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Clin Cancer Res. 2020 Feb 7. doi: 10.1158/1078-0432.CCR-18-1140. [Epub ahead of print]

Rindopepimut with Bevacizumab for Patients with Relapsed EGFRvIII-Expressing Glioblastoma (ReACT): Results of a Double-Blind Randomized Phase II Trial.

Author information

1
Dana-Farber Cancer Institute, Boston, Massachusetts.
2
Duke University Medical Center, Durham, North Carolina.
3
Saint Francis Hospital and Medical Center, Hartford, Connecticut.
4
University of Pennsylvania, Philadelphia, Pennsylvania.
5
Washington University, St. Louis, Missouri.
6
Baylor Research Institute, Dallas, Texas.
7
University of Alabama at Birmingham, Birmingham, Alabama.
8
Stanford University School of Medicine, Stanford, California.
9
UC Irvine Medical Center, Irvine, California.
10
University of Chicago, Chicago, Illinois.
11
Barrow Neurological Institute, Phoenix, Arizona.
12
Department of Neurosciences, Winthrop University Hospital, Mineola, New York.
13
University of Washington School of Medicine, Seattle, Washington.
14
Scott Cruickshank and Associates, Santa Barbara, California.
15
Celldex Therapeutics, Inc., Hampton, New Jersey.

Abstract

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-naïve 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 = 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 = 0.01], a higher ORR [30% (9/30) vs. 18% (6/34; P = 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 = 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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