A Multicenter, Dose-Escalation, Open-Label, Phase IIa Clinical Trial to Evaluate the Safety and Efficacy of TTAC-0001 (olinvacimab), a Fully Human Monoclonal Antibody in Patients with Recurrent Glioblastoma

Abstract Introduction The VEGF pathway remains an important target in GBM given its vascularity and autocrine VEGF signalling. Olinvacimab is a fully humanised VEGFR2 monoclonal antibody that binds and inhibits the receptor. This report assesses the safety, dosing schedules and efficacy of olinvacimab in recurrent GBM (rGBM). Methods Adult patients with a measurable lesion, histopathological diagnosis of primary GBM with tumour progression after chemoradiotherapy were included. No prior biologic treatment was allowed. Three dose levels of intravenous olinvacimab were assessed: 8 mg/kg (dose level 1) and 12mg/kg (dose level 2) weekly for 3 out of 4 weeks, and 12 mg/kg weekly (dose level 3). Efficacy was assessed by MRI using RANO criteria. Dynamic Contrast-Enhanced MRIs (DCE-MRIs) were analysed for changes in perfusion parameters during treatment. Results Twelve patients were enrolled in this study: three each in dose levels 1 and 2, and six in dose level 3. The main toxicity was development of grade 1 (67%) and 2 (8%) cutaneous haemangiomas. Common toxicities noted with other VEGF directed therapies- including hypertension, impaired wound healing, and proteinuria- were not seen. The 6-month progression free survival rate was 17%, disease control rate 25%, and the longest response 15 months. No significant difference in perfusion parameters was found between baseline and 1st follow-up DCE-MRI comparing those with stable and progressive disease. ConclusionOlinvacimab was well tolerated across three dose levels and had a distinct toxicity profile. Disease control was seen in 25% of patients and warrants further follow up in further clinical trials.