TY - JOUR
T1 - Rindopepimut with bevacizumab for patients with relapsed EGFRvIII-expressing glioblastoma (REACT)
T2 - Results of a double-blind randomized phase II trial
AU - for the ReACT trial investigators
AU - Reardon, David A.
AU - Desjardins, Annick
AU - Vredenburgh, James J.
AU - O'Rourke, Donald M.
AU - Tran, David D.
AU - Fink, Karen L.
AU - Nabors, Louis B.
AU - Li, Gordon
AU - Bota, Daniela A.
AU - Lukas, Rimas V.
AU - Ashby, Lynn S.
AU - Paul Duic, J.
AU - Mrugala, Maciej M.
AU - Cruickshank, Scott
AU - Vitale, Laura
AU - He, Yi
AU - Green, Jennifer A.
AU - Yellin, Michael J.
AU - Turner, Christopher D.
AU - Keler, Tibor
AU - Davis, Thomas A.
AU - Sampson, John H.
N1 - Funding Information:
This study was sponsored and funded by Celldex Therapeutics, Inc. The study sponsor designed the study in collaboration with the investigators, managed the clinical trial database, performed statistical analysis, and provided medical writing assistance. The corresponding author had full access to all the data in the study and had final responsibility for the decision to submit for publication.
Funding Information:
D.A. Reardon is a paid consultant for Abbvie, Advantagene, Agenus, Amgen, Bayer, Bristol-Myers Squibb, Celldex, Delmar, EMD Serono, Genentech/Roche, Inovio, Merck, Merck KGaA, Monteris, Novocure, Oncurus, Oxigene, Regeneron, Stemline, and Taiho Oncology. A. Desjardins reports receiving other commercial research support from Genentech/Roche, Triphase Accelerator, Symphogen A/S, Orbus Therapeutics; holds ownership interest (including patents) in Istari Oncology; and is an unpaid consultant/advisory board member for Orbus Therapeutics and Istari Oncology. D.M. O’Rourke reports receiving commercial research grants and other commercial research support from Novartis; holds ownership interest (including patents) in Isoma Therapeutics; and reports receiving other remuneration for providing expert clinical testimony. D.D. Tran is an employee of Novocure and Monteris, and reports receiving commercial research grants from Novocure, Merck, Tocagen, Novartis, Stemline, Northwest Biotech, and Lacerta. K. Fink is an unpaid consultant/advisory board member for UCB Pharma. L.B. Nabors reports receiving other remuneration from BTG and Karyopharm. D.A. Bota is a paid consultant for Tocagen and PCT Pharma and reports receiving speakers bureau honoraria from Novocure and Zailab. R.V. Lukas is a paid consultant for Abbvie, Eisai, and Monteris, and reports receiving other remuneration from EBSCO, Medlink Neurology, American Physician Institute, and Bristol-Myers Squibb. L. Vitale holds ownership interest (including patents) in Celldex Therapeutics. Y. He holds ownership interest (including patents) in Celldex Therapeutics. J.A. Green is an employee of and holds ownership interest (including patents) in Celldex. M.J. Yellin is an employee of and holds ownership interest (including patents) in Celldex. C.D. Turner is an employee of and holds ownership interest (including patents) in Celldex. T. Keler is an employee of and holds ownership interest (including patents) in Celldex. T.A. Davis is an employee of and holds ownership interest (including patents) in Celldex. J.H. Sampson is a paid consultant for Bristol-Myers Squibb and holds ownership interest (including patents) in Istari Oncology and Annias Therapeutics. No potential conflicts of interest were disclosed by the other authors.
Funding Information:
We thank the study patients and their families, all the participating investigators and research staff, and the expert review committee members John deGroot, MD, Raymond Y. Huang, MD, PhD, and Whitney Pope, MD, PhD. An earlier version of this manuscript was prepared with medical writing assistance provided by Mark Calcamuggio (the Write Company). This study was sponsored and funded by Celldex Therapeutics, Inc.
PY - 2020/4/1
Y1 - 2020/4/1
N2 - Purpose: Rindopepimut is a vaccine targeting the tumor-specific EGF driver mutation, EGFRvIII. The ReACT study investigated whether the addition of rindopepimut to standard bevacizumab improved outcome for patients with relapsed, EGFRvIII-positive glioblastoma. Patients and Methods: In this double-blind, randomized, phase II study (NCT01498328) conducted at 26 hospitals in the United States, bevacizumab-native patients with recurrent EGFRvIII-positive glioblastoma were randomized to receive rindopepimut or a control injection of keyhole limpet hemocyanin, each concurrent with bevacizumab. The primary endpoint was 6-month progression-free survival (PFS6) by central review with a one-sided significance of 0.2. Results: Between May 2012 and 2014, 73 patients were randomized (36 rindopepimut, 37 control). Rindopepimut toxicity included transient, low-grade local reactions. As primary endpoint, PFS6 was 28% (10/36) for rindopepimut compared with 16% (6/37) for control (P ¼ 0.12, one-sided). Secondary and exploratory endpoints also favored the rindopepimut group including a statistically significant survival advantage [HR, 0.53; 95% confidence interval (CI), 0.32-0.88; two-sided log-rank P ¼ 0.01], a higher ORR [30% (9/30) vs. 18% (6/34; P ¼ 0.38)], median duration of response [7.8 months (95% CI, 3.5-22.2) vs. 5.6 (95% CI, 3.7-7.4)], and ability to discontinue steroids for ≥6 months [33% (6/18) vs. 0% (0/19)]. Eighty percent of rindopepimut-treated patients achieved robust anti-EGFRvIII titers (≥1:12,800), which were associated with prolonged survival (HR ¼ 0.17; 95% CI, 0.07-0.45; P < 0.0001). Conclusions: Our randomized trial supports the potential for targeted immunotherapy among patients with GBM, but the therapeutic benefit requires validation due to the small sample size and potential heterogeneity of bevacizumab response among recurrent patients with GBM.
AB - Purpose: Rindopepimut is a vaccine targeting the tumor-specific EGF driver mutation, EGFRvIII. The ReACT study investigated whether the addition of rindopepimut to standard bevacizumab improved outcome for patients with relapsed, EGFRvIII-positive glioblastoma. Patients and Methods: In this double-blind, randomized, phase II study (NCT01498328) conducted at 26 hospitals in the United States, bevacizumab-native patients with recurrent EGFRvIII-positive glioblastoma were randomized to receive rindopepimut or a control injection of keyhole limpet hemocyanin, each concurrent with bevacizumab. The primary endpoint was 6-month progression-free survival (PFS6) by central review with a one-sided significance of 0.2. Results: Between May 2012 and 2014, 73 patients were randomized (36 rindopepimut, 37 control). Rindopepimut toxicity included transient, low-grade local reactions. As primary endpoint, PFS6 was 28% (10/36) for rindopepimut compared with 16% (6/37) for control (P ¼ 0.12, one-sided). Secondary and exploratory endpoints also favored the rindopepimut group including a statistically significant survival advantage [HR, 0.53; 95% confidence interval (CI), 0.32-0.88; two-sided log-rank P ¼ 0.01], a higher ORR [30% (9/30) vs. 18% (6/34; P ¼ 0.38)], median duration of response [7.8 months (95% CI, 3.5-22.2) vs. 5.6 (95% CI, 3.7-7.4)], and ability to discontinue steroids for ≥6 months [33% (6/18) vs. 0% (0/19)]. Eighty percent of rindopepimut-treated patients achieved robust anti-EGFRvIII titers (≥1:12,800), which were associated with prolonged survival (HR ¼ 0.17; 95% CI, 0.07-0.45; P < 0.0001). Conclusions: Our randomized trial supports the potential for targeted immunotherapy among patients with GBM, but the therapeutic benefit requires validation due to the small sample size and potential heterogeneity of bevacizumab response among recurrent patients with GBM.
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U2 - 10.1158/1078-0432.CCR-18-1140
DO - 10.1158/1078-0432.CCR-18-1140
M3 - Article
C2 - 32034072
AN - SCOPUS:85082926477
VL - 26
SP - 1586
EP - 1594
JO - Clinical Cancer Research
JF - Clinical Cancer Research
SN - 1078-0432
IS - 7
ER -