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Published on: October 27, 2014
Pembrolizumab, Temozolomide and HSPPC-96 Vaccine in Newly Diagnosed Glioblastoma Post-Chemoradiation: Results from a
Byram H Ozer1, Scott M Lindhorst1, Ryan T Merrell1
1Neuro-Oncology Branch, National Cancer Institute/National Institutes of Health, Bethesda, Maryland, USA (B.H.O., E.B., J.W., H.L., J.G., M.P.-P., Y.Y., C.C., K.W., E.G., T.M., T.S.A., M.R.G.); Department of Neurosurgery, Medical University of South Carolina, Charleston, South Carolina, USA (S.M.L.); Department of Neurology, NorthShore University Health System, Chicago, Illinois, USA (R.T.M., C.R.T.); Department of Neurology, Cedars-Sinai Medical Center, Los Angeles, California, USA (J.D.R.); Department of Hematology and Medical Oncology (N.G.A.) and Department of Radiation Oncology (N.R.), Orlando Regional Medical Center, Orlando, Florida, USA (N.G.A., N.R.); Department of Neurology and Neurosurgery, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA (S.K., Y.R.); Department of Neurology and Neurosurgery, Henry Ford Health System, Detroit, Michigan, USA (T.W.); Department of Neurology, University of Texas Southwestern, Dallas, Texas, USA (E.P., M.Y.); Department of Neurology/Neuro-Oncology, Baylor Scott&White, Baylor University Medical Center, Houston, Texas, USA (K.L.F.); Department of Neurology, Baylor College of Medicine, Houston, Texas, USA (J.J.M.); Department of Neurology, Alvord Brain Tumor Center, University of Washington and Fred Hutchinson Cancer Center, Seattle, Washington, USA (L.P.T.); Department of Neurosurgery, Huntsman Cancer Institute, Salt Lake City, Utah, USA (H.C.); Piedmont Brain Tumor Center, Atlanta, Georgia, USA (E.M.D.); Division of Neurology, Advocate Medical Group, Downers Grove, Illinois, USA (N.P.); Department of Neurology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois (J.J.R.); Department of Biostatistics, MD Anderson Cancer Center, Houston, Texas, USA (Y.Y.); Scientific Leadership and Research Manager, MSD/Merck&Co, Inc., Rahway, New Jersey, USA (E.V.); Director of Manufacturing and Logistics, Agenus, Lexington, Massachusetts, USA (S.C.).
Background:
GBM is one of the most common and most aggressive brain tumors in adults, and upfront standard of care treatment has limited efficacy. Immune checkpoint inhibitor strategies have significantly improved outcomes in various solid tumors but have not proven effective in GBM, suggesting other strategies may be needed to realize their full potential.
Methods:
GBM patients were treated with upfront standard of care chemoradiation with temozolomide and pembrolizumab, followed by adjuvant temozolomide and pembrolizumab for six nine-week cycles. Depending on production of sufficient vaccine, patients were randomized into HSPPC-96 vaccine or placebo group (q4 weeks) while those with failed vaccine production continued on study unblinded as an ancillary group. The primary objective was overall survival at one year, and secondary endpoints were progression-free survival at six months, overall and progression-free survival, radiographic response, and tolerability by patient-reported outcomes and adverse event documentation.
Results:
90 patients were screened, 32 were treated (8 vaccine, 9 placebo, 15 ancillary), and 26 were evaluable for radiographic responses prior to accrual termination. The study did not meet its primary endpoint of overall survival at one year (65.5% in vaccine group, 75% in placebo). Progression-free endpoints were mildly improved in the vaccine group but were not significant, and response rates were not significantly different. The regimen was well-tolerated and safe.
Conclusions:
Though limited by early discontinuation, these findings do not support the combination of pembrolizumab and HSPPC-96 vaccine with standard of care therapy.
Trials Registration:
ClinicalTrials.gov identifier: NCT03018288.
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