LBA34 - FORTIS-M, A Randomized, Double-blind, Placebo-controlled Phase 3 Study of Oral Talactoferrin alfa with Best Supportive Care in Patients with Advance...

Date 01 October 2012
Event ESMO Congress 2012
Session NSCLC metastatic, II
Topics Anti-Cancer Agents & Biologic Therapy
Non-Small-Cell Lung Cancer, Metastatic
Presenter Suresh Ramalingam
Authors S.S. Ramalingam1, J. Crawford2, A. Chang3, C. Manegold4, R. Perez-Soler5, J. Douillard6, N. Thatcher7, F. Barlesi8, T. Owonikoko9, Y. Wang10, P. Pultar11, J. Zhu11, R. Malik10, G. Giaccone12
  • 1Emory University Winship Cancer Institute, 30322 - Atlanta/US
  • 2Dept. Of Medicine/division Of Medical Oncology, Duke University Medical Center, 27710 - Durham/US
  • 3Department Of Medical Oncology, Johns Hopkins Singapore, Singapore/SG
  • 4Dept. Of Surgery, Klinikum Mannheim GmbH, Mannheim/DE
  • 5Department Of Oncology, Montefiore Medical Center, Bronx/US
  • 6Medical Oncology, Centre René Gauducheau (ICO) Institut de Cancerologie de l'Ouest, 44805 - ST HERBLAIN/FR
  • 7Medical Oncology, University of Manchester, M20 4BX - Manchester/UK
  • 8Multidisciplinary Oncology & Therapeutic Innovatio, Hopital Nord, 13915 - Marseille CEDEX 20/FR
  • 9Department Of Hematology And Medical Oncology, Emory University Winship Cancer Institute, 30322 - Atlanta/US
  • 10N/a, Agennix, Inc., 77046 - Houston/US
  • 11N/a, Agennix, Inc., 08540 - Princeton/US
  • 12Medical Oncology Branch, National Cancer Institute, US-20892 - Bethesda/US

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.