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107 ReACT: Overall Survival From a Randomized Phase II Study of Rindopepimut (CDX-110) Plus Bevacizumab in Relapsed Glioblastoma. Neurosurgery Reardon, D. A., Schuster, J. M., Tran, D. D., Fink, K. L., Nabors, L. B., Li, G., Bota, D. A., Lukas, R. V., Desjardins, A., Ashby, L. S., Duic, J. P., Mrugala, M. M., Werner, A., Hawthorne, T., He, Y., Green, J., Yellin, M. J., Turner, C. D., Davis, T. A., Sampson, J. H. 2015; 62 Suppl 1, CLINICAL NEUROSURGERY: 198-199

Abstract

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 granulocyte macrophage colony-stimulating factor. 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).In the Phase II "ReACT" study, BV-naïve patients in 1st or 2nd relapse with EGFRvIII+ GB were randomly assigned 1:1 to BV plus double-blinded injection of rindopepimut or control (KLH).6-month PFS (PFS6; primary), objective response rate (ORR), PFS, OS, and safety.Accrual is complete (n = 72); study follow-up continues (n = 30). Primary rindopepimut toxicity is grade 1 to 2 injection site reaction. For rindopepimut + BV vs KLH + BV (per investigator; RANO criteria): PFS6 = 27% (9/33) vs 11% (4/35) (P = .048, 1-side ? 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 = .0208), with 8 vs 4 patients progression-free. OS analyses favor rindopepimut including when adjusted for various prognostic factors. Rindopepimut induced robust anti-EGFRvIII titers (1:12800-1:6553600) in 80% of patients. Rapid titer generation was associated with prolonged OS (HR = 0.47 [0.18, 1.27]; P = .128) within the rindopepimut arm, and was most frequent in patients with KPS = 90 (odds ratio = 9.75; P = .007). Evaluation of humoral response quality and HLA typing vs outcome are underway. In an additional cohort of BV-exposed patients (n = 53), four patients experienced objective tumor response.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 patients with relapsed GB.

View details for DOI 10.1227/01.neu.0000467069.86811.3f

View details for PubMedID 26181953