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

Bavi, a monoclonal antibody designed to inhibit the immunosuppressive effects of PS through interaction with TIM andTAM receptor family members in the tumor microenvironment (TME), is being evaluated in combination with pembro in patients with advanced gastric and GEJ cancer. ONCG100 is a phase II, multicenter, open-label, two-cohort global study designed to assess the safety, tolerability, and antitumor activity of bavi (3 mg/kg, QW) in combination with pembro (200 mg, Q3W) in patients with advanced gastric or GEJ cancer regardless of programed death-ligand 1 (PD-L1) status who have progressed on ≥1 prior standard therapy (NCT04099641). Patients were either naïve to checkpoint inhibitors (CPIs, Group 1) or previously relapsed on a CPI (Group 2); if known, MSI-H patients were excluded. Pre-treatment biopsies were required for pre-specified biomarker analysis using the Xerna™ TME Panel. A total of 75 patients have been enrolled (Group 1 n=61, Group 2 = 14). The most frequent grade 3 TEAEs were anemia (14%), ascites and increased aspartate aminotransferase (6%). There were no related grade 4 or grade 5 TEAEs. Antitumor activity for Group 1 is summarized in the Table.Table: 1386PAnti-tumor activity in CPI naïve patients1CPI Naïve PatientsCPI Naïve Patient SubgroupsMSSCPSXernaTMTME Panel<1≥1PosNegORR13% (8/61)14% (6/43)18% (3/17)13%(5/40)22% (7/32)4% (1/24)ORR in MSS,NLR <418% (7/39)19% (5/27)20%(2/10)19%(5/26)33% (7/21)0%(0/13)1 Includes MSS status unknown. Open table in a new tab 1 Includes MSS status unknown. The combination of bavi + pembro is well tolerated and active in gastric cancer, including in patient with CPS<1, a group less responsive to CPI. In addition, the Xerna™ TME Panel was likely predictive of treatment response. Retrospective analysis suggests baseline NLR may have a prognostic or predictive role. The anti-tumor activity of bavi + pembro across high and low CPS suggests that bavi sensitizes cancers to CPI activity, potentially expanding the use of the combination to patients typically less responsive to CPIs, and warrants confirmation.