128P - Clinical update with plasma and tumour-based genomic analyses in expansion part of phase I study of selective FGFR inhibitor E7090

Background

The first-in-human phase I study of E7090 consists of dose-escalation (Part 1) and expansion (Part 2) cohorts, which has been conducted in Japan. The interim analysis results of Part 2, as of 31 July 2019, were reported (ASCO-GI 2020 #538). The interim analysis indicated that E7090 had a manageable safety profile and the promising clinical activity in cholangiocarcinoma subjects with FGFR2 rearrangements. In this study, we analyzed tumor tissue and plasma samples with NGS panels to assess baseline tumor gene characteristics and evolution of the ctDNA profile during E7090 treatment.

Methods

In part 2, subjects with cholangiocarcinoma harboring FGFR2 gene rearrangements (cholangiocarcinoma [CCA] cohort) and gastric cancer harboring FGFR2 gene amplification or FGFR2 protein high expression (GC cohort) were enrolled. Archival tumor tissue samples were analyzed with PGDx elio tissue complete NGS panel (PGDx; Personal Genome Diagnostics, Inc.). Plasma sample was collected at pre-treatment, every day 1 of odd cycle on-treatment and at discontinuation visit for ctDNA analysis with PGDx elio plasma resolve NGS panel.

Results

As of cutoff date, 3 June 2020, 6 subjects harboring FGFR2 rearrangements identified with break-apart fluorescence in situ hybridization were enrolled in the CCA cohort. Among six tumor tissue samples, one was failed in quality-check of NGS assay. Fusion gene partner in FGFR2 rearrangements was identified in 4 of the 5 tumor tissues as BICC1, CCDC6, POC1B, and SLMAP (n=1, each). FGFR2 rearrangements were also detected in baseline blood samples from 3 of the 6 subjects. In those three cases, the number of mutant reads for FGFR2 rearrangements in ctDNA assay decreased during treatment. ctDNA for FGFR2 (L617F, M537I) were detected in blood from 2 subjects at discontinuation visit. The updated efficacy and safety results in Part 2 will also be presented as of a new cutoff date.

Conclusions

The NGS assay illuminated FGFR2 fusion partners in archival tumor tissues. Besides, ctDNA analysis indicated ctDNA for FGFR2 rearrangements were decreased during E7090 treatments, and the potential clonal changes occurred as detections of ctDNA with FGFR2 mutations.

Clinical trial identification

NCT02275910.

Editorial acknowledgement

Legal entity responsible for the study

Eisai.

Funding

Eisai.

Disclosure

C. Morizane: Honoraria (self): MSD K.K., Yakult Honsha, Novartis, Eisai, Teijin Pharma, Taiho Pharmaceutical; Research grant/Funding (institution): Yakult Honsha, Eisai, Taiho Pharmaceutical, Merck Biopharma, AstraZeneca, J-Pharma; Advisory/Consultancy: MSD K.K., AbbVie, Novartis, AstraZeneca,. M. Ueno: Honoraria (self): Taiho Pharmaceutical, Yakult Honsha, AstraZeneca, Ono Pharmaceutical, Merck Biopharma, MSD; Research grant/Funding (institution): Taiho Pharmaceutical, Daiichi Sankyo, Eisai, AstraZeneca, Ono Pharmaceutical, MSD, Merck Biopharma, Dainippon Sumitomo Pharma, Incyte, Yakult Honsha, Astellas. T. Ioka: Honoraria (self): Taiho Pharmaceutical, Chugai Pharma, Daiichi Sankyo, Yakult Honsha, Otsuka; Advisory/Consultancy: Taiho Pharmaceutical, Otsuka, Shire, Daiichi Sankyo; Research grant/Funding (institution): AstraZeneca, Dainippon Sumitomo Pharma, Baxalta/Shire, Eisai, Taiho Pharmaceutical, Taiho Pharmaceutical, Incyte, Takara Bio; Research grant/Funding (self): Taiho Pharmaceutical. M. Tajika: Speaker Bureau/Expert testimony: EA Pharma Co., Ltd., Olympus. M. Ikeda: Research grant/Funding (institution): Aslan Pharmaceuticals; Honoraria (self): Astellas; Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Bayer; Research grant/Funding (institution): Bristol-Myers Sqiibb; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Chugai Pharmaceutical; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Eisai; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Eli Lilly Japan; Research grant/Funding (institution): J-Pharma; Research grant/Funding (institution): Merck Serono; Advisory/Consultancy: Micron; Research grant/Funding (institution): MSD; Honoraria (self), Research grant/Funding (institution): Yakult; Honoraria (self), Advisory/Consultancy: Nihon Seriver; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Novartis Pharma; Advisory/Consultancy, Research grant/Funding (institution): Ono Pharmaceutical; Honoraria (self): Mylan, Otsuka Pharmaceutical; Honoraria (self): Pfizer; Honoraria (self): Taiho Pharmaceutical, Teijin Pharma; Advisory/Consultancy: Takeda. K. Yamaguchi: Honoraria (institution), Speaker Bureau/Expert testimony: Daiichi Sankyo; Honoraria (institution), Speaker Bureau/Expert testimony: Taiho Pharmaceutical; Honoraria (institution), Speaker Bureau/Expert testimony: Chugai Pharm; Speaker Bureau/Expert testimony: Bristol-Myers Squibb Japan; Honoraria (institution), Speaker Bureau/Expert testimony: Ono Pharmaceutical; Speaker Bureau/Expert testimony: Takeda; Honoraria (institution), Speaker Bureau/Expert testimony: Lilly; Honoraria (institution), Speaker Bureau/Expert testimony: Sanofi; Honoraria (institution): MSD oncology; Honoraria (institution): Dainippon Sumitomo Pharma; Honoraria (institution): Gilead Sciences; Honoraria (institution): Boehringer Ingelheim; Honoraria (institution): Eisai; Honoraria (institution): Yakult Honsha. H. Hara: Advisory/Consultancy: Lilly, MSD, Ono: Honoraria (institution): Bayer, Bristol-Myers Squibb, Chugai, Daiichi Sankyo, Kyowa Hakko Kirin, Lilly, Merck Biopharma, MSD, Ono, Sanofi, Taiho, Takeda and Yakult; Research grant/Funding (institution): Astellas, AstraZeneca, BeiGene, Boehringer Ingelheim, Chugai, Daiichi Sankyo, Dainippon Sumitomo, Eisai, Incyte, LSK BioPharma, Merck Biopharma, MSD, Ono, Pfizer, Taiho. A. Miyamoto: Research grant/Funding (institution): Eisai. S. Iwasa: Research grant/Funding (institution): Eisai, BMS, Daiichi-Sankyo, Ono, Bayer, Pfizer, Astellas; Honoraria (self): BMS, Ono, Chugai, Taiho. M. Muto: Research grant/Funding (institution): Eisai. T. Takashima: Honoraria (self): Taiho Pharmaceutical Co., Ltd; Honoraria (self): Eisai Co., Ltd.; Honoraria (self): Chugai Pharmaceutical Co., Ltd.; Honoraria (self): Eli Lilly Japan K.K.; Honoraria (self): Pfizer Japan Inc.; Honoraria (self): Novartis Pharma K.K.; Honoraria (self): Kyowa Hakko Kirin Co., Ltd.; Honoraria (self): Daiichi-Sankyo K.K. K. Minashi: Research grant/Funding (institution): Ono Pharmaceutical Co., Ltd; Research grant/Funding (institution): Daiichi Sankyo Company, Limited. Y. Komatsu: Honoraria (self), Speaker Bureau/Expert testimony, Research grant/Funding (institution): Daiichi-Sankyo, Yakult, Chugai, Taiho, Lilly, Sanofi, Ono, Nipro, Asahikasei, Nihonkayaku, Takeda; Research grant/Funding (institution): Eisai, MSD; Honoraria (self), Research grant/Funding (self): Bayer; Honoraria (self): Kyowa Kirin, Merck Biopharma, Bristol-Myers Squibb, Shire Japan, Novartis Pharma, Pfizer, Mitsubishi Tanabe, Otsuka; Research grant/Funding (self): A2 Healthcare Corp., Astellas Pharma, Dainippon Sumitomo Pharma, NanoCarrier, Parexel International Corporation, IQVIA Inc., Syneos Health Clinical, Sysmex Corporation. T. Nishina: Honoraria (self), Research grant/Funding (institution): Taiho Pharmaceutical; Honoraria (self), Research grant/Funding (institution): Chugai Pharma; Honoraria (self), Research grant/Funding (institution): Merck biopharma; Honoraria (self), Research grant/Funding (institution): Bristol-Myers Suibb; Honoraria (self), Research grant/Funding (institution): Ono Pharmaceutical; Research grant/Funding (institution): MSD; Research grant/Funding (institution): AstraZeneca; Research grant/Funding (institution): Daiichi Sankyo; Research grant/Funding (institution): Dainippon Sumitomo; Research grant/Funding (institution): Eisai; Honoraria (self): Nihonkayaku; Honoraria (self): Yaklut Honsya. T. Nakajima: Honoraria (self): Mochida Pharmaceutical, Celltrion Healthcare Japan, Merck Serono Co., Sawai Pharmaceutical Co., Bayer Yakuhin, Bristol-Myers Squibb, Teijin Pharma, Pfizer Japan Inc., Novartis Japan, Yakult Honsha Co., Nipro Co.; Honoraria (self), Research grant/Funding (institution): Taiho Pharmaceutical Co., Chugai Pharmaceutical Co., Takeda Pharmaceutical Co., Sanofi K.K., Daiichi Sankyo Co., Eli Lilly Japan K.K., Nippon Kayaku Co., Ono Pharmaceutical Co., MSD K.K.; Research grant/Funding (institution): Astellas Pharma Inc., Sumitomo Dainippon Pharma Co., Eisai Co., Solasia Pharma K.K. T. Sahara: Full/Part-time employment: Eisai. S. Funasaka: Full/Part-time employment: Eisai. M. Yashiro: Research grant/Funding (self): Eisai Co., Ltd.; Research grant/Funding (self): Daiichi Sankyo Co., Ltd.; Research grant/Funding (self): Chiome Bioscience Inc.; Research grant/Funding (self): Five Prime Therapeutics, Inc. J. Furuse: Honoraria (self): Eisai, Bayer Yakuhin, Taiho Pharmaceutical, Ono Pharmaceutical, Novartis, Yakult Honsha, Teijin Pharma, Shionogi, EA Pharma, Eli Lilly Japan, Takeda, Chugai Pharma, Fujifilm, Mochida Pharmaceutical, Nihon Servier, Sanofi, Fujifilm Toyama Chemical, Nobel p; Research grant/Funding (institution): Eisai, Fujifilm, Ono Pharmaceutical, Yakult Honsha, Taiho Pharmaceutical, Eli Lilly Japan, Astellas Pharma, AstraZeneca, AbbVie, Shire, Merck Serono, Takara Bio, Chugai Pharma, Bayer Yakuhin, Otsuka, Novartis, MSD, Sumitomo Dainippon, J-Pharma. All other authors have declared no conflicts of interest.