A phase I/II study of nivolumab, paclitaxel, and ramucirumab as second-line in advanced gastric cancer.

Abstract

352 Background: Synergistic anti-tumor effect induced by simultaneous blockade of PD-1 and taxanes, and PD-1 and VEGFR-2 has been reported. A phase I/II study was conducted to investigate the safety and efficacy of nivolumab (Nivo) with paclitaxel (PTX) plus ramucirumab (Ram), which is the standard treatment as the second-line treatment for advanced gastric cancer (AGC). Methods: AGC patients (pts) with measurable lesions, ECOG PS 0-1, and disease progression on the first-line chemotherapy with fluoropyrimidine and platinum were eligible. Pts 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) (Level 1), every 4 weeks. After feasibility was evaluated in 6 pts (phase I part), additional 37 pts were enrolled in a phase II part with the primary endpoint of 6-month progression-free survival (PFS) rate. The combined positive score (CPS) is defined as the number of PD-L1 positive cells (tumor cells, macrophages, and lymphocytes) divided by the total number of viable tumor cells. Results: Fourty-three AGC pts were enrolled: median age, 66 years; ECOG PS 1, 48.8%; and CPS ≥1, 60.5%. Dose limiting toxicities were observed in 2 pts in the phase I part and recommended dose was determined as Level 1. ORR was 37.2% (95%CI, 23.0-53.5%): 46.2% (95%CI, 26.6-66.6%) in CPS≥1 pts and 30.8% (95%CI, 9.1-61.4%) in CPS < 1 pts. With a median follow-up time of 16.8 months, 6-month PFS rate was 46.4% (80% CI, 36.4-55.8%) ( P= 0.067): 57.7% (95%CI, 36.8-73.9%) in CPS≥1 pts and 38.5% (95%CI, 14.1-62.9%) in CPS < 1 pts. Median PFS was 5.1 months (95%CI, 4.5-6.5 months). 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 pts and 8.0 months (95%CI, 4.8-24.1 months) in CPS < 1 pts, and 18-months survival rate was 32.1% (95%CI, 18.2-46.8%). Conclusions: Nivo with PTX plus Ram demonstrated promising antitumor activity as the 2nd-line treatment for AGC pts with manageable toxicities. Clinical trial information: UMIN000025947.