Efficacy and final safety analysis of pre- and co-administration of nivolumab (Nivo) with concurrent chemoradiation (CCRT) followed by Nivo maintenance therapy in patients (pts) with locally advanced cervical carcinoma (LACvCa): Results from the phase I trial, GOTIC-018.
Authors: Nakamura Kazuto , Yabuno Akira , Satoh Toyomi , Fujiwara Hiroyuki , Kurosaki Akira , Yamashita Soichi , Misumi Toshihiro , Noda Shin-ei , Hasegawa Kosei 
Published: June 2023

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Background: LACvCa is associated with a poor prognosis, and CCRT is the standard treatment for LACvCa pts. Anti-PD1 monoclonal antibodies are associated with increased survival in recurrent or persistent CVCa pts; thus, Nivo may enhance antitumor immune responses. We previously reported that the addition of pre- and co-administration of Nivo was safe and feasible in the acute phase in pts with LACvCa who were treated with CCRT (GOTIC-018; JMA-IIA00425). Herein, we report the efficacy and final safety of GOTIC-018. Methods: The GOTIC-018 study was a multicenter, multi-cohort phase I study of Nivo plus CCRT in pts with LACvCa. The treatment plan in cohort A was co-administration of Nivo (240 mg/body once every 2 weeks) with CCRT followed by Nivo maintenance therapy for 52 weeks. The treatment plan in cohort B was pre-CCRT (two doses of Nivo before CCRT) followed by co-administration of Nivo with CCRT followed by Nivo maintenance therapy. Efficacy was evaluated using the RECIST v1.1. Tumor biopsies were obtained before treatment in each cohort and after two doses of Nivo in cohort B. Results: 30 pts (15 in each cohort) were enrolled between May 2019 and June 2021. There were one stage IVA, 11 stage IIIB, 16 stage II, and two stage IB2 tumors based on FIGO 2008. 28 squamous cell and 2 adenocarcinomas were included. 27 of the 30 tumors were positive for high-risk HPV, 14 were positive for PD-L1 TPS, and all tumors were microsatellite stable. The median follow-up was 15.2 months. The median number of Nivo cycles was 30 and 32 for cohorts A and B, respectively. 26 pts completed the study protocol, two discontinued Nivo due to AEs, and two withdrew their consent during the maintenance phase. Ten and eight pts in cohorts A and B, respectively, required Nivo interruption. The best overall response rates were 100% and 93.3% in cohorts A and B, respectively. A total of 73.3% of the pts achieved a complete response in each cohort. The 12-months progression-free survival rate was 100% of the evaluable 29 pts for each cohort. The most common grade ≥ 3 AEs were neutropenia (60.0 and 26.7% in cohorts A and B, respectively), followed by diarrhea (13.3 and 26.7%, respectively), and anemia (13.3 and 16.7%, respectively). Grade ≥ 3 irAEs were observed in two (13.3%) and one (6.7%) pts in cohorts A and B, respectively. The most common grade ≥ 3 irAEs were increased serum lipase levels in two pts. In addition, 6 of the 12 tumors that were PD-L1 TPS negative turned positive after two doses of Nivo in cohort B. Conclusions: The addition of pre- and co-administration of Nivo followed by Nivo maintenance therapy appears safe and shows encouraging efficacy in pts with LACvCa treated with CCRT. Pre-CCRT administration of Nivo may affect the tumor microenvironment. Clinical trial information: JMA-IIA00425 .