Initial safety run-in findings with bavituximab plus pembrolizumab in patients with advanced gastric or gastroesophageal cancer.

Abstract

e16537 Background: Bavituximab, an investigational, chimeric monoclonal antibody designed to inhibit the immunosuppressive effects of phosphatidylserine (PS), is being evaluated in combination with pembrolizumab in patients with advanced gastric and gastroesophageal junction (GEJ) cancer. Bavituximab binds in a high-affinity complex with β2-glycoprotein and PS to reverse immunological non-responsiveness and activate multiple immune cell receptors. Post-hoc data from the Phase III Sunrise second-line lung cancer study indicated that patients who progressed on study treatment with bavituximab plus docetaxel and continued with a checkpoint inhibitor showed significantly improved overall survival. Cumulative data suggest that bavituximab may potentiate pembrolizumab-mediated checkpoint inhibition, potentially increasing overall clinical benefit. ONCG100 is a phase 2, multicenter, open-label, single-arm global study designed to assess the safety, tolerability and efficacy of bavituximab and pembrolizumab when administered in combination to advanced gastric or GEJ adenocarcinoma patients, regardless of PD-L1 status, who have progressed on or after at least one prior standard therapy (NCT04099641). Methods: The safety run-in phase of the trial evaluated the safety and tolerability of de-escalating doses of bavituximab when administered in combination with the approved dose and schedule of pembrolizumab (200mg, Q3W). Adverse events were evaluated by CTCAE v5.0. Results: Three patients enrolled and completed the safety-run in phase of the study where bavituximab was administered at the starting dose of 3 mg/kg QW in combination with pembrolizumab. There were no dose-limiting toxicities observed during the 21-day monitoring period. A total of 4 treatment emergent adverse events were observed; 2 of which were reported as related to treatment with bavituximab (arthralgia and fatigue, both grade 1). There was one treatment-unrelated SAE reported (chylous ascites, grade 2), which resolved allowing the patient to continue treatment. Conclusions: The 3 mg/kg dose of bavituximab was readily combined during the safety run-in phase of the study with the approved dose of pembrolizumab. The AE profiles for this combination were manageable and expected given the known profiles of each agent. Based upon these findings, the recommended dose for expansion for the combination was declared and the expansion phase of the study opened. Updated safety data from the study will be presented. Clinical trial information: NCT04099641 .