GOTIC-018: Phase I, open-label, multicenter study to assess the safety of pre- and co-administration of ONO-4538 (nivolumab) with concurrent chemoradiation (CCRT) in patients (pts) with locally advanced cervical carcinoma (LACvCa).

5529 Background: LACvCa has a poor prognosis. CCRT is the standard treatment for LACvCa, and the 5-year survival rate is estimated at around 60%. Nivolumab (Nivo), an anti-PD1 monoclonal antibody, showed clinical activity in recurrent or persistent CvCa pts. Nivo may enhance antitumor immune responses induced by CCRT. The safety and feasibility of Nivo plus CCRT for LACvCa pts has not yet been reported. We report data from a phase I trial evaluating safety and feasibility of pre- and co-administration of Nivo with CCRT in pts with LACvCa (GOTIC-018; JMA-IIA00425). Methods: The treatment plan in cohort A is co-administration of Nivo (240mg/body once every 2 weeks) with CCRT followed by maintenance therapy with Nivo. The treatment plan in cohort B is pre- (two doses of Nivo before CCRT) and then co-administration of Nivo with CCRT followed by Nivo maintenance. The CCRT regimen includes 4 or more cycles of cisplatin (40 mg/m2 weekly) and external beam radiotherapy (EBRT) followed by brachytherapy. The Nivo maintenance therapy was scheduled for 52 weeks after completion of CCRT. The primary objective is the rate of Grade≧3 adverse events (AEs) during the acute phase, which is defined as 90 days from the start date of EBRT. Secondary objectives include the incidence of dose limiting toxicity (DLT) and progression-free survival. Results: A total of 30 patients, 15 patients in each cohort, was enrolled in this study. This report is a safety evaluation in the acute phase of the study. There were 1 stage IVA, 11 stage IIIB, 16 stage II and 2 stage IB tumors based on FIGO 2009. 28 squamous cell and 2 adeno/adenosquamous carcinomas were included. No DLT was observed in the first 6 DLT-evaluable pts in each cohort. All 30 patients completed planned EBRT and brachytherapy. 2 and 0 patients required a break from EBRT in cohort A and B, respectively. The median cycles of cisplatin administration was 5 and 6 in cohort A and B, respectively. 2 and 0 patient required cisplatin dose reduction in cohort A and B, respectively. 1 patient required cisplatin discontinuation in each cohort. The median cycles of Nivo administration were 6 and 9 in cohort A and B, respectively. 1 patient required Nivo discontinuation due to AEs in each cohort. All patients experienced Grade≧3 AEs. Most common Grade≧3 AEs were neutropenia (60.0 and 26.7% in cohort A and B, respectively), anemia (13.3 and 16.7%) and diarrhea (13.3 and 26.7%). In cohort B, no patients required delay in starting CCRT due to the AEs related to pre-administration of Nivo, and no patients had disease progression before starting CCRT. Conclusions: No DLT was reported during the acute phase in both cohort A and B, and no new safety signals were observed. Addition of pre-and co- administration of Nivo appears safe and feasible in patients with LACvCa treated with CCRT. Clinical trial information: JMA-IIA00425.