Abstract 1799TiP
Background
The efficacy of nivolumab monotherapy has demonstrated survival benefit for patients with metastatic and recurrent esophageal squamous cell carcinoma in ATTRACTION-3 study. However, about only 20% of the patients respond to nivolumab, raising the necessity of its predictive biomarkers. Recent studies showed that gut microbiome as an important regulator of immunity, with the potential to modulate responses to immune check point inhibitors (ICIs). However, the specific functions and molecular mechanisms of each component of the complex gut microbiome remain largely unknown. Moreover, reported bacteria are different among studies. It implies that the immune-modulating effects of the gut microbiota are different according to race, geography, foods and cancer types. Furthermore, some species of oral bacteria was reported to development and presence of the intratumor bacteria was associated with poor prognosis of esophageal cancer.
Trial design
To evaluate the efficacy and the safety of nivolumab monotherapy for patients with metastatic and recurrent esophageal cancer and explore the utility of oral and gut microbiome as a potential biomarker, HGCSG2002 study has started as multicenter observational biomarker study. The patients with metastatic or recurrent esophageal squamous cell carcinoma who receive nivolumab monotherapy are eligible for this study. Nivolumab 240 mg is administered intravenously every 2 weeks. Samples of saliva and feces are collected at three point; before the initial treatment, 4 weeks after the first administration and after the finish of nivolumab treatment. The analysis with 16S rRNA gene sequences is planned to investigate bacterial diversity and taxonomic profile. The primary endpoint is overall survival, and the secondary endpoints are progression-free survival, safety and association between oral and gut microbiome and clinical outcome. A total of 25 cases are planned for registration within 2 years. This study was approved by the institutional review board of Hokkaido University Hospital (approval number: 020-0224). This study is registered with UMIN registration number: UMIN000043208.
Clinical trial identification
UMIN000043208.
Editorial acknowledgement
Legal entity responsible for the study
Hokkaido Gastrointestinal Cancer Study Group.
Funding
Ono Pharmaceutical Co., Ltd.
Disclosure
K. Harada: Financial Interests, Personal, Invited Speaker: Ono Pharmaceutical Co., Ltd.; Financial Interests, Personal, Invited Speaker: Chugai Pharmaceutical Co., Ltd.; Financial Interests, Personal, Invited Speaker: Taiho Pharmaceutical Co., Ltd.; Financial Interests, Personal, Invited Speaker: Takeda Pharmaceutical Company Limited; Financial Interests, Personal, Invited Speaker: Nippon Kayaku Co.,Ltd.; Financial Interests, Personal, Invited Speaker: Bayer Yakuhin, Ltd. S. Yuki: Financial Interests, Personal, Invited Speaker: Chugai Pharmaceutical Co., Ltd.; Financial Interests, Personal, Invited Speaker: Eli Lilly K.K.; Financial Interests, Personal, Invited Speaker: Takeda Pharmaceutical Co., Ltd.; Financial Interests, Personal, Invited Speaker: Bayer Yakuhin, Ltd; Financial Interests, Personal, Invited Speaker: Bristol-Myers Squibb Co., Ltd.; Financial Interests, Personal, Invited Speaker: Taiho Pharmaceutical Co., Ltd.; Financial Interests, Personal, Invited Speaker: MSD K.K.; Financial Interests, Personal, Invited Speaker: Ono Pharmaceutical Co., Ltd.; Financial Interests, Personal, Invited Speaker: Medical & Biological Laboratories Co., Ltd.; Financial Interests, Personal, Invited Speaker: Yakult Honsha Co., Ltd.; Financial Interests, Personal, Invited Speaker: Merck Biopharma Co., Ltd.; Financial Interests, Personal, Invited Speaker: Sanofi K.K.. Y. Tsuji: Financial Interests, Personal, Invited Speaker: Daiichi Sankyo Co. Ltd.; Financial Interests, Personal, Invited Speaker: Ono Pharmaceutical Co. Ltd.; Financial Interests, Personal, Invited Speaker: Asahi Kasei Pharma Co. Ltd.; Financial Interests, Personal, Invited Speaker: Sawai Pharmaceutical Co. Ltd.; Financial Interests, Personal, Invited Speaker: Eli Lilly Japan Co. Ltd.; Financial Interests, Personal, Invited Speaker: Merck Biopharma Co. Ltd.; Financial Interests, Personal, Invited Speaker: Nippon Kayaku Co. Ltd.; Financial Interests, Personal, Invited Speaker: Taiho Pharmaceutical Co. Ltd.; Financial Interests, Personal, Invited Speaker: Bayer Co. Ltd. I. Yokota: Financial Interests, Personal, Research Grant: Japan Society for the Promotion of Science Kakenhi; Financial Interests, Personal, Research Grant: Health, Labour and Welfare Policy Research Grants; Financial Interests, Personal, Invited Speaker: Chugai Pharmaceutical Co,; Financial Interests, Personal, Invited Speaker: AstraZeneca plt; Financial Interests, Personal, Invited Speaker: Japan Tabacco Pharamaceutical Division; Financial Interests, Personal, Invited Speaker: Nippon Shinyaku Co. N. Sakamoto: Financial Interests, Personal, Invited Speaker: Gilead Sciences; Financial Interests, Personal, Invited Speaker: Chugai Parm; Financial Interests, Personal, Invited Speaker: Bayer AG; Financial Interests, Personal, Invited Speaker: Otsuka Pharm; Financial Interests, Personal, Invited Speaker: Daiichi Sankyo; Financial Interests, Personal, Invited Speaker: Astellas Pharma; Financial Interests, Personal, Invited Speaker: Takeda; Financial Interests, Personal, Invited Speaker: Eisai; Financial Interests, Personal, Research Grant: Gilead Sciences; Financial Interests, Personal, Research Grant: Eisai; Financial Interests, Personal, Research Grant: MSD; Financial Interests, Personal, Research Grant: Otsuka Pharm; Financial Interests, Personal, Research Grant: AbbVie; Financial Interests, Personal, Research Grant: Asuka Pharm. Y. Sakata: Financial Interests, Personal, Invited Speaker: Yakult Honsha; Financial Interests, Personal, Invited Speaker: Taiho Pharmaceutical; Financial Interests, Personal, Invited Speaker: Eli Lilly; Financial Interests, Personal, Invited Speaker: Daiichi Sankyo Co. Ltd.; Financial Interests, Personal, Invited Speaker: BMS Co; Financial Interests, Personal, Stocks/Shares: Delt-fly pharm. Y. Komatsu: Financial Interests, Personal, Research Grant: MSD; Financial Interests, Personal, Research Grant: JFMC; Financial Interests, Personal, Research Grant: NanoCarrier; Financial Interests, Personal, Research Grant: Yakult; Financial Interests, Personal, Research Grant: Mediscience; Financial Interests, Personal, Research Grant: National cancer center; Financial Interests, Personal, Research Grant: ONO; Financial Interests, Personal, Research Grant: Taiho; Financial Interests, Personal, Research Grant: Daiichi Sankyo; Financial Interests, Personal, Research Grant: IQVIA; Financial Interests, Personal, Research Grant: Chugai; Financial Interests, Personal, Invited Speaker: Ono; Financial Interests, Personal, Invited Speaker: Taiho; Financial Interests, Personal, Invited Speaker: Chugai; Financial Interests, Personal, Invited Speaker: Bayer; Financial Interests, Personal, Invited Speaker: Eli Lilly; Financial Interests, Institutional, Research Grant: Eli Lilly; Financial Interests, Institutional, Research Grant: Nipro. All other authors have declared no conflicts of interest.