Neoadjuvant nivolumab monotherapy in patients with resectable gastric cancer: Preliminary results from a multicenter study.
Authors: Takiguchi Shuji , Shitara Kohei , Takiguchi Noriaki , Ito Seiji , Kochi Mitsugu , Horinouchi Hidehito , Kinoshita Takahiro , Muro Kei , Yoshikawa Takaki , Hasegawa Hirotaka , Nishikawa Hiroyoshi , Kodera Yasuhiro 
Published: June 2021

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Background: In recent years, several studies suggest that neoadjuvant treatment improve outcomes of patients with resectable advanced gastric cancer (GC). In addition, nivolumab has demonstrated clinical efficacy in multiple types of advanced cancer, and the efficacy of neoadjuvant nivolumab monotherapy has been suggested in a past clinical trial in patients with resectable non-small cell lung cancer (NSCLC). Therefore, this phase I study was planned to evaluate the safety and efficacy of neoadjuvant nivolumab monotherapy in patients with resectable GC or NSCLC. Here we report preliminary results from GC patients. Methods: This study is a phase I, multicenter, open-label, single arm study to evaluate the safety and efficacy of neoadjuvant nivolumab monotherapy in patients with resectable GC (stage I or II [cT2 or more advanced for both], or stage III) before standard surgery. Nivolumab 240 mg was administered twice every two weeks. The primary endpoint is safety. Efficacy endpoints include major pathological response (MPR) defined as residual disease < 10% and the response of primary lesion, and surgical endpoints include proportion of patients undergoing surgery with curative intent and R0 resection rate. Biomarkers such as PD-L1 expression and MSI status are also evaluated. Results: From November 2018 to December 2019, 31 GC patients were enrolled into this study. The median age was 69 years (range, 44-84) and 21 patients (67.7%) were men. According to UICC 8th, clinical stage was stage I in 7 patients (22.6%), stage IIA in 0 patients (0%), stage IIB in 14 patients (45.2%), and stage III in 10 patients (32.3%). MSI status was high in 7 patients (22.6%), low in 4 patients (12.9%), and stable in 20 patients (64.5%). Treatment-related adverse events (TRAEs) occurred in 7 patients (22.6%). The most frequent TRAE was rash which occurred in 2 patients (6.5%); the other TRAEs occurred in 1 patient each. Asymptomatic lipase increased was the only grade 3 TRAE; the other TRAEs were all grade 1 or 2 with no new safety signal. All enrolled patients completed 2 doses of nivolumab. Five patients (16.1%) had MPRs, of whom 1 patient had pathological complete response (pCR). Four of 5 MPRs, 1 pCR included, was observed in 7 MSI-H patients (57.1%) and the remaining case of MPR was observed among 20 MSS patients (5%), whereas no MPRs was achieved in 4 MSI-L patients. Among the 31 patients, 30 patients underwent surgery. The remaining 1 patient discontinued the study before surgery due to disease progression. A total of 27 patients (90%) had R0 resection. Conclusions: Neoadjuvant nivolumab monotherapy showed acceptable safety profile and antitumor activity in patients with resectable GC. Recurrence free survival and overall survival in these patients are under follow-up. Clinical trial information: JapicCTI-183895. Clinical trial information: JapicCTI-183895.