CTNI-67. DUAL INHIBITION OF POST-RADIOGENIC ANGIO-VASCULOGENESIS BY OLAPTESED PEGOL (NOX-A12) AND BEVACIZUMAB IN GLIOBLASTOMA – INTERIM DATA FROM THE FIRST EXPANSION ARM OF THE GERMAN PHASE 1/2 GLORIA TRIAL

Abstract BACKGROUND We recently reported favorable safety, promising clinical efficacy and immunohistochemical indicators of response after radiotherapy (RT) plus escalating doses the CXCL12-neutralizing RNA-Spiegelmer olaptesed pegol (NOX-A12) for glioblastoma in German multicenter phase 1/2 GLORIA trial (NCT04121455). Here, we report outcomes RT dual inhibition vasculogenesis angiogenesis (bevacizumab). METHODS After establishing safety monotherapy arm, enrolled six patients with incompletely resected GBM, ECOG ≤ 2, age ≥ 18 without MGMT promoter hypermethylation into a pre-planned expansion arm. Patients received standard (60 Gy 30 fractions), continuous i.v. infusions NOX-A12 (600 mg/week) bevacizumab (10 mg/kg q2w). The primary endpoint was safety. Secondary endpoints included radiographic response, perfusion/diffusion imaging neurologic performance. RESULTS Dual treatment well-tolerated safe. Of all G 2 AEs (n = 37), two G2 events (5.4%) were deemed related to NOX-A12. There no dose-limiting toxicities treatment-related deaths. Longitudinal NANO assessment revealed stable functioning patients. Five out achieved partial responses (PRs) as per mRANO week 9. All PRs remained durable at median follow up 5.6 months (range 3.6 9.3 months). No progression occurred. mean best -65.9% (-13.3% -99.9%) target lesion sums -92.1% (-76.2% -100%) non-target (NTL) sums. In three NTL least one disappeared. change from baseline highly perfused-tumor fraction -84.5% (-51.9% apparent diffusion coefficient 20.1% (-24.5% 59.1%). CONCLUSION Interim data ongoing confirm previously established profile suggest improved post-radiogenic angio- by addition bevacizumab.