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  • ReACT: Overall Survival from a Randomized Phase II Study of Rindopepimut (CDX-110) Plus Bevacizumab in Relapsed Glioblastoma

    Final Number:
    107

    Authors:
    D. Reardon; J. Schuster; D. Tran; K. Fink; L. Nabors; G. Li; D. Bota; R. Lukas; A. Desjardins; L. Ashby; J. Duic; M. Mrugala; A. Werner; T. Hawthorne; Y. He; J. Green; M. Yellin; C. Turner; T. Davis; J. Sampson

    Study Design:
    Clinical Trial

    Subject Category:

    Meeting: Congress of Neurological Surgeons 2015 Annual Meeting

    Introduction: EGFRvIII, a constitutively active EGFR deletion driver mutation, is associated with poor long-term survival in glioblastoma (GB). The investigational vaccine rindopepimut consists of a peptide sequence unique to EGFRvIII conjugated to keyhole limpet hemocyanin (KLH), delivered intradermally with GM-CSF. Three phase II studies in newly diagnosed, resected, EGFRvIII+ GB demonstrated encouraging progression-free survival (PFS), overall survival (OS) and safety profile. Compassionate use experience suggests that rindopepimut may also provide benefit in relapsed GB, particularly with agents such as bevacizumab (BV).

    Methods: In the Phase II “ReACT” study, BV-naïve pts in 1st or 2nd relapse with EGFRvIII+ GB were randomized 1:1 to BV plus double-blinded injection of rindopepimut or control (KLH). Endpoints: 6-month PFS (PFS6; primary), objective response rate (ORR), PFS, OS and safety.

    Results: Accrual is complete (n=72); study follow-up continues (n=30). Primary rindopepimut toxicity is Grade 1-2 injection site reaction. For rindopepimut+BV vs. KLH+BV (per investigator; RANO criteria): PFS6=27% (9/33) vs. 11% (4/35) (p=0.048, 1-side chi-square test); ORR=24% (7/29) vs. 17% (5/30). Central PFS/ORR assessment is underway. Median (95% CI) OS=12.0 (9.7, -) vs. 8.8 (6.8, 11.4) months (HR=0.47 [0.25, 0.91]; p=0.0208), with 8 vs. 4 pts progression-free. OS analyses favor rindopepimut including when adjusted for various prognostic factors. Rindopepimut induced robust anti-EGFRvIII titers (1:12,800-1:6,553,600) in 80% of pts. Rapid titer generation was associated with prolonged OS (HR=0.47 [0.18, 1.27]; p=0.128) within the rindopepimut arm, and was most frequent in pts with KPS >=90 (odds ratio=9.75; p=0.007). Evaluation of humoral response quality and HLA typing vs. outcome are underway. In an additional cohort of BV-exposed pts (n=53), four pts experienced objective tumor response.

    Conclusions: These near-final data show that rindopepimut induces potent EGFRvIII-specific immune response and tumor regression, and appears to significantly prolong survival when administered with BV, in pts with relapsed GB.

    Patient Care: This abstract describes a study evaluating whether the addition of a EGFRvIII targeted vaccine to current approved therapy can improve progression-free and overall survival for patients with recurrent glioblastoma

    Learning Objectives: By the conclusion of this session, participants should be able to understand the potential role of EGFRvIII targeted vaccine in the treatment of patients with recurrent glioblastoma.

    References:

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