Efficacy and safety of nivolumab and CapeOX in patients with previously untreated FGFR2-positive, PD-L1-positive advanced gastric cancer: A single-arm, multicenter, phase 2 study NIVOFGFR2.

Abstract

303 Background: Nivolumab in combination with chemotherapy has been approved in the first-line treatment of PD-L1-positive metastatic gastric cancer (GC). Fibroblast growth factor receptor 2 (FGFR2) is overexpressed in 30% of patients with GC and is a potential new target for targeted therapy with monoclonal antibodies1 or allosteric extracellular inhibitors.2 The aim of the NIVOFGFR2 study was to evaluate the preliminary efficacy of nivolumab in metastatic GC co-expressing PD-L1 and FGFR2. Methods: In this single-arm, multi-center, phase 2 study, eligible patients had metastatic untreated HER2-negative gastric adenocarcinoma with centrally confirmed expression of PD-L1 (CPS≥5; DAKO 28-8) and FGFR2 (moderate (2+) and strong (3+) membranous staining in more than 1% of tumor cells; Abсam EPR24075-418). Patients received nivolumab 360 mg with CapeOX (capecitabine and oxaliplatin) every 3 weeks. The primary endpoint was 1-year progression-free survival (PFS). Secondary endpoints included median PFS and overall survival (OS), objective response rate (ORR) and Grade ≥3 adverse events rate. Results: Seventy-four HER2-negative patients were screened and23 (31%) patients were enrolled (median age 61 years, men 74%, Caucasian 91%, ECOG PS 1-2 78%, organs with ≥2 metastases 78%; CPS (5-9) 22%, (≥10) 78%). 1-year PFS rate was 30,4%. The median PFS was 6.2 months (95% CI 4.4-7.6). The ORR was 21.7% with 1 complete response. With a median follow-up of 11.8 months at data cutoff, the median OS was not reached. Grade ≥3 treatment-related adverse events were reported in 9 (39.1%) patients. Conclusions: An interim analysis demonstrates modest efficacy and an acceptable safety profile of nivolumab in combination with chemotherapy in patients with FGFR2-positive, PD-L1-positive metastatic GC. Further follow-up is ongoing. 1. Wainberg, Lancet Oncol. 2022. 2. Tsimafeyeu, Invest New Drugs. 2023. Clinical trial information: NCT05859477 .