IT-30ReACT: A PHASE II STUDY OF RINDOPEPIMUT VACCINE (CDX-110) PLUS BEVACIZUMAB IN RELAPSED GLIOBLASTOMA
| Autor: | Michael J. Yellin, David A. Reardon, Rimas V. Lukas, James M. Schuster, J. Paul Duic, Lynn Aneiro, Lynn S. Ashby, John Sampson, Thomas Hawthorne, David Tran, Gordon Li, Annick Desjardins, Karen Fink, Jennifer Green, Thomas P. Davis, Louis B. Nabors |
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| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
Oncology
Cancer Research medicine.medical_specialty Bevacizumab biology business.industry Phases of clinical research EGFRvIII Peptide medicine.disease Titer Abstracts Refractory Internal medicine Immunology Toxicity Injection site reaction medicine biology.protein Neurology (clinical) business Keyhole limpet hemocyanin medicine.drug |
| Popis: | BACKGROUND: EGFRvIII, a constitutively active tumorigenic EGFR deletion mutation, is linked to poor long-term survival. The investigational vaccine rindopepimut consists of the unique EGFRvIII peptide sequence conjugated to keyhole limpet hemocyanin (KLH), delivered intradermally with GM-CSF. Three phase II studies of rindopepimut in newly diagnosed, resected, EGFRvIII+ glioblastoma have shown encouraging PFS and OS. Bevacizumab (BV), an agent with activity in glioblastoma, may augment EGFRvIII-specific immune response and antitumor activity through inhibition of VEGF and its immunosuppressive properties. METHODS: “ReACT” is a Phase II study of rindopepimut plus BV in patients with 1st or 2nd relapse of EGFRvIII+ glioblastoma. BV-naive pts (Group 1; n = 70) are randomized 1:1 to BV plus double-blinded injection of either rindopepimut or control (KLH). BV-refractory patients (progression within 2 months of BV; Group 2/2C, n = 98) receive BV plus open-label rindopepimut. RESULTS: 234/700 (33%) screened patients are EGFRvIII+. 115 patients (Group 1 = 72, Group 2/2C = 43) are enrolled. Primary toxicity is Grade 1-2 injection site reaction. In group 1, for rindopepimut + BV vs. KLH + BV, objective response rate (ORR; investigator-assessed, RANO criteria) is 23% (6/26) vs 12% (3/25) [35% vs. 20% including responses observed at a single time point (“unconfirmed”)]. In Group 2/2C (evaluable n = 30), one unconfirmed PR and one sustained PR (patient continues treatment at 15 months) occurred. Two additional patients had pre-study progression >2 months after BV; one maintained a CR for 11.1 months (peak anti-EGFRvIII titer = 1:3,276,800), while the second experienced an unconfirmed CR. Median peak rindopepimut-induced anti-EGFRvIII humoral response is 1:25,600 [range |
| Databáze: | OpenAIRE |
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