Oral talactoferrin extends survival in patients with refractory NSCLC in a randomized, placebo-controlled, phase 2 trial

Abstract

7540 Background: Talactoferrin alfa (TLF), an immunomodulatory protein with a novel anti-cancer mechanism of action, was active preclinically and in non-small cell lung cancer (NSCLC) patients in Phase 1b studies. Randomized Phase 2 studies in NSCLC were conducted with TLF as a single agent and combined with chemotherapy. The 110-patient combination therapy study, which was previously presented (ASCO 2006, #7095), met its primary endpoint with an improved BOR over chemotherapy alone. We now present results from the placebo- controlled single agent study. Methods: 100 Stage IIIB/IV NSCLC patients who had progressed after first or second line therapy were enrolled at 10 leading Indian cancer centers, and randomized to receive best supportive care plus either oral TLF (1.5 g bid) or placebo. TLF/placebo was administered until disease progression, for up to three 14-week cycles (12 weeks on, 2 weeks off), in a centrally monitored trial. The primary endpoint was overall survival (OS) with 80% power to detect an improvement in median OS with an a=0.05. Results: All patients had previously received a 1st line platinum based regimen; 26 also received 2nd line therapy. The TLF and placebo arms enrolled 47 and 53 patients, respectively. Baseline characteristics were similar in both groups, including proportion of patients receiving 1 or 2 prior regimens. All patients were included in the Intent To Treat (ITT) analysis. The trial met its primary endpoint with a 55% increase (2.1 month; p<0.05) in median OS. TLF was well tolerated. Adverse Events (AEs) were generally mild. No drug- related SAEs were reported. Incidence of AEs and Grade 3/4 AEs was similar in both arms. Conclusion: Oral talactoferrin, a promising new anti-cancer agent, significantly improved survival in patients with refractory NSCLC in this randomized, placebo-controlled trial. TLF was well tolerated in this population. Given its favorable toxicity profile, TLF may be particularly attractive in refractory patients with poor performance status. [Table: see text] [Table: see text]

A Randomized, Double-Blind, Placebo-Controlled, Phase II Study of Oral Talactoferrin in Combination with Carboplatin and Paclitaxel in Previously Untreated Locally Advanced or Metastatic Non-small Cell Lung Cancer

“…However, in a follow-on trial designed to detect improvements in PFS or OS, it would be desirable to continue TLF/placebo until disease progression, particularly in view of significant OS improvements reported recently with single-agent TLF. 15 The median age of patients enrolled in this trial (approximately 55 years of age) is consistent with that reported in the literature for Indian patients with NSCLC 17 and is lower than the age of patients typically enrolled in clinical trials in Western populations.…”

“…A similar reduction in AEs and grade 3/4 AEs was also observed in a second double-blind, placebo-controlled TLF trial-TLF monotherapy in patients with refractory NSCLC. 15 The majority of the AE reductions were in the four areas where reductions were expected based on lactoferrin's biological activities and previously available data. One major group of AE reductions was in thoraco-respiratory signs and symptoms, which are largely attributable to the NSCLC disease process itself.…”

“…The addition of oral TLF to standard supportive care resulted in a 2.4 month, 65% improvement in median OS (3.7-6.1 months; one-tailed p ϭ 0.04) relative to patients receiving placebo. 15 Single-agent activity was also observed in a phase II trial in renal cell cancer patients who had failed previous chemotherapy. 16 Based on encouraging early data with oral TLF and its novel immunomodulatory mechanism of action, we initiated this randomized, double-blind, placebo-controlled phase II combination trial in NSCLC patients.…”

The role of talactoferrin alfa in the treatment of non-small cell lung cancer

“…No drug-related serious AEs were reported. The incidence of AEs and grade 3 AEs were similar in both treatment arms [27].…”

“…Two company sponsored trials (Agennix) have been conducted in patients with NSCLC. The first trial (LF-0201) was a randomized, double-blind, placebo-controlled, Phase II study of talactoferrin monotherapy in patients with locally advanced or metastatic NSCLC (Stage IIIB/IV NSCLC) who had failed first-or second-line chemotherapy [27]. A total of 100 patients were enrolled at 10 cancer centers in India and received one vial twice a day of either talactoferrin (1.5 g) or placebo given for up to three 14-week cycles of 12 consecutive weeks on followed by two weeks off study drug.…”