VOYAGER (KSCC1902): A single-arm, multicenter, phase II study of early induction of nivolumab during second-line treatment with taxane ± ramucirumab for advanced gastric or gastro-esophageal junction cancer.

Abstract

4028 Background: Although nivolumab prolonged overall survival in 3rd or later line treatment for advanced gastric cancer in the ATTRACTION-2 study, only a small number of patients respond or achieve stable disease. Previous reports have shown that low tumor burden at the start of treatment was potentially associated with efficacy to immunotherapy in some types of tumors, but it has not been studied in advanced gastric cancer. We conducted a clinical trial to evaluate the early induction of nivolumab. Methods: Eligible patients were unresectable advanced or recurrent gastric or gastro-esophageal junction cancer, histologically confirmed to be adenocarcinoma regardless of PD-L1 expression. Patients who were refractory to or intolerant of fluoropyrimidines had a complete or partial response after at least three cycles of taxane ± ramucirumab, and were confirmed to be either of the following conditions; disease progression by imaging tests, an increase of tumor markers, exacerbation of symptoms, and intolerant of pretreatment. Patients received 240mg/body nivolumab every 2 weeks. The primary endpoint was the rate of progression-free survival (PFS) at 6 months (M), and the secondary endpoints included safety, overall survival (OS), response rate (RR), time to treatment failure (TTF), and duration of response (DOR). Based on assuming a threshold PFS at 6M of 16% and an expected PFS of 30% with the early induction of nivolumab, 39 patients were required for a power of 0.8 with a one-sided α of 0.1. Results: Between September 2019 and February 2021, 42 patients were enrolled in this study. The characteristics of patients were male/female: 28/14, median age: 71 years (range: 39-87), and performance status 0/1/2: 21/19/2. The PFS at 6M was 35.7% (80% confidence interval 26.4-45.1%), which means this trial met the primary endpoint. The median PFS and OS were 4.0M (95%CI:2.3–5.7) and 10.9M (95%CI:9.9–16.0), respectively. Of 34 patients with baseline target legions, RR was 17.5% (all confirmed partial response) and the rate of stable disease was 41.2%. TTF, and DOR were 3.6M (95%CI:2.2–5.1), and 14.3M (95%CI:3.9–14.3), respectively. No new safety signals were observed. Conclusions: This study demonstrated an improvement of PFS at 6M in patients with advanced gastric cancer and might justify the strategy of early induction of nivolumab. Clinical trial information: jRCTs071190025.