MRI changes in patients with newly diagnosed glioblastoma treated as part of a phase II trial with bavituximab, radiation, and temozolomide.

Abstract

2546 Background: Glioblastoma and tumor endothelial cells express phosphatidylserine (PS), a highly immunosuppressive membrane phospholipid. Bavituximab – a chimeric monoclonal antibody – binds to β2-glycoprotein 1 (β2-GP1) to form a complex of β2-GP1 with PS, resulting in immune activation against tumor cells and anti-angiogenic effects. Phase I/II trials in other solid cancers demonstrated response rates up to 75% when bavituximab was given with cytotoxic chemotherapy. Pre-clinical data in glioblastoma models suggested synergistic effects of PS blockade, radiation, and temozolomide. Methods: 33 adult patients with IDH-wild-type, MGMT-methylated or -unmethylated newly diagnosed glioblastoma were enrolled in this phase II trial (NCT03139916) and received 6 weeks of chemoradiation, followed by 6 cycles of adjuvant temozolomide (C1-C6 aTMZ). Bavituximab (3 mg/kg) was given weekly, starting week 1 of chemoradiation, for 18 weeks with the option to continue if tolerated. Physiologic MRIs were performed pre-treatment, pre-C1, pre-C3, and pre-C5 aTMZ. Within the enhancing tumor region, median tumor Ktrans (reflecting vascular permeability) and relative cerebral blood flow (rCBF) were measured. Median percent changes during treatment were compared to pre-treatment values. Results: Median progression-free survival (mPFS) was 8 months. Based on a median overall survival (mOS) of 17.1 months, patients were categorized into above-median survivors (AMS) and below-median survivors (BMS). All patients had pre-treatment scans. 31 had evaluable pre-C1, 25 had pre-C3, and 7 had pre-C5 scans. Compared to BMS, AMS had a greater reuction in enhancing tumor volume and rCBF, and a greater increase in Ktrans during treatment (table). One patient remains on study; 23 patients have died. Bavituximab was well tolerated. Conclusions: mPFS and mOS in patients treated with bavituximab, radiation and temozolomide were comparable to standard chemoradiation and aTMZ. Lower rCBF in AMS may reflect decreased tumor perfusion while higher Ktrans could imply enhanced drug delivery to the tumor. Bavituximab induces changes in tumor vasculature that may improve survival in a subset of patients. Clinical trial information: NCT03139916 . [Table: see text]