LBA34 - Fortis-M, a Randomized, Double-Blind, Placebo-Controlled Phase 3 Study of Oral Talactoferrin Alfa with Best Supportive Care in Patients with Advanced Non-Small Cell Lung Cancer Following Two or More Prior Regimens- by the Fortis-M Study Group

Abstract

ABSTRACT Background Talactoferrin alfa (TLF) is an oral Dendritic Cell Mediated Immunotherapy (DCMI). Based on positive results in two randomized phase II trials in NSCLC, we conducted a phase III study of TLF versus placebo for advanced NSCLC following ≥2 prior systemic therapy regimens (NCT00707304). Methods Inclusion criteria were: age >18 years; failed ≥2 prior systemic regimens (received 1 platinum-based regimen); presence of measureable disease; ECOG performance status 0-2; and life expectancy >12 weeks. Patients were randomly assigned (2:1) to receive TLF (1.5 g oral solution) or placebo BID, each with best supportive care, for a maximum of five 14-week cycles (12 weeks on/2 weeks off). The primary endpoint was overall survival (OS). Secondary endpoints included 6-month and 1-year survival rates, progression-free survival (PFS), objective response rate, and objective disease control rate (DCR), complete or partial response or stable disease). The primary endpoint was analyzed using a stratified log rank test with a 2-sided significance level of 0.05. Results A total of 742 patients (TLF = 497, placebo =245) were enrolled between November 2008 and March 2011 at 163 centers worldwide. Median age was 62 years for TLF and 63 years for placebo; 90% of patients in each group had Stage IV disease; and 56.5% of TLF patients and 58.4% of placebo patients had received ≥3 prior regimens. The median OS for TLF was 7.49 months versus 7.66 months for placebo (HR 1.04, P = 0.6602); and the respective values for PFS were 1.68 and 1.64 months (HR 0.99, P = 0.8829). The DCR was 37.6% for TLF and 38.4% for placebo (P = 0.8336). 87.3% of patients in the TLF arm experienced an adverse event (AEs), 86.0% in the placebo arm; 36.4% of patients had Grade 3-4 AEs in the TLF arm, 35.5% in the placebo arm; and those for serious AEs were 43.7% and 41.7%. Discontinuations due to AEs occurred for 14.5% of TLF patients vs 15.7% for placebo. Conclusions TLF plus best supportive care did not extend OS or PFS vs placebo plus best supportive care in patients with advanced NSCLC. Oral TLF had a safety profile comparable to that for placebo. Disclosure S.S. Ramalingam: I have served on advisory board meetings for Agennix and have received honorarium. J. Crawford: Author has served on advisory board meetings to Agennix and has received honorarium. A. Chang: Author has served on advisory board meetings to Agennix and has received honorarium. C. Manegold: Author has served on advisory board meetings to Agennix and has received honorarium. R. Perez-Soler: Author has served on advisory board meetings to Agennix and has received honorarium. J. Douillard: Author has served on advisory board meetings to Agennix and has received honorarium. N. Thatcher: Author has served on advisory board meetings to Agennix and has received honorarium. F. Barlesi: Author has served on advisory board meetings to Agennix and has received honorarium. Y. Wang: Co-author is an employee and stockholder of Agennix P. Pultar: Co-author is an employee and stockholder in Agennix. J. Zhu: Co-author is an employee and stockholder of Agennix R. Malik: Author is an employee of Agennix and owns stock and stock options with Agennix. All other authors have declared no conflicts of interest.