Overall survival results from the phase 2 NIVOFGFR2 study of first-line nivolumab plus CAPOX in patients with FGFR2-positive, PD-L1-positive metastatic gastric cancer.

4042 Background: The interim analysis of the NIVOFGFR2 phase 2 study showed a 1-year PFS rate of 30.4% in patients with FGFR2-positive, PD-L1-positive metastatic gastric cancer treated with the combination of nivolumab and CAPOX in the first-line setting (GI ASCO 2024). Here, we present data on overall survival (OS) and second-line PFS (PFS2). Methods: In this single-arm, multi-center, phase 2 study, eligible patients had metastatic untreated HER2-negative gastric adenocarcinoma, and their PD-L1 expression (CPS≥5; DAKO 28-8) and FGFR2 status (moderate (2+) and strong (3+) membranous staining in more than 1% of tumor cells; Abсam EPR24075-418) were centrally confirmed by IHC. Patients were treated with nivolumab 360 mg in combination with capecitabine and oxaliplatin every 3 weeks till disease progression or unacceptable toxicity. Following progression, the planned treatment regimen included ramucirumab at a dose of 8 mg/kg with paclitaxel. The primary endpoint was the 1-year PFS rate and secondary endpoints included median PFS, PFS2, OS, objective response rate (ORR), and the Grade ≥3 adverse events (AEs) rate. Results: Twenty-three 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%, previous surgery 61%, adjuvant/neoadjuvant therapy 17%, time to metastatic disease <1 year 48%). Two (8.7%) patients remain on first-line therapy, 19 (82.6%) have received second-line ramucirumab and paclitaxel, and 10 (43.5%) have received 3 or more lines of therapy. The median follow-up for OS was 17.3 months, with 7 patients still alive. We present the updated efficacy and toxicity results (Table). Conclusions: Despite the modest efficacy of nivolumab with CAPOX in the first-line setting, a favorable median OS was observed, possibly attributable to the incorporation of ramucirumab with paclitaxel in the second-line treatment of FGFR2-positive, PD-L1-positive metastatic gastric cancer. Clinical trial information: NCT05859477 . [Table: see text]