title: A phase II, multicenter trial of rindopepimut (CDX-110) in newly diagnosed glioblastoma: the ACT III study.
abstract: BACKGROUND
  The epidermal growth factor receptor variant III deletion mutation, EGFRvIII, is expressed in ∼30% of primary glioblastoma and linked to poor long-term survival. Rindopepimut consists of the unique EGFRvIII peptide sequence conjugated to keyhole limpet hemocyanin. In previous phase II trials (ACTIVATE/ACT II), rindopepimut was well tolerated with robust EGFRvIII-specific immune responses and promising progression-free and overall survival. This multicenter, single-arm phase II clinical trial (ACT III) was performed to confirm these results.
  
  
  METHODS
  Rindopepimut and standard adjuvant temozolomide chemotherapy were administered to 65 patients with newly diagnosed EGFRvIII-expressing (EGFRvIII+) glioblastoma after gross total resection and chemoradiation.
  
  
  RESULTS
  Progression-free survival at 5.5 months (∼8.5 mo from diagnosis) was 66%. Relative to study entry, median overall survival was 21.8 months, and 36-month overall survival was 26%. Extended rindopepimut vaccination (up to 3.5+ years) was well tolerated. Grades 1-2 injection site reactions were frequent. Anti-EGFRvIII antibody titers increased ≥4-fold in 85% of patients, and increased with duration of treatment. EGFRvIII was eliminated in 4/6 (67%) tumor samples obtained after >3 months of therapy.
  
  
  CONCLUSIONS
  This study confirms, in a multicenter setting, the preliminary results seen in previous phase II trials of rindopepimut. A pivotal, double-blind, randomized, phase III trial ("ACT IV") is under way.
authors.affiliation: Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania (J.S.); The Neurological Institute of Columbia University, New York, New York (R.K.L.); Stanford Cancer Center, Stanford, California (L.D.R.); Duke University Medical Center, Durham, North Carolina (D.A.R., G.E.A., D.D.B., J.H.S.); Evanston Northwestern Healthcare, Evanston, Illinois (N.A.P.); University of Texas M.D. Anderson Cancer Center, Houston, Texas (M.D.G.); University of Washington School of Medicine, Seattle, Washington (M.M.M.); Huntsman Cancer Institute at the University of Utah, Salt Lake City, Utah (R.J.); Yale University School of Medicine, New Haven, Connecticut (J.M.B); University Hospital-Case Medical Center & Case Comprehensive Cancer Center, Cleveland, Ohio (A.S.); Scott Cruickshank & Associates, Inc., Santa Barbara, C alifornia (S.C.); Celldex Therapeutics, Inc., Hampton, New Jersey (J.A.G., T.K., T.A.D.); University of Texas M.D. Anderson Cancer Center, Houston, Texas (A.B.H.).
authors.forename: James
authors.initials: J
authors.lastname: Schuster
authors.affiliation: Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania (J.S.); The Neurological Institute of Columbia University, New York, New York (R.K.L.); Stanford Cancer Center, Stanford, California (L.D.R.); Duke University Medical Center, Durham, North Carolina (D.A.R., G.E.A., D.D.B., J.H.S.); Evanston Northwestern Healthcare, Evanston, Illinois (N.A.P.); University of Texas M.D. Anderson Cancer Center, Houston, Texas (M.D.G.); University of Washington School of Medicine, Seattle, Washington (M.M.M.); Huntsman Cancer Institute at the University of Utah, Salt Lake City, Utah (R.J.); Yale University School of Medicine, New Haven, Connecticut (J.M.B); University Hospital-Case Medical Center & Case Comprehensive Cancer Center, Cleveland, Ohio (A.S.); Scott Cruickshank & Associates, Inc., Santa Barbara, C alifornia (S.C.); Celldex Therapeutics, Inc., Hampton, New Jersey (J.A.G., T.K., T.A.D.); University of Texas M.D. Anderson Cancer Center, Houston, Texas (A.B.H.).
authors.forename: Rose K
authors.initials: RK
authors.lastname: Lai
authors.affiliation: Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania (J.S.); The Neurological Institute of Columbia University, New York, New York (R.K.L.); Stanford Cancer Center, Stanford, California (L.D.R.); Duke University Medical Center, Durham, North Carolina (D.A.R., G.E.A., D.D.B., J.H.S.); Evanston Northwestern Healthcare, Evanston, Illinois (N.A.P.); University of Texas M.D. Anderson Cancer Center, Houston, Texas (M.D.G.); University of Washington School of Medicine, Seattle, Washington (M.M.M.); Huntsman Cancer Institute at the University of Utah, Salt Lake City, Utah (R.J.); Yale University School of Medicine, New Haven, Connecticut (J.M.B); University Hospital-Case Medical Center & Case Comprehensive Cancer Center, Cleveland, Ohio (A.S.); Scott Cruickshank & Associates, Inc., Santa Barbara, C alifornia (S.C.); Celldex Therapeutics, Inc., Hampton, New Jersey (J.A.G., T.K., T.A.D.); University of Texas M.D. Anderson Cancer Center, Houston, Texas (A.B.H.).
authors.forename: Lawrence D
authors.initials: LD
authors.lastname: Recht
authors.affiliation: Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania (J.S.); The Neurological Institute of Columbia University, New York, New York (R.K.L.); Stanford Cancer Center, Stanford, California (L.D.R.); Duke University Medical Center, Durham, North Carolina (D.A.R., G.E.A., D.D.B., J.H.S.); Evanston Northwestern Healthcare, Evanston, Illinois (N.A.P.); University of Texas M.D. Anderson Cancer Center, Houston, Texas (M.D.G.); University of Washington School of Medicine, Seattle, Washington (M.M.M.); Huntsman Cancer Institute at the University of Utah, Salt Lake City, Utah (R.J.); Yale University School of Medicine, New Haven, Connecticut (J.M.B); University Hospital-Case Medical Center & Case Comprehensive Cancer Center, Cleveland, Ohio (A.S.); Scott Cruickshank & Associates, Inc., Santa Barbara, C alifornia (S.C.); Celldex Therapeutics, Inc., Hampton, New Jersey (J.A.G., T.K., T.A.D.); University of Texas M.D. Anderson Cancer Center, Houston, Texas (A.B.H.).
authors.forename: David A
authors.initials: DA
authors.lastname: Reardon
authors.affiliation: Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania (J.S.); The Neurological Institute of Columbia University, New York, New York (R.K.L.); Stanford Cancer Center, Stanford, California (L.D.R.); Duke University Medical Center, Durham, North Carolina (D.A.R., G.E.A., D.D.B., J.H.S.); Evanston Northwestern Healthcare, Evanston, Illinois (N.A.P.); University of Texas M.D. Anderson Cancer Center, Houston, Texas (M.D.G.); University of Washington School of Medicine, Seattle, Washington (M.M.M.); Huntsman Cancer Institute at the University of Utah, Salt Lake City, Utah (R.J.); Yale University School of Medicine, New Haven, Connecticut (J.M.B); University Hospital-Case Medical Center & Case Comprehensive Cancer Center, Cleveland, Ohio (A.S.); Scott Cruickshank & Associates, Inc., Santa Barbara, C alifornia (S.C.); Celldex Therapeutics, Inc., Hampton, New Jersey (J.A.G., T.K., T.A.D.); University of Texas M.D. Anderson Cancer Center, Houston, Texas (A.B.H.).
authors.forename: Nina A
authors.initials: NA
authors.lastname: Paleologos
authors.affiliation: Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania (J.S.); The Neurological Institute of Columbia University, New York, New York (R.K.L.); Stanford Cancer Center, Stanford, California (L.D.R.); Duke University Medical Center, Durham, North Carolina (D.A.R., G.E.A., D.D.B., J.H.S.); Evanston Northwestern Healthcare, Evanston, Illinois (N.A.P.); University of Texas M.D. Anderson Cancer Center, Houston, Texas (M.D.G.); University of Washington School of Medicine, Seattle, Washington (M.M.M.); Huntsman Cancer Institute at the University of Utah, Salt Lake City, Utah (R.J.); Yale University School of Medicine, New Haven, Connecticut (J.M.B); University Hospital-Case Medical Center & Case Comprehensive Cancer Center, Cleveland, Ohio (A.S.); Scott Cruickshank & Associates, Inc., Santa Barbara, C alifornia (S.C.); Celldex Therapeutics, Inc., Hampton, New Jersey (J.A.G., T.K., T.A.D.); University of Texas M.D. Anderson Cancer Center, Houston, Texas (A.B.H.).
authors.forename: Morris D
authors.initials: MD
authors.lastname: Groves
authors.affiliation: Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania (J.S.); The Neurological Institute of Columbia University, New York, New York (R.K.L.); Stanford Cancer Center, Stanford, California (L.D.R.); Duke University Medical Center, Durham, North Carolina (D.A.R., G.E.A., D.D.B., J.H.S.); Evanston Northwestern Healthcare, Evanston, Illinois (N.A.P.); University of Texas M.D. Anderson Cancer Center, Houston, Texas (M.D.G.); University of Washington School of Medicine, Seattle, Washington (M.M.M.); Huntsman Cancer Institute at the University of Utah, Salt Lake City, Utah (R.J.); Yale University School of Medicine, New Haven, Connecticut (J.M.B); University Hospital-Case Medical Center & Case Comprehensive Cancer Center, Cleveland, Ohio (A.S.); Scott Cruickshank & Associates, Inc., Santa Barbara, C alifornia (S.C.); Celldex Therapeutics, Inc., Hampton, New Jersey (J.A.G., T.K., T.A.D.); University of Texas M.D. Anderson Cancer Center, Houston, Texas (A.B.H.).
authors.forename: Maciej M
authors.initials: MM
authors.lastname: Mrugala
authors.affiliation: Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania (J.S.); The Neurological Institute of Columbia University, New York, New York (R.K.L.); Stanford Cancer Center, Stanford, California (L.D.R.); Duke University Medical Center, Durham, North Carolina (D.A.R., G.E.A., D.D.B., J.H.S.); Evanston Northwestern Healthcare, Evanston, Illinois (N.A.P.); University of Texas M.D. Anderson Cancer Center, Houston, Texas (M.D.G.); University of Washington School of Medicine, Seattle, Washington (M.M.M.); Huntsman Cancer Institute at the University of Utah, Salt Lake City, Utah (R.J.); Yale University School of Medicine, New Haven, Connecticut (J.M.B); University Hospital-Case Medical Center & Case Comprehensive Cancer Center, Cleveland, Ohio (A.S.); Scott Cruickshank & Associates, Inc., Santa Barbara, C alifornia (S.C.); Celldex Therapeutics, Inc., Hampton, New Jersey (J.A.G., T.K., T.A.D.); University of Texas M.D. Anderson Cancer Center, Houston, Texas (A.B.H.).
authors.forename: Randy
authors.initials: R
authors.lastname: Jensen
authors.affiliation: Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania (J.S.); The Neurological Institute of Columbia University, New York, New York (R.K.L.); Stanford Cancer Center, Stanford, California (L.D.R.); Duke University Medical Center, Durham, North Carolina (D.A.R., G.E.A., D.D.B., J.H.S.); Evanston Northwestern Healthcare, Evanston, Illinois (N.A.P.); University of Texas M.D. Anderson Cancer Center, Houston, Texas (M.D.G.); University of Washington School of Medicine, Seattle, Washington (M.M.M.); Huntsman Cancer Institute at the University of Utah, Salt Lake City, Utah (R.J.); Yale University School of Medicine, New Haven, Connecticut (J.M.B); University Hospital-Case Medical Center & Case Comprehensive Cancer Center, Cleveland, Ohio (A.S.); Scott Cruickshank & Associates, Inc., Santa Barbara, C alifornia (S.C.); Celldex Therapeutics, Inc., Hampton, New Jersey (J.A.G., T.K., T.A.D.); University of Texas M.D. Anderson Cancer Center, Houston, Texas (A.B.H.).
authors.forename: Joachim M
authors.initials: JM
authors.lastname: Baehring
authors.affiliation: Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania (J.S.); The Neurological Institute of Columbia University, New York, New York (R.K.L.); Stanford Cancer Center, Stanford, California (L.D.R.); Duke University Medical Center, Durham, North Carolina (D.A.R., G.E.A., D.D.B., J.H.S.); Evanston Northwestern Healthcare, Evanston, Illinois (N.A.P.); University of Texas M.D. Anderson Cancer Center, Houston, Texas (M.D.G.); University of Washington School of Medicine, Seattle, Washington (M.M.M.); Huntsman Cancer Institute at the University of Utah, Salt Lake City, Utah (R.J.); Yale University School of Medicine, New Haven, Connecticut (J.M.B); University Hospital-Case Medical Center & Case Comprehensive Cancer Center, Cleveland, Ohio (A.S.); Scott Cruickshank & Associates, Inc., Santa Barbara, C alifornia (S.C.); Celldex Therapeutics, Inc., Hampton, New Jersey (J.A.G., T.K., T.A.D.); University of Texas M.D. Anderson Cancer Center, Houston, Texas (A.B.H.).
authors.forename: Andrew
authors.initials: A
authors.lastname: Sloan
authors.affiliation: Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania (J.S.); The Neurological Institute of Columbia University, New York, New York (R.K.L.); Stanford Cancer Center, Stanford, California (L.D.R.); Duke University Medical Center, Durham, North Carolina (D.A.R., G.E.A., D.D.B., J.H.S.); Evanston Northwestern Healthcare, Evanston, Illinois (N.A.P.); University of Texas M.D. Anderson Cancer Center, Houston, Texas (M.D.G.); University of Washington School of Medicine, Seattle, Washington (M.M.M.); Huntsman Cancer Institute at the University of Utah, Salt Lake City, Utah (R.J.); Yale University School of Medicine, New Haven, Connecticut (J.M.B); University Hospital-Case Medical Center & Case Comprehensive Cancer Center, Cleveland, Ohio (A.S.); Scott Cruickshank & Associates, Inc., Santa Barbara, C alifornia (S.C.); Celldex Therapeutics, Inc., Hampton, New Jersey (J.A.G., T.K., T.A.D.); University of Texas M.D. Anderson Cancer Center, Houston, Texas (A.B.H.).
authors.forename: Gary E
authors.initials: GE
authors.lastname: Archer
authors.affiliation: Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania (J.S.); The Neurological Institute of Columbia University, New York, New York (R.K.L.); Stanford Cancer Center, Stanford, California (L.D.R.); Duke University Medical Center, Durham, North Carolina (D.A.R., G.E.A., D.D.B., J.H.S.); Evanston Northwestern Healthcare, Evanston, Illinois (N.A.P.); University of Texas M.D. Anderson Cancer Center, Houston, Texas (M.D.G.); University of Washington School of Medicine, Seattle, Washington (M.M.M.); Huntsman Cancer Institute at the University of Utah, Salt Lake City, Utah (R.J.); Yale University School of Medicine, New Haven, Connecticut (J.M.B); University Hospital-Case Medical Center & Case Comprehensive Cancer Center, Cleveland, Ohio (A.S.); Scott Cruickshank & Associates, Inc., Santa Barbara, C alifornia (S.C.); Celldex Therapeutics, Inc., Hampton, New Jersey (J.A.G., T.K., T.A.D.); University of Texas M.D. Anderson Cancer Center, Houston, Texas (A.B.H.).
authors.forename: Darell D
authors.initials: DD
authors.lastname: Bigner
authors.affiliation: Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania (J.S.); The Neurological Institute of Columbia University, New York, New York (R.K.L.); Stanford Cancer Center, Stanford, California (L.D.R.); Duke University Medical Center, Durham, North Carolina (D.A.R., G.E.A., D.D.B., J.H.S.); Evanston Northwestern Healthcare, Evanston, Illinois (N.A.P.); University of Texas M.D. Anderson Cancer Center, Houston, Texas (M.D.G.); University of Washington School of Medicine, Seattle, Washington (M.M.M.); Huntsman Cancer Institute at the University of Utah, Salt Lake City, Utah (R.J.); Yale University School of Medicine, New Haven, Connecticut (J.M.B); University Hospital-Case Medical Center & Case Comprehensive Cancer Center, Cleveland, Ohio (A.S.); Scott Cruickshank & Associates, Inc., Santa Barbara, C alifornia (S.C.); Celldex Therapeutics, Inc., Hampton, New Jersey (J.A.G., T.K., T.A.D.); University of Texas M.D. Anderson Cancer Center, Houston, Texas (A.B.H.).
authors.forename: Scott
authors.initials: S
authors.lastname: Cruickshank
authors.affiliation: Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania (J.S.); The Neurological Institute of Columbia University, New York, New York (R.K.L.); Stanford Cancer Center, Stanford, California (L.D.R.); Duke University Medical Center, Durham, North Carolina (D.A.R., G.E.A., D.D.B., J.H.S.); Evanston Northwestern Healthcare, Evanston, Illinois (N.A.P.); University of Texas M.D. Anderson Cancer Center, Houston, Texas (M.D.G.); University of Washington School of Medicine, Seattle, Washington (M.M.M.); Huntsman Cancer Institute at the University of Utah, Salt Lake City, Utah (R.J.); Yale University School of Medicine, New Haven, Connecticut (J.M.B); University Hospital-Case Medical Center & Case Comprehensive Cancer Center, Cleveland, Ohio (A.S.); Scott Cruickshank & Associates, Inc., Santa Barbara, C alifornia (S.C.); Celldex Therapeutics, Inc., Hampton, New Jersey (J.A.G., T.K., T.A.D.); University of Texas M.D. Anderson Cancer Center, Houston, Texas (A.B.H.).
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Green
authors.affiliation: Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania (J.S.); The Neurological Institute of Columbia University, New York, New York (R.K.L.); Stanford Cancer Center, Stanford, California (L.D.R.); Duke University Medical Center, Durham, North Carolina (D.A.R., G.E.A., D.D.B., J.H.S.); Evanston Northwestern Healthcare, Evanston, Illinois (N.A.P.); University of Texas M.D. Anderson Cancer Center, Houston, Texas (M.D.G.); University of Washington School of Medicine, Seattle, Washington (M.M.M.); Huntsman Cancer Institute at the University of Utah, Salt Lake City, Utah (R.J.); Yale University School of Medicine, New Haven, Connecticut (J.M.B); University Hospital-Case Medical Center & Case Comprehensive Cancer Center, Cleveland, Ohio (A.S.); Scott Cruickshank & Associates, Inc., Santa Barbara, C alifornia (S.C.); Celldex Therapeutics, Inc., Hampton, New Jersey (J.A.G., T.K., T.A.D.); University of Texas M.D. Anderson Cancer Center, Houston, Texas (A.B.H.).
authors.forename: Tibor
authors.initials: T
authors.lastname: Keler
authors.affiliation: Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania (J.S.); The Neurological Institute of Columbia University, New York, New York (R.K.L.); Stanford Cancer Center, Stanford, California (L.D.R.); Duke University Medical Center, Durham, North Carolina (D.A.R., G.E.A., D.D.B., J.H.S.); Evanston Northwestern Healthcare, Evanston, Illinois (N.A.P.); University of Texas M.D. Anderson Cancer Center, Houston, Texas (M.D.G.); University of Washington School of Medicine, Seattle, Washington (M.M.M.); Huntsman Cancer Institute at the University of Utah, Salt Lake City, Utah (R.J.); Yale University School of Medicine, New Haven, Connecticut (J.M.B); University Hospital-Case Medical Center & Case Comprehensive Cancer Center, Cleveland, Ohio (A.S.); Scott Cruickshank & Associates, Inc., Santa Barbara, C alifornia (S.C.); Celldex Therapeutics, Inc., Hampton, New Jersey (J.A.G., T.K., T.A.D.); University of Texas M.D. Anderson Cancer Center, Houston, Texas (A.B.H.).
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Davis
authors.affiliation: Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania (J.S.); The Neurological Institute of Columbia University, New York, New York (R.K.L.); Stanford Cancer Center, Stanford, California (L.D.R.); Duke University Medical Center, Durham, North Carolina (D.A.R., G.E.A., D.D.B., J.H.S.); Evanston Northwestern Healthcare, Evanston, Illinois (N.A.P.); University of Texas M.D. Anderson Cancer Center, Houston, Texas (M.D.G.); University of Washington School of Medicine, Seattle, Washington (M.M.M.); Huntsman Cancer Institute at the University of Utah, Salt Lake City, Utah (R.J.); Yale University School of Medicine, New Haven, Connecticut (J.M.B); University Hospital-Case Medical Center & Case Comprehensive Cancer Center, Cleveland, Ohio (A.S.); Scott Cruickshank & Associates, Inc., Santa Barbara, C alifornia (S.C.); Celldex Therapeutics, Inc., Hampton, New Jersey (J.A.G., T.K., T.A.D.); University of Texas M.D. Anderson Cancer Center, Houston, Texas (A.B.H.).
authors.forename: Amy B
authors.initials: AB
authors.lastname: Heimberger
authors.affiliation: Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania (J.S.); The Neurological Institute of Columbia University, New York, New York (R.K.L.); Stanford Cancer Center, Stanford, California (L.D.R.); Duke University Medical Center, Durham, North Carolina (D.A.R., G.E.A., D.D.B., J.H.S.); Evanston Northwestern Healthcare, Evanston, Illinois (N.A.P.); University of Texas M.D. Anderson Cancer Center, Houston, Texas (M.D.G.); University of Washington School of Medicine, Seattle, Washington (M.M.M.); Huntsman Cancer Institute at the University of Utah, Salt Lake City, Utah (R.J.); Yale University School of Medicine, New Haven, Connecticut (J.M.B); University Hospital-Case Medical Center & Case Comprehensive Cancer Center, Cleveland, Ohio (A.S.); Scott Cruickshank & Associates, Inc., Santa Barbara, C alifornia (S.C.); Celldex Therapeutics, Inc., Hampton, New Jersey (J.A.G., T.K., T.A.D.); University of Texas M.D. Anderson Cancer Center, Houston, Texas (A.B.H.).
authors.forename: John H
authors.initials: JH
authors.lastname: Sampson
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000532:radiotherapy; D019496:Cancer Vaccines / Q000627:therapeutic use*; D059186:Chemoradiotherapy, Adjuvant; D003606:Dacarbazine / Q000031:analogs & derivatives / Q000627:therapeutic use; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000235:genetics; D005260:Female; D005909:Glioblastoma / Q000188:drug therapy* / Q000401:mortality / Q000532:radiotherapy; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D000077204:Temozolomide; D016896:Treatment Outcome; D022223:Vaccines, Subunit / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; D019496:Cancer Vaccines; D022223:Vaccines, Subunit; C410723:epidermal growth factor receptor VIII; D003606:Dacarbazine; D066246:ErbB Receptors; C558237:rindopepimut; D000077204:Temozolomide
keywords: ACT III; EGFRvIII; glioblastoma; glioma; rindopepimut