The use of immunotherapy agents in gastrointestinal cancer is under investigation in multiple ongoing clinical trials.1 Immunotherapy agents help the immune system to recognize and target cancer cells.1 There are several types used in cancer therapy, including immune checkpoint inhibitors, monoclonal antibodies, T-cell transfer therapy, and vaccines.1 For example, pembrolizumab is an immune checkpoint inhibitor that inhibits PD-1 to enhance T-cell immunity.1 Despite the development of multiple immunotherapy agents, many patients fail to respond well to them, highlighting the need to continue to develop new cancer therapies.1 One approach is targeting phosphatidylserine (PS), a negatively charged amino-phospholipid that is mainly located on the cell inner membrane leaflet, but also found on the outer leaflet and in certain vesicle membranes.1 PS that is present in vesicle membranes is involved in the progression of a variety of diseases; PS on tumor and immune cells leads to immune system suppression helping to promote tumor proliferation.1 Bavituximab is a human–mouse chimeric monoclonal antibody that works by binding to PS and indirectly exerting antitumor immunity effects and inducing tumor-associated endothelial cell cytotoxicity.1 This makes bavituximab an attractive antitumor therapeutic study candidate.
Chau and colleagues studied the use of 3 mg/kg bavituximab every week in combination with 200 mg of pembrolizumab every 3 weeks in previously treated patients with advanced gastric or gastroesophageal junction cancer in a phase 2, multicenter study. There were 75 participants enrolled in the study who were divided into 2 cohorts. Group 1 consisted of 61 patients who were naïve to checkpoint inhibitors. Group 2 had 14 patients who previously relapsed on a checkpoint inhibitor. Antitumor activity, tolerability, and safety of the combination therapy were assessed during the study. The XernaTM TME Panel was used to analyze prespecified biomarkers in pretreatment biopsies. The overall response rate (ORR) in group 1 participants was 13%. When group 1 subgroups were analyzed, ORR was 14% in microsatellite-stable patients, 18% in patients with a combined positive score (CPS) <1, and 13% in patients with CPS ≥1. Xerna TME Panel–positive patients had an ORR of 22% and in negative patients the ORR was 4%. In microsatellite-stable patients with a neutrophil-to-lymphocyte ratio <4 in group 1, the ORR was 18%. Treatment-related adverse event (TRAE) evaluation found no grade 4 or 5 TRAEs. Grade 3 TRAEs included anemia in 14% of patients, and 6% of patients had ascites and increased aspartate aminotransferase levels.
Bavituximab in combination with pembrolizumab demonstrated antitumor activity and was well-tolerated in patients with advanced gastric or gastroesophageal junction cancer.
Source
Chau I, Culm-Merdek K, Bendell J, et al. Phase II study of bavituximab (bavi), a first-in-class antibody targeting phosphatidylserine (PS), plus pembrolizumab (pembro) in advanced gastric or gastroesophageal junction (GEJ) cancer. Ann Oncol. 2021;32(suppl_5):S1050.
Reference
- Chang W, Fa H, Xiao D, Wang J. Targeting phosphatidylserine for cancer therapy: prospects and challenges. Theranostics. 2020;10:9214-9229.