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Randomized Phase II Trial of a Toll-Like Receptor 9 Agonist Oligodeoxynucleotide, PF-3512676, in Combination With First-Line Taxane Plus Platinum Chemotherapy for Advanced-Stage Non–Small-Cell Lung Cancer

Christian Manegold, Donald Gravenor, Donald Woytowitz, Jörg Mezger, Vera Hirsh, Gary Albert, Mohammed Al-Adhami, David Readett, Arthur M. Krieg, Cynthia Gail Leichman

From the Thorax Klinik Heidelberg, Heidelberg; St Vincentius-Kliniken, Karlsruhe, Germany; Family Cancer Center, Memphis, TN; Florida Cancer Specialists, Fort Myers, FL; Coley Pharmaceutical Group, Inc, Wellesley, MA; Pfizer Inc, Global Research and Development, New London, CT; Comprehensive Cancer Center, Desert Regional Medical Center, Aptium Oncology, Palm Springs, CA; and McGill University, Montreal, Quebec, Canada

Corresponding author: Christian Manegold, MD, University Medical Center Mannheim, Heidelberg University, Mannheim, Germany 68167; e-mail: Prof.Manegold{at}t-online.de

Purpose This study assessed the efficacy of the combination of standard taxane plus platinum chemotherapy with the synthetic Toll-like receptor 9–activating oligodeoxynucleotide PF-3512676 in patients with non–small-cell lung cancer (NSCLC).

Patients and Methods Chemotherapy-naive patients with stage IIIB to IV NSCLC were randomly assigned (one to two ratio) to receive four to six cycles of taxane/platinum chemotherapy alone or with 0.2 mg/kg of subcutaneous PF-3512676 on days 8 and 15 of each 3-week cycle. The primary end point was objective response rate (ORR).

Results Baseline demographics were similar between treatment arms, although significantly more patients in the PF-3512676 arm had stage IV disease (85% compared with 62% in the chemotherapy-alone arm). The modified intent-to-treat analysis (n = 111) demonstrated a 38% ORR (confirmed and unconfirmed) in the PF-3512676 arm (n = 74) and 19% in the chemotherapy-alone arm (n = 37) by investigator evaluation. Blinded, independent radiologic review for 90 patients showed a similar trend in confirmed response rate (19% and 11%, respectively). Median survival was 12.3 months in the PF-3512676 arm and 6.8 months in the chemotherapy-alone arm, and 1-year survival was 50% and 33%, respectively. Mild to moderate local injection site reactions and flu-like symptoms were the most common PF-3512676–related adverse events, but grade 3/4 neutropenia, thrombocytopenia, and anemia were all reported more commonly for patients in the PF-3512676 arm.

Conclusion The addition of PF-3512676 to taxane plus platinum chemotherapy for first-line treatment of NSCLC improves objective response and may improve survival. Confirmatory phase III trials are ongoing.

Supported by Coley Pharmaceutical Group, Inc, and Pfizer Pharmaceuticals Inc (financial support for medical editorial assistance).

Presented in part at the 40th Annual Meeting of the American Society of Clinical Oncology, June 5-8, 2004, New Orleans, LA; Keystone Symposium, Dendritic Cells as the Center of Innate and Adaptive Immunity, February 1-7, 2005, Vancouver, British Columbia, Canada; 41st Annual Meeting of the American Society of Clinical Oncology, May 13-17, 2005, Orlando, FL; European Society for Medical Oncology Scientific and Educational Conference, June 2-5, 2005, Budapest, Hungary; World Conference on Lung Cancer, July 3-6, 2005, Barcelona, Spain; Oligonucleotide Therapeutic Society Annual Meeting, September 15-18, 2005, New York, NY; ECCO 13—the European Cancer Conference, October 31-November 3, 2005, Paris, France; and Second Latin American Conference on Lung Cancer, April 26-28, 2006, Cancun, Mexico.

Authors’ disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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