Allos Therapeutics, Inc. (Nasdaq: ALTH) announced the completion of patient enrollment in the Company's randomized Phase 2b clinical trial comparing pralatrexate to erlotinib (Tarceva®) in patients with Stage IIIB/IV non-small cell lung cancer (NSCLC) who are, or have been, cigarette smokers who have failed treatment with at least one prior platinum-based chemotherapy regimen.
"Advanced non-small cell lung cancer represents an area of high unmet medical need where we believe pralatrexate has the potential to offer a new treatment option," said Pablo J. Cagnoni, M.D., chief medical officer of Allos Therapeutics. "We are pleased with the strong interest in this trial, having enrolled 201 patients in 18 months. The objective of this Phase 2b trial is to assess the treatment effect of pralatrexate in certain pre-specified subsets of patients with advanced non-small cell lung cancer where we believe the agent has the potential to provide clinical benefit."
This randomized, open-label, international, multi-center Phase 2b trial was initiated in January 2008 and enrolled 201 patients. The objective of the trial is to compare the efficacy of pralatrexate to that of erlotinib in patients with Stage IIIB/IV NSCLC who are, or have been, cigarette smokers who have failed treatment with at least one prior platinum-based chemotherapy regimen, including subsets of light and heavy smokers, as well as current and former smokers. Per the protocol, the primary endpoint is overall survival. Response rate, progression-free survival and the safety and tolerability of pralatrexate will also be assessed. Patients were randomized 1:1 to receive either pralatrexate or erlotinib. Patients randomized to the pralatrexate arm received pralatrexate as an intravenous (IV) push administered on days 1 and 15 of a 28-day cycle. The initial dose of pralatrexate was 190 mg/m2. Patients randomized to the erlotinib arm received erlotinib 150 mg/day orally in a 28-day cycle. Patients in both arms received concurrent vitamin therapy of B12 and folic acid. The primary survival analysis will be performed when a pre-specified number of events have occurred in all randomized patients.
About Pralatrexate
Pralatrexate is a targeted antifolate designed to accumulate preferentially in cancer cells. Based on preclinical studies, the Company believes that pralatrexate selectively enters cells expressing RFC-1, a protein that is over-expressed on certain cancer cells compared to normal cells. Once inside cancer cells, pralatrexate is efficiently polyglutamylated, which leads to high intracellular drug retention. Polyglutamylated pralatrexate essentially becomes "trapped" inside cancer cells, making it less susceptible to efflux-based drug resistance. Acting on the folate pathway, pralatrexate interferes with DNA synthesis and triggers cancer cell death.
About Pralatrexate in the Treatment of Non-Small Cell Lung Cancer
Two prior clinical studies of pralatrexate in NSCLC formed the basis of the ongoing randomized Phase 2b study. An open-label, single-agent Phase 2 study of pralatrexate in patients with relapsed or refractory Stage IIIB or IV NSCLC at a dose of 135-150 mg/m2 demonstrated a response rate of 11%, a median time to progression of three months and a median survival time of 13.5 months. The most common grade 3 or 4 adverse event was stomatitis, which occurred in 21% of the patients. As a result of subsequent research that suggested supplementation of pralatrexate with folic acid and vitamin B12 may reduce the incidence of clinically significant stomatitis, the Company initiated a Phase 1 dose escalation study of pralatrexate with vitamin B12 and folic acid supplementation in patients with previously treated Stage IIIB/IV advanced NSCLC. In addition to establishing the dosing regimen for the current randomized Phase 2b study, clinically significant radiologic responses were observed.
About Lung Cancer
According to the American Cancer Society, lung cancer is the most common cause of cancer death among men and women in the United States. Approximately 159,390 Americans are expected to die from the disease in 2009 and an estimated 219,440 new cases of lung cancer will be diagnosed this year. Non-small cell lung cancer is the most common type of lung cancer, accounting for almost 80 percent of lung cancer cases. More people die of lung cancer than of breast, prostate and colorectal cancers combined.
Source
Allos Therapeutics, Inc.
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