A randomized double-blind placebo-controlled phase II trial of dendritic cell vaccine ICT-107 in newly diagnosed patients with glioblastoma

Patrick Y. Wen, David A. Reardon, Terri S. Armstrong, Surasak Phuphanich, Robert D. Aiken, Joseph C. Landolfi, William T. Curry, Jay Jiguang Zhu, Michael Glantz, David M. Peereboom, James M. Markert, Renato LaRocca, Donald M. O'Rourke, Karen Fink, Lyndon Kim, Michael Gruber, Glenn J. Lesser, Edward Pan, Santosh Kesari, Alona MuzikanskyClemencia Pinilla, Radleigh G. Santos, John S. Yu

Research output: Contribution to journalArticle

Abstract

Purpose: To evaluate the results of the randomized, double-blind, placebo-controlled phase II clinical trial of ICT-107 in patients with newly diagnosed glioblastoma. Patients and Methods: We conducted a double-blinded randomized phase II trial of ICT-107 in newly diagnosed patients with glioblastoma (GBM) and tested efficacy, safety, quality of life (QoL), and immune response. HLA-A1þ and/or -A2þ–resected patients with residual tumor ≤1 cm3 received radiotherapy and concurrent temozolomide. Following completion of radiotherapy, 124 patients, randomized 2:1, received ICT-107 [autologous dendritic cells (DC) pulsed with six synthetic peptide epitopes targeting GBM tumor/stem cell–associated antigens MAGE-1, HER-2, AIM-2, TRP-2, gp100, and IL13Ra2] or matching control (unpulsed DC). Patients received induction ICT-107 or control weekly x 4 followed by 12 months of adjuvant temozolomide. Maintenance vaccinations occurred at 1, 3, and 6 months and every 6 months thereafter. Results: ICT-107 was well tolerated, with no difference in adverse events between the treatment and control groups. The primary endpoint, median overall survival (OS), favored ICT-107 by 2.0 months in the intent-to-treat (ITT) population but was not statistically significant. Progression-free survival (PFS) in the ITT population was significantly increased in the ICT-107 cohort by 2.2 months (P ¼ 0.011). The frequency of HLA-A2 primary tumor antigen expression was higher than that for HLA-A1 patients, and HLA-A2 patients had higher immune response (via Elispot). HLA-A2 patients achieved a meaningful therapeutic benefit with ICT-107, in both the MGMT methylated and unmethylated prespecified subgroups, whereas only HLA-A1 methylated patients had an OS benefit. Conclusions: PFS was significantly improved in ICT-107–treated patients with maintenance of QoL. Patients in the HLA-A2 subgroup showed increased ICT-107 activity clinically and immunologically.

Original languageEnglish (US)
Pages (from-to)5799-5807
Number of pages9
JournalClinical Cancer Research
Volume25
Issue number19
DOIs
StatePublished - Oct 1 2019

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Glioblastoma
Dendritic Cells
Vaccines
Placebos
HLA-A2 Antigen
HLA-A1 Antigen
temozolomide
Disease-Free Survival
Radiotherapy
Maintenance
Quality of Life
Phase II Clinical Trials
Survival
Controlled Clinical Trials
Residual Neoplasm
Neoplasm Antigens
Population
Epitopes
Vaccination
Safety

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Wen, Patrick Y. ; Reardon, David A. ; Armstrong, Terri S. ; Phuphanich, Surasak ; Aiken, Robert D. ; Landolfi, Joseph C. ; Curry, William T. ; Zhu, Jay Jiguang ; Glantz, Michael ; Peereboom, David M. ; Markert, James M. ; LaRocca, Renato ; O'Rourke, Donald M. ; Fink, Karen ; Kim, Lyndon ; Gruber, Michael ; Lesser, Glenn J. ; Pan, Edward ; Kesari, Santosh ; Muzikansky, Alona ; Pinilla, Clemencia ; Santos, Radleigh G. ; Yu, John S. / A randomized double-blind placebo-controlled phase II trial of dendritic cell vaccine ICT-107 in newly diagnosed patients with glioblastoma. In: Clinical Cancer Research. 2019 ; Vol. 25, No. 19. pp. 5799-5807.
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abstract = "Purpose: To evaluate the results of the randomized, double-blind, placebo-controlled phase II clinical trial of ICT-107 in patients with newly diagnosed glioblastoma. Patients and Methods: We conducted a double-blinded randomized phase II trial of ICT-107 in newly diagnosed patients with glioblastoma (GBM) and tested efficacy, safety, quality of life (QoL), and immune response. HLA-A1{\th} and/or -A2{\th}–resected patients with residual tumor ≤1 cm3 received radiotherapy and concurrent temozolomide. Following completion of radiotherapy, 124 patients, randomized 2:1, received ICT-107 [autologous dendritic cells (DC) pulsed with six synthetic peptide epitopes targeting GBM tumor/stem cell–associated antigens MAGE-1, HER-2, AIM-2, TRP-2, gp100, and IL13Ra2] or matching control (unpulsed DC). Patients received induction ICT-107 or control weekly x 4 followed by 12 months of adjuvant temozolomide. Maintenance vaccinations occurred at 1, 3, and 6 months and every 6 months thereafter. Results: ICT-107 was well tolerated, with no difference in adverse events between the treatment and control groups. The primary endpoint, median overall survival (OS), favored ICT-107 by 2.0 months in the intent-to-treat (ITT) population but was not statistically significant. Progression-free survival (PFS) in the ITT population was significantly increased in the ICT-107 cohort by 2.2 months (P ¼ 0.011). The frequency of HLA-A2 primary tumor antigen expression was higher than that for HLA-A1 patients, and HLA-A2 patients had higher immune response (via Elispot). HLA-A2 patients achieved a meaningful therapeutic benefit with ICT-107, in both the MGMT methylated and unmethylated prespecified subgroups, whereas only HLA-A1 methylated patients had an OS benefit. Conclusions: PFS was significantly improved in ICT-107–treated patients with maintenance of QoL. Patients in the HLA-A2 subgroup showed increased ICT-107 activity clinically and immunologically.",
author = "Wen, {Patrick Y.} and Reardon, {David A.} and Armstrong, {Terri S.} and Surasak Phuphanich and Aiken, {Robert D.} and Landolfi, {Joseph C.} and Curry, {William T.} and Zhu, {Jay Jiguang} and Michael Glantz and Peereboom, {David M.} and Markert, {James M.} and Renato LaRocca and O'Rourke, {Donald M.} and Karen Fink and Lyndon Kim and Michael Gruber and Lesser, {Glenn J.} and Edward Pan and Santosh Kesari and Alona Muzikansky and Clemencia Pinilla and Santos, {Radleigh G.} and Yu, {John S.}",
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Wen, PY, Reardon, DA, Armstrong, TS, Phuphanich, S, Aiken, RD, Landolfi, JC, Curry, WT, Zhu, JJ, Glantz, M, Peereboom, DM, Markert, JM, LaRocca, R, O'Rourke, DM, Fink, K, Kim, L, Gruber, M, Lesser, GJ, Pan, E, Kesari, S, Muzikansky, A, Pinilla, C, Santos, RG & Yu, JS 2019, 'A randomized double-blind placebo-controlled phase II trial of dendritic cell vaccine ICT-107 in newly diagnosed patients with glioblastoma', Clinical Cancer Research, vol. 25, no. 19, pp. 5799-5807. https://doi.org/10.1158/1078-0432.CCR-19-0261

A randomized double-blind placebo-controlled phase II trial of dendritic cell vaccine ICT-107 in newly diagnosed patients with glioblastoma. / Wen, Patrick Y.; Reardon, David A.; Armstrong, Terri S.; Phuphanich, Surasak; Aiken, Robert D.; Landolfi, Joseph C.; Curry, William T.; Zhu, Jay Jiguang; Glantz, Michael; Peereboom, David M.; Markert, James M.; LaRocca, Renato; O'Rourke, Donald M.; Fink, Karen; Kim, Lyndon; Gruber, Michael; Lesser, Glenn J.; Pan, Edward; Kesari, Santosh; Muzikansky, Alona; Pinilla, Clemencia; Santos, Radleigh G.; Yu, John S.

In: Clinical Cancer Research, Vol. 25, No. 19, 01.10.2019, p. 5799-5807.

Research output: Contribution to journalArticle

TY - JOUR

T1 - A randomized double-blind placebo-controlled phase II trial of dendritic cell vaccine ICT-107 in newly diagnosed patients with glioblastoma

AU - Wen, Patrick Y.

AU - Reardon, David A.

AU - Armstrong, Terri S.

AU - Phuphanich, Surasak

AU - Aiken, Robert D.

AU - Landolfi, Joseph C.

AU - Curry, William T.

AU - Zhu, Jay Jiguang

AU - Glantz, Michael

AU - Peereboom, David M.

AU - Markert, James M.

AU - LaRocca, Renato

AU - O'Rourke, Donald M.

AU - Fink, Karen

AU - Kim, Lyndon

AU - Gruber, Michael

AU - Lesser, Glenn J.

AU - Pan, Edward

AU - Kesari, Santosh

AU - Muzikansky, Alona

AU - Pinilla, Clemencia

AU - Santos, Radleigh G.

AU - Yu, John S.

PY - 2019/10/1

Y1 - 2019/10/1

N2 - Purpose: To evaluate the results of the randomized, double-blind, placebo-controlled phase II clinical trial of ICT-107 in patients with newly diagnosed glioblastoma. Patients and Methods: We conducted a double-blinded randomized phase II trial of ICT-107 in newly diagnosed patients with glioblastoma (GBM) and tested efficacy, safety, quality of life (QoL), and immune response. HLA-A1þ and/or -A2þ–resected patients with residual tumor ≤1 cm3 received radiotherapy and concurrent temozolomide. Following completion of radiotherapy, 124 patients, randomized 2:1, received ICT-107 [autologous dendritic cells (DC) pulsed with six synthetic peptide epitopes targeting GBM tumor/stem cell–associated antigens MAGE-1, HER-2, AIM-2, TRP-2, gp100, and IL13Ra2] or matching control (unpulsed DC). Patients received induction ICT-107 or control weekly x 4 followed by 12 months of adjuvant temozolomide. Maintenance vaccinations occurred at 1, 3, and 6 months and every 6 months thereafter. Results: ICT-107 was well tolerated, with no difference in adverse events between the treatment and control groups. The primary endpoint, median overall survival (OS), favored ICT-107 by 2.0 months in the intent-to-treat (ITT) population but was not statistically significant. Progression-free survival (PFS) in the ITT population was significantly increased in the ICT-107 cohort by 2.2 months (P ¼ 0.011). The frequency of HLA-A2 primary tumor antigen expression was higher than that for HLA-A1 patients, and HLA-A2 patients had higher immune response (via Elispot). HLA-A2 patients achieved a meaningful therapeutic benefit with ICT-107, in both the MGMT methylated and unmethylated prespecified subgroups, whereas only HLA-A1 methylated patients had an OS benefit. Conclusions: PFS was significantly improved in ICT-107–treated patients with maintenance of QoL. Patients in the HLA-A2 subgroup showed increased ICT-107 activity clinically and immunologically.

AB - Purpose: To evaluate the results of the randomized, double-blind, placebo-controlled phase II clinical trial of ICT-107 in patients with newly diagnosed glioblastoma. Patients and Methods: We conducted a double-blinded randomized phase II trial of ICT-107 in newly diagnosed patients with glioblastoma (GBM) and tested efficacy, safety, quality of life (QoL), and immune response. HLA-A1þ and/or -A2þ–resected patients with residual tumor ≤1 cm3 received radiotherapy and concurrent temozolomide. Following completion of radiotherapy, 124 patients, randomized 2:1, received ICT-107 [autologous dendritic cells (DC) pulsed with six synthetic peptide epitopes targeting GBM tumor/stem cell–associated antigens MAGE-1, HER-2, AIM-2, TRP-2, gp100, and IL13Ra2] or matching control (unpulsed DC). Patients received induction ICT-107 or control weekly x 4 followed by 12 months of adjuvant temozolomide. Maintenance vaccinations occurred at 1, 3, and 6 months and every 6 months thereafter. Results: ICT-107 was well tolerated, with no difference in adverse events between the treatment and control groups. The primary endpoint, median overall survival (OS), favored ICT-107 by 2.0 months in the intent-to-treat (ITT) population but was not statistically significant. Progression-free survival (PFS) in the ITT population was significantly increased in the ICT-107 cohort by 2.2 months (P ¼ 0.011). The frequency of HLA-A2 primary tumor antigen expression was higher than that for HLA-A1 patients, and HLA-A2 patients had higher immune response (via Elispot). HLA-A2 patients achieved a meaningful therapeutic benefit with ICT-107, in both the MGMT methylated and unmethylated prespecified subgroups, whereas only HLA-A1 methylated patients had an OS benefit. Conclusions: PFS was significantly improved in ICT-107–treated patients with maintenance of QoL. Patients in the HLA-A2 subgroup showed increased ICT-107 activity clinically and immunologically.

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