Abstract 1383P
Background
Initial results from a phase I dose escalation/expansion (EX) study (JapicCTI-142552) indicated tolerability and preliminary efficacy of futibatinib at doses up to 160 mg thrice weekly (TIW) and 20 mg once daily (QD) in patients (pts) with advanced (adv) solid tumors. Here, updated results from the phase I EX, including activity in pts with gastric cancer (GC), are presented.
Methods
In EX, pts with adv FGF/FGFR-aberrant tumors and no alternative treatment options received futibatinib 56, 80, or 120 mg TIW, or 16 or 20 mg QD. Primary endpoint was antitumor activity in GC and other solid tumors. Secondary objectives included safety and evaluation of activity in GC based on FGFR abnormality.
Results
As of November 26, 2020, 44 pts received futibatinib TIW (N=11) or QD [N=33, (N=31, 20 mg QD)] in the EX cohorts. Most common tumor types were GC (N=20), biliary tract tumors (N=5), and esophageal cancer (N=4). In the QD dosing cohorts (N=33), confirmed partial responses (PRs) were observed in 3 pts with GC and 1 pt with cholangiocarcinoma (CCA); objective response rate (ORR) was 12%. All 3 GC pts with confirmed PRs (tumor shrinkage: 59, 60, and 73%) had FGFR2 amplification (amp) with copy number value (CNV) >10. In the subset of GC pts with FGFR2 amp CNV >10 receiving 20 mg QD (N=9), ORR was 33% with a disease control rate of 44%. The CCA pt with a confirmed PR had an FGFR2 mutation. No PRs were observed in pts receiving futibatinib TIW dosing. Safety profile of futibatinib TIW and QD dosing was consistent with that of previous reports. Most common treatment-related adverse events in pts receiving 20 mg QD (N=31; all; grade ≥3) were hyperphosphatemia (100%; 7%), decreased appetite (42%; 7%), and elevated ALT (19%; 0%) and AST (19%; 3%) levels.
Conclusions
Futibatinib showed antitumor activity with a manageable safety profile in Japanese pts with adv solid tumors. In particular, promising preliminary antitumor activity was observed in pts with adv GC and FGFR2 amp CNV >10, supporting further investigation of futibatinib dosing in pts with GC harboring FGFR2 amp in an ongoing global phase II study (NCT04189445). Further phase II/III studies of futibatinib in pts with CCA and breast cancer are ongoing.
Clinical trial identification
JapicCTI-142552.
Editorial acknowledgement
Legal entity responsible for the study
Taiho Pharmaceutical Co., Ltd.
Funding
Taiho Pharmaceutical Co., Ltd.
Disclosure
Y. Kuboki: Financial Interests, Personal, Invited Speaker: Merck Serono; Financial Interests, Personal, Invited Speaker: Lilly Japan; Financial Interests, Personal, Invited Speaker: Taiho Pharmaceutical; Financial Interests, Personal, Invited Speaker: ONO; Financial Interests, Personal, Invited Speaker: Bayer; Financial Interests, Personal, Invited Speaker: Sanofi; Financial Interests, Personal, Invited Speaker: Bristol-Myers Squibb Japan; Financial Interests, Personal, Advisory Role: Boehringer Ingelheim; Financial Interests, Personal, Advisory Role: Takeda; Financial Interests, Personal, Advisory Role: Amgen; Financial Interests, Institutional, Principal Investigator: Takeda; Financial Interests, Institutional, Principal Investigator: Daiichi Sankyo; Financial Interests, Institutional, Principal Investigator: Amgen; Financial Interests, Institutional, Principal Investigator: Genmab; Financial Interests, Institutional, Principal Investigator: Taiho Pharmaceutical; Financial Interests, Institutional, Principal Investigator: Janssen Oncology; Financial Interests, Institutional, Principal Investigator: AstraZeneca; Financial Interests, Institutional, Principal Investigator: Boehringer Ingelheim; Financial Interests, Institutional, Principal Investigator: GlaxoSmithKline; Financial Interests, Institutional, Principal Investigator: Astellas Pharma; Financial Interests, Institutional, Principal Investigator: Incyte; Financial Interests, Institutional, Principal Investigator: Ono Pharmaceutical; Financial Interests, Institutional, Principal Investigator: Chugai Pharma. K. Shitara: Financial Interests, Personal, Invited Speaker: AbbVie; Financial Interests, Personal, Advisory Board: AbbVie; Financial Interests, Personal, Advisory Board: Amgen; Financial Interests, Personal, Advisory Board: Astellas; Financial Interests, Personal, Advisory Board: Boehringer Ingelheim; Financial Interests, Personal, Advisory Board: Bristol-Myers Squibb; Financial Interests, Personal, Advisory Board: Daiichi Sankyo; Financial Interests, Personal, Advisory Board: GlaxoSmithKline; Financial Interests, Personal, Advisory Board: Lilly; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: ONO Pharmaceutical; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: TAIHO Pharmaceutical; Financial Interests, Personal, Advisory Board: Takeda; Financial Interests, Personal, Invited Speaker: Yakult Honsha; Financial Interests, Institutional, Research Grant: Astellas; Financial Interests, Institutional, Research Grant: CHUGAI Pharmaceutical; Financial Interests, Institutional, Research Grant: Daiici Sankyo; Financial Interests, Institutional, Research Grant: Eisai; Financial Interests, Institutional, Research Grant: Lilly; Financial Interests, Institutional, Research Grant: Medi Science; Financial Interests, Institutional, Research Grant: MSD; Financial Interests, Institutional, Research Grant: ONO Pharmaceutical; Financial Interests, Institutional, Research Grant: Sumitomo Dainippon; Financial Interests, Institutional, Research Grant: TAIHO Pharmaceutical. C. Morizane: Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Invited Speaker: Yakult Honsha; Financial Interests, Personal, Invited Speaker: Teijin Pharma; Financial Interests, Personal, Invited Speaker: Taiho Pharmaceutical; Financial Interests, Personal, Invited Speaker: Eisai; Financial Interests, Personal, Invited Speaker: MSD KK; Financial Interests, Personal, Advisory Board: Yakult Honsha; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: Taiho Pharmaceutical; Financial Interests, Personal, Advisory Board: AbbVie; Financial Interests, Personal, Advisory Board: MSD KK; Financial Interests, Institutional, Research Grant: Eisai; Financial Interests, Institutional, Research Grant: Yakult Honsha; Financial Interests, Institutional, Research Grant: Ono Pharmaceutical; Financial Interests, Institutional, Research Grant: Taiho Pharmaceutical; Financial Interests, Institutional, Research Grant: J-Pharma; Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Institutional, Research Grant: Merck biopharma. T. Kojima: Financial Interests, Institutional, Principal Investigator: Ono Pharmaceutical Co., Ltd.; Financial Interests, Institutional, Principal Investigator: Bristol-Myers Squibb; Financial Interests, Institutional, Principal Investigator: MSD; Financial Interests, Institutional, Principal Investigator: Astellas Amgen BioPharma; Financial Interests, Institutional, Principal Investigator: Chugaiseiyaku; Financial Interests, Institutional, Principal Investigator: Parexel; Financial Interests, Institutional, Principal Investigator: Shionogi; Financial Interests, Personal, Advisory Board: Astellas; Financial Interests, Personal, Advisory Board: Merck Biopharma; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Advisory Board: Bristol-Myers Squibb; Financial Interests, Personal, Invited Speaker: Ono Pharmaceutical Co., Ltd; Financial Interests, Personal, Invited Speaker: Oncolys BioPharma. K. Yoh: Financial Interests, Institutional, Principal Investigator: AstraZeneca; Financial Interests, Institutional, Principal Investigator: Lilly; Financial Interests, Institutional, Principal Investigator: Pfizer; Financial Interests, Institutional, Principal Investigator: Daiichi sankyo; Financial Interests, Institutional, Principal Investigator: AbbVie; Financial Interests, Institutional, Principal Investigator: Taiho; Financial Interests, Institutional, Principal Investigator: Bayer; Financial Interests, Institutional, Principal Investigator: Takeda; Financial Interests, Institutional, Principal Investigator: MSD; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Invited Speaker: Bristol-Myers Squibb; Financial Interests, Personal, Invited Speaker: Chugai; Financial Interests, Personal, Invited Speaker: Daiichi Sankyo; Financial Interests, Personal, Invited Speaker: Janssen; Financial Interests, Personal, Invited Speaker: Lilly; Financial Interests, Personal, Invited Speaker: Taiho; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Invited Speaker: Kyowa kirin; Financial Interests, Personal, Invited Speaker: Boehringer Ingelheim. D. Sakai: Financial Interests, Institutional, Research Grant: Daiichi Sankyo; Financial Interests, Institutional, Research Grant: Lilly Japan; Financial Interests, Institutional, Research Grant: Chugai Pharma; Financial Interests, Institutional, Research Grant: Yakult Honsha; Financial Interests, Institutional, Research Grant: Ono Pharmaceutical; Financial Interests, Institutional, Research Grant: Astellas Pharma; Financial Interests, Institutional, Research Grant: Incyte; Financial Interests, Institutional, Research Grant: Taiho Pharmaceutical; Financial Interests, Institutional, Research Grant: Eisai; Financial Interests, Personal, Speaker’s Bureau: Chugai Pharma. M. Tahara: Financial Interests, Personal, Invited Speaker: Merck Biopharma; Financial Interests, Personal, Advisory Board: Merck Biopharma; Financial Interests, Personal, Invited Speaker: Bristol-Myers Squibb; Financial Interests, Personal, Advisory Board: Bristol-Myers Squibb; Financial Interests, Institutional, Research Grant: Bristol-Myers Squibb; Financial Interests, Personal, Invited Speaker: Eisai; Financial Interests, Personal, Advisory Board: Eisai; Financial Interests, Personal, Invited Speaker: Ono Pharmaceutical; Financial Interests, Personal, Advisory Board: Ono Pharmaceutical; Financial Interests, Institutional, Research Grant: Ono Pharmaceutical; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Institutional, Research Grant: MSD; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: Rakuten Medical; Financial Interests, Institutional, Research Grant: Rakuten Medical; Financial Interests, Personal, Invited Speaker: Bayer; Financial Interests, Personal, Advisory Board: Bayer; Financial Interests, Institutional, Research Grant: Bayer; Financial Interests, Personal, Advisory Board: Lilly; Financial Interests, Institutional, Research Grant: Lilly; Financial Interests, Personal, Advisory Board: LOXO; Financial Interests, Institutional, Research Grant: LOXO; Financial Interests, Institutional, Research Grant: GlaxoSmithKline. H. Hirai: Other, Personal, Full or part-time Employment: Taiho Pharmaceutical. Y. Kurokawa: Financial Interests, Personal, Speaker’s Bureau: Taiho Pharmaceutical; Financial Interests, Institutional, Research Grant: Taiho Pharmaceutical. T. Kato: Financial Interests, Institutional, Research Grant: AbbVie; Financial Interests, Personal and Institutional, Invited Speaker: Amgen; Financial Interests, Personal and Institutional, Advisory Board: Amgen; Financial Interests, Personal and Institutional, Research Grant: Amgen; Financial Interests, Personal and Institutional, Invited Speaker: AstraZeneca; Financial Interests, Personal and Institutional, Advisory Board: AstraZeneca; Financial Interests, Personal and Institutional, Research Grant: AstraZeneca; Financial Interests, Personal and Institutional, Invited Speaker: Chugai; Financial Interests, Personal and Institutional, Research Grant: Chugai; Financial Interests, Personal and Institutional, Invited Speaker: Eli Lilly; Financial Interests, Personal and Institutional, Advisory Board: Eli Lilly; Financial Interests, Personal and Institutional, Research Grant: Eli Lilly; Financial Interests, Personal and Institutional, Invited Speaker: Merck Biopharma; Financial Interests, Personal and Institutional, Advisory Board: Merck Biopharma; Financial Interests, Personal and Institutional, Research Grant: Merck Biopharma; Financial Interests, Personal and Institutional, Invited Speaker: MSD; Financial Interests, Personal and Institutional, Advisory Board: MSD; Financial Interests, Personal and Institutional, Research Grant: MSD; Financial Interests, Personal and Institutional, Invited Speaker: Novartis; Financial Interests, Personal and Institutional, Advisory Board: Novartis; Financial Interests, Personal and Institutional, Research Grant: Novartis; Financial Interests, Personal and Institutional, Invited Speaker: Pfizer; Financial Interests, Personal and Institutional, Advisory Board: Pfizer; Financial Interests, Personal and Institutional, Research Grant: Pfizer; Financial Interests, Personal, Invited Speaker: Daiichi Sankyo; Financial Interests, Personal, Advisory Board: Daiichi Sankyo; Financial Interests, Institutional, Research Grant: Regeneron. T. Doi: Financial Interests, Institutional, Principal Investigator: Lilly; Financial Interests, Institutional, Principal Investigator: MSD; Financial Interests, Institutional, Principal Investigator: Daiichi Sankyo; Financial Interests, Institutional, Principal Investigator: Sumitomo Dainippon; Financial Interests, Institutional, Principal Investigator: Taiho; Financial Interests, Institutional, Principal Investigator: Novartis; Financial Interests, Institutional, Principal Investigator: Merck Serono; Financial Interests, Institutional, Principal Investigator: Janssen; Financial Interests, Institutional, Principal Investigator: Boehringer Ingelheim; Financial Interests, Institutional, Principal Investigator: Pfizer; Financial Interests, Institutional, Principal Investigator: Bristol-Myers Squibb; Financial Interests, Institutional, Principal Investigator: AbbVie; Financial Interests, Institutional, Principal Investigator: Quintiles (IQVIA); Financial Interests, Institutional, Principal Investigator: Eisai; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Advisory Board: Daiichi Sankyo; Financial Interests, Personal, Advisory Board: Amgen; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: Janssen; Financial Interests, Personal, Advisory Board: Boehringer Ingelheim; Financial Interests, Personal, Advisory Board: AbbVie; Financial Interests, Personal, Advisory Board: Bayer; Financial Interests, Personal, Advisory Board: Astellas Pharma; Financial Interests, Personal, Advisory Role: Sumitomo Dainippon; Financial Interests, Personal, Advisory Role: Taiho; Financial Interests, Personal, Advisory Role: Takeda; Financial Interests, Personal, Advisory Role: Chugai Pharma; Financial Interests, Personal, Advisory Role: Rakuten Medical; Financial Interests, Personal, Advisory Role: Otsuka Pharma; Financial Interests, Personal, Advisory Role: Oncolys BioPharma; Financial Interests, Personal, Invited Speaker: Bristol-Myers Squibb; Financial Interests, Personal, Invited Speaker: Ono Pharmaceutical; Financial Interests, Personal, Invited Speaker: Taiho.