A phase II, open-label, randomized study to evaluate the efficacy and safety of andecaliximab combined with nivolumab versus nivolumab alone in subjects with unresectable or recurrent gastric or gastroesophageal junction adenocarcinoma.

Abstract

75 Background: Andecaliximab (ADX) is a monoclonal antibody that inhibits matrix metalloproteinase 9 (MMP9). Preclinical studies suggest that MMP9 inhibition relieves immune suppression and promotes T-cell infiltration to potentiate checkpoint blockade. Methods: Phase 2, open-label, randomized study of the efficacy and safety of ADX + nivolumab (NIVO) vs. NIVO alone in patients with pre-treated metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma. Patients were randomized to either ADX 800 mg IV + NIVO 3 mg/kg IV, or NIVO 3 mg/kg IV alone, and stratified by tumor PD-L1 status. Treatment was administered every 2 weeks. Re-staging CT scans were performed every 8 weeks to evaluate response. Primary endpoint: objective response rate (ORR). Secondary endpoints: progression-free survival (PFS), overall survival (OS), and adverse events (AEs). Results: Of the 144 patients randomized, 141 were treated, 109 (76%) completed tumor assessment. 81% of patients were white, with 69% male and a mean (SD) age of 59 (12) years. ORR (95% CI) was 11.1% (4.9–20.7%) in patients receiving ADX + NIVO, and 6.9% (2.3–15.5%) in those receiving NIVO alone, p = 0.6. Kaplan-Meier estimated median (95% CI) PFS was 1.8 (1.8–2.0) months in patients receiving ADX + NIVO, and 1.9 (1.7–1.9) months in those receiving NIVO alone, p = 0.2. Kaplan-Meier estimated median (95% CI) OS was 7.2 (5.2–9.1) months in patients receiving ADX + NIVO, and 5.9 (3.5–8.6) months in those receiving NIVO alone, p = 0.4. AEs leading to treatment discontinuation occurred in 1 patient in the ADX + NIVO group, and in 1 patient in NIVO-only group. PD-L1 and mismatch repair deficient subgroup analyses will be presented. Exploratory biomarker analyses will be submitted separately. Conclusions: Addition of ADX to NIVO did not improve ORR, PFS, or OS compared with NIVO alone in patients with pre-treated metastatic gastric or GEJ adenocarcinoma. Combination of ADX with NIVO had a favorable safety and tolerability profile. Clinical trial information: NCT02864381.