A randomized, double-blind, placebo-controlled phase 2 trial of dendritic cell (DC) vaccination with ICT-107 in newly diagnosed glioblastoma (GBM) patients.

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Journal: J Clin Oncol 32:5s, 2014 (suppl; abstr 2005)

Authors:
Patrick Y. Wen, David A. Reardon, Surasak Phuphanich, Robert Aiken, Joseph C. Landolfi, William T. Curry, Jay-Jiguang Zhu, Michael J. Glantz, David M. Peereboom, James Markert, Renato V. LaRocca, Donald O’Rourke, Karen L. Fink, Lyndon J. Kim, Michael L. Gruber, Glenn Jay Lesser, Edward Pan, Santosh Kesari, Elma S. Hawkins, John Yu; Dana-Farber Cancer Institute, Boston, MA; Dana-Farber Cancer Center Institute, Boston, MA; Neuro-Oncology Program, Cedars-Sinai Medical Center, Los Angeles, CA; Rush University, Chicago, IL; New Jersey Neuroscience Institute at JFK Medical Center, Edison, NJ; Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA; The University of Texas Health Science Center at Houston, Houston, TX; Penn State Milton S. Hershey Medical Center, Hershey, PA; Cleveland Clinic, Cleveland, OH; The University of Alabama at Birmingham Comprehensive Cancer Center, Birmingham, AL; Kentuckiana Cancer Inst PLLC, Louisville, KY; University of Pennsylvania, Philadelphia, PA; Baylor Research Institute, Dallas, TX; Thomas Jefferson University, Philadelphia, PA; New York University Langone Medical Center, New York, NY; Wake Forest University, School of Medicine, Winston-Salem, NC; H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL; University of California, San Diego, La Jolla, CA; Immunocellular Therapeutics, Calabasas, CA

ABSTRACT

Background: The trial investigated whether adding tumor-antigen-loaded DC vaccine to surgery and chemoradiation would improve overall survival (OS) or progression free survival (PFS).

Methods: HLA-A1+ and/or -A2+ resected patients with residual tumor <1 cm3 received 6 weeks of concurrent temozolomide (TMZ) and radiation. 124 patients were randomized 2:1 to receive ICT-107 (autologous PBMC-derived DC pulsed with 6 synthetic peptide CTL epitopes targeting the GBM tumor and tumor stem cell-associated antigens MAGE-1, HER-2, AIM-2, TRP-2, gp100, and IL-13Rα2) or its matching control (unpulsed DC). Patients then received induction ICT-107 or control QWx4 followed by maintenance TMZ, 5 days/mo for 12 mos. Booster vaccinations occurred at 1, 3, and 6 mos after induction, and every 6 mos thereafter. The trial concluded and data were evaluated at 67 events.

Results: ICT-107 was generally safe and well tolerated, with no imbalance in AEs between the treated and control groups. PFS improved by 2 mos in the ICT-107 ITT group (p=0.02 two-sided, hazard ratio (HR)=0.56). In the per-protocol (PP) group (117 patients receiving all 4 induction vaccinations), p=0.01 two-sided, HR=0.53, and the difference in median PFS increased to 3 mos. The median OS favored ICT-107 by 2 mos in the ITT and 3 mos in the PP groups. However, the number of events was small and OS did not reach statistical significance (p=0.58 two-sided, HR=0.87, and p=0.40 two-sided, HR=0.79, respectively). Median follow-up from randomization was 13.6 mos. In the ICT-107 group, vaccine activation markers IL12 and HLA-DR were predictive of OS (p-values < 0.05). There were no correlations in the placebo group.

Conclusions: This is the first randomized, placebo-controlled immunotherapy trial in GBM to positively affect a clinical outcome, PFS. Although OS improvement was not statistically significant at the 67/124 event point, patients continue to be followed for OS, allowing periodic updating of the primary endpoint and assessment of long-term survival. Analysis of QOL, and correlation of both tumor antigen expression and vaccine immunologic response with OS are in process.

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