Ian Chau, MD from Royal Marsden Hospital discusses the ASCO abstract Initial safety run-in findings with bavituximab plus pembrolizumab in patients with advanced gastric or gastroesophageal cancer.
Context:
In patients with advanced gastric and gastroesophageal junction (GEJ) cancer, bavituximab, an investigational, chimeric monoclonal antibody engineered to inhibit the immunosuppressive effects of phosphatidylserine (PS), is being tested in combination with pembrolizumab. To reverse immunological non-responsiveness and stimulate multiple immune cell receptors, bavituximab binds to β2-glycoprotein and PS in a high-affinity complex. Post-hoc results from the Phase III Sunrise second-line lung cancer trial showed that overall survival was substantially improved in patients who advanced with bavituximab plus docetaxel and proceeded with a checkpoint inhibitor. Cumulative data indicate that bavituximab can potentiate inhibition of the checkpoint mediated by pembrolizumab, potentially increasing overall clinical benefit. ONCG100 is a multicenter, open-label, single-arm, phase 2 global study designed to evaluate the protection, tolerability, and efficacy of bavituximab and pembrolizumab in combination with advanced gastric or GEJ adenocarcinoma patients, irrespective of PD-L1 status, who have progressed on or after at least one previous standard therapy (NCT04099641).
Methodology:
The safety run-in phase of the trial assessed the safety and tolerability of bavituximab de-escalating doses when administered in conjunction with the approved pembrolizumab dose and schedule (200 mg, Q3W). Adverse events have been measured by CTCAE v5.0.0.Â
Outcomes:
Three patients were enrolled and completed the safety step of the study in which bavituximab, in conjunction with pembrolizumab, was administered at the starting dose of 3 mg/kg QW. During the 21-day monitoring period, no dose-limiting toxicities were detected. A total of 4 emerging treatment adverse reactions were observed, of which 2 were identified as related to bavituximab therapy (arthralgia and fatigue, both grade 1). One treatment-unrelated SAE (chylous ascites, grade 2) was identified and resolved to allow the patient to continue treatment.
Conclusions:
The 3 mg/kg dose of bavituximab was readily combined with the approved dose of pembrolizumab during the safety run-in phase of the study. Given each agent’s known profiles, the AE profiles for this combination were manageable and planned. On the basis of these results, the recommended expansion dose for the combination was announced and the study expansion stage was opened. It will present updated safety data from the report. Data on clinical trials: NCT04099641.