by a positive double-blind, placebo-controlled Phase II trial. For the first-line indication, Agennix has been granted a special protocol assessment and fast track designation from the FDA, and has received favorable scientific advice from the EMEA. Both Phase III studies are expected to be active and recruiting in mid-2008.