TiFFANY study: A multicenter phase II basket-type clinical trial to evaluate efficacy and safety of pan-FGFR inhibitor TAS-120 for advanced solid malignancies with FGFR alterations identified by circulating tumor DNA.

person Tomoko Jogo Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa, Japan info_outline Tomoko Jogo, Yoshiaki Nakamura, Yoshito Komatsu, Ken Kato, Eiji Shinozaki, Hideaki Bando, Takeshi Kato, Tomohiro Nishina, Taito Esaki, Satoshi Fujii, Mitsuko Suzuki, Nozomu Fuse, Akihiro Sato, Shogo Nomura, Martina Lefterova, Justin Odegaard, Hiromichi Ebi, Takayuki Yoshino

Authors person Tomoko Jogo Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa, Japan info_outline Tomoko Jogo, Yoshiaki Nakamura, Yoshito Komatsu, Ken Kato, Eiji Shinozaki, Hideaki Bando, Takeshi Kato, Tomohiro Nishina, Taito Esaki, Satoshi Fujii, Mitsuko Suzuki, Nozomu Fuse, Akihiro Sato, Shogo Nomura, Martina Lefterova, Justin Odegaard, Hiromichi Ebi, Takayuki Yoshino Organizations Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa, Japan, Department of Gastroenterology and Hepatology, Hokkaido University Hospital, Sapporo, Japan, Department of Gastrointestinal Medical Oncology, National Cancer Center Hospital, Tokyo, Japan, Department of Gastroenterology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan, Aichi Cancer Center Hospital, Nagoya, Japan, 6.Department of Surgery, National Hospital Organization Osaka National Hospital, Amagasaki, Japan, National Hospital Organization Shikoku Cancer Center, Matsuyama, Japan, Department of Gastrointestinal and Medical Oncology, National Kyushu Cancer Center, Fukuoka, Japan, National Cancer Center, EPOC, Chiba, Japan, Clinical Research Support Office, National Cancer Center Hospital East, Kashiwa, Japan, National Cancer Center, Kashiwa, Japan, Guardant Health, Redwood City, CA, Lifecode, San Francisco, CA, Division of Molecular Therapeutics, Aichi Cancer Center Research Institute/ Precision Medicine Center, Aichi Cancer Center, Nagoya, Japan, National Cancer Center Hospital East, Kashiwa, Japan Abstract Disclosures Research Funding Other Government Agency Background: Approximately 7% of advanced solid malignancies have FGFR gene alterations. However, standard treatment for FGFR -altered malignancies has not been established. Moreover, circulating tumor DNA (ctDNA) analysis has a potential to accurately identify FGFR alterations by assessing spatial and temporal intratumoral heterogeneity, which have shown to be associated with a poor prognosis and resistance to anti-cancer therapy. Methods: We are conducting an investigator-initiated multicenter phase II basket-type trial to investigate efficacy and safety of TAS-120, a highly selective covalent pan-FGFR inhibitor, for the patients with advanced solid malignancies with FGFR alterations identified by ctDNA analysis as a part of the Nationwide Cancer Genome Screening Project (GOZILA study, UMIN000029315). Eligibility criteria include histologically confirmed unresectable advanced or recurrent solid tumors regardless of histology of origin; ECOG PS of 0 or 1; refractory or intolerant to the standard therapies; and clonal FGFR alterations ( FGFR1-3 gain-of-function mutations, FGFR1,2 amplifications and FGFR2,3 fusions) identified by a 73-gene sequencing ctDNA panel (Guardant360). Enrolled patients will receive TAS-120 20 mg once daily, orally, in a 21 day-cycle. The primary endpoint is to clarify objective response rate (ORR) assessed by investigators per RECIST v1.1. The secondary endpoints are to evaluate progression-free survival, duration of response, time to treatment failure, disease control rate, overall survival, ORR by central determination, and incidence of adverse events. Target sample size is determined as 26 to test the null hypothesis of ORR as 5% with one-sided alpha level of 2.5% and power of 80% to detect an expected value of ORR as 25%. Furthermore, tumor tissue and ctDNA will be serially collected and analyzed to investigate the resistance mechanisms and provide clinically meaningful biomarker which may be used for identifying and implementing treatment changes. Clinical trial information: 194624.