Analyze physiologic MRI changes during treatment with bavituximab, radiation, and temozolomide.

Glioblastoma and tumor endothelial cells express phosphatidylserine, 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 phosphatidylserine, 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 phosphatidylserine blockade, radiation, and temozolomide.

In this ongoing phase II trial (NCT03139916), adult patients with IDH-wild-type newly diagnosed glioblastoma receive 6 weeks of chemoradiation, followed by 6 cycles of adjuvant temozolomide (C1-C6 aTMZ). Bavituximab (3 mg/kg) is given weekly, starting week 1 of chemoradiation, for 18 weeks with the option to continue if tolerated. Physiologic MRIs are performed pre-treatment, pre-C1, pre-C3, and pre-C5 aTMZ. Within the enhancing tumor region, median tumor K^trans (reflecting vascular permeability) and relative cerebral blood volume (rCBV) were measured. Median percent changes during treatment were compared to pre-treatment values.

Imaging data for 25 of 33 patients were analyzed (10 with MGMT promoter methylation). All patients underwent pre-treatment scans. 13 had evaluable pre-C1 and 8 pre-C3 scans. On pre-C1 MRIs, enhancing volume decreased by 39%. There was no significant change in tumor K^trans and rCBV. On pre-C3 MRIs, enhancing volume decreased by 11%. K^trans and rCBV decreased by 17% and 21%, respectively. Five patients had radiographic disease progression after a median 2.6 months and 1 patient died 76 days after diagnosis due to disease progression. Bavituximab safety profile was consistent with previously reported studies.

Combining bavituximab with radiation and temozolomide results in decreased enhancing tumor volume, permeability, and cerebral perfusion. Imaging biomarker evaluation is ongoing to investigate the correlation between bavituximab, MRI changes, and survival.