Phase 2 study of bavituximab (bavi), a first-in-class antibody targeting phosphatidylserine (PS), plus pembrolizumab (P) in advanced gastric or gastroesophageal junction (GEJ) cancer.

Abstract

e16023 Background: Bavi, a monoclonal antibody designed to inhibit the immunosuppressive effects of PS through interaction with TIM/TAM receptor family members in the tumor microenvironment (TME), was evaluated in combination with P in patients with advanced gastric and GEJ cancer. Methods: ONCG100 was a phase 2, multicenter, open-label, two-cohort global study designed to assess the safety, tolerability, and antitumor activity of bavi (3 mg/kg, QW) plus P (200 mg, Q3W) in advanced gastric or GEJ cancer patients who progressed on ≥1 prior standard therapy (NCT04099641). Patients were checkpoint inhibitor (CPI) naive (Grp 1) or CPI relapsed (Grp 2); known MSI-H patients were excluded. RNA expression was analyzed in pre-treatment tumor tissue using the Xerna TME Panel, an RNA-based diagnostic, to prospectively test hypothesis that tumors with high immune or immune-suppressed TME subtypes (B+) are more likely to respond to bavi plus P than high angiogenic/immune-desert TME subtypes (B-). Results: A total of 80 patients enrolled (Grp 1 n=61, Grp 2 = 19). The most frequently reported Grade ≥ 3 treatment emergent adverse events (occurring in ≥10% of patients overall) were anaemia and gastric cancer progression (n= 10/AE). Key efficacy parameters for Grp 1 patients (2L 57.4%) are summarized in Table 1. In Grp 2, the ORR was 5.3% (95% CI: 0.1, 26.0), whereby 0 patients achieved a complete response and only 1 (5.3%) patient achieved a partial response as the best overall response (BOR). In the remaining patients, BOR was stable disease in 9 (47.4%) patients, progressive disease in 8 (42.1%) patients, and not evaluable in 1 (5.3%) patient. Conclusions: The combination of Bavi and P was well tolerated; observed AEs were consistent with known profiles for each agent. Higher ORRs were observed in CPI-naïve patients with B+ status and baseline NLR<4, and of note, in patients with PD-L1 CPS <1. Future studies may be planned to confirm the activity of Bavi in combination with P with patient selection based on a particular genetic signature. Clinical trial information: NCT04099641 . [Table: see text]