Bavituximab Pembrolizumab Combination Demonstrates Antitumor Activity in Patients with Pretreated Advanced Gastric or Gastroesophageal Junction Cancer

Web Exclusives —November 16, 2021

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

  1. Chang W, Fa H, Xiao D, Wang J. Targeting phosphatidylserine for cancer therapy: prospects and challenges. Theranostics. 2020;10:9214-9229.
Related Articles
Nivolumab Demonstrates Significant Overall Survival Benefits in Patients with Previously Treated Esophageal Squamous-Cell Carcinoma Compared with Chemotherapy
Web Exclusives
In a follow-up analysis, second-line nivolumab in advanced/recurrent esophageal squamous-cell carcinoma showed significant median overall survival benefit compared with chemotherapy.
Trifluridine/Tipiracil and Ramucirumab Demonstrate Antitumor Activity in Previously Treated Unresectable Advanced Gastric or Gastroesophageal Cancer
Web Exclusives
Promising antitumor activity and a tolerable safety profile were found in patients with previously treated gastric or gastroesophageal cancer treated with trifluridine/tipiracil combined with ramucirumab.
Insertion-Deletion Rate Is Associated with Clinical Outcomes in Nivolumab-Treated Gastric Cancer
Web Exclusives
Insertion-deletion rate and high tumor mutation burden in advanced gastric cancer was found to be associated with favorable progression-free survival and overall survival in patients treated with nivolumab.
Last modified: November 16, 2021

Subscribe to the Journal of Oncology Navigation & Survivorship®

To sign up for our print publication or e-newsletter, please enter your contact information below.

  • First Name *
    Last Name *
     
     
    Profession or Role
    Primary Specialty or Disease State
    Country
  • Please enter your mailing address.

    Address
     
    Address Line 2
    City
     
    State
    Zip Code