Multicenter Phase I/II Study of Nivolumab Combined with Paclitaxel Plus Ramucirumab as Second-line Treatment in Patients with Advanced Gastric Cancer

Abstract

Purpose: We conducted a phase I/II study to investigate the safety and efficacy of nivolumab (NIVO) with paclitaxel (PTX) plus ramucirumab (RAM). Experimental Design: Patients with advanced gastric cancer (AGC) refractory to first-line chemotherapy were included. Patients received NIVO (3 mg/kg on days 1 and 15) combined with PTX (80 mg/m2 on days 1, 8, and 15) and RAM (8 mg/kg on days 1 and 15) every 4 weeks. After feasibility evaluation in 6 patients (phase I), 37 additional patients were enrolled to the phase II with the primary endpoint of 6-month progression-free survival (PFS) rate with two-sided 80% CI. The combined positive score (CPS) was defined as the number of programmed death-ligand 1-positive cells divided by the total number of viable tumor cells, multiplied by 100. Results: Forty-three patients were enrolled. Of these, 60.5% had CPS≥1. Dose-limiting toxicities were observed in 2 patients, and the recommended dose was determined as level 1. Thirty-nine (90.7%) patients experienced treatment-related adverse events ≥ grade 3 and 14 (32.6%) patients experienced immune-related adverse events ≥ grade 3. The overall response rate was 37.2% (95%CI, 23.0%-53.5%) and the 6-month PFS rate was 46.5% (80% CI, 36.4%-55.8%) (P=0.067). Median survival time was 13.1 months (95%CI, 8.0-16.6 months): 13.8 months (95%CI, 8.0-19.5 months) in CPS≥1 patients and 8.0 months (95%CI, 4.8-24.1 months) in CPS<1 patients. Conclusions: NIVO with PTX plus RAM demonstrated promising anti-tumor activity with manageable toxicities as second-line treatment for AGC.