1532P - Phase Ib study of futibatinib plus pembrolizumab in patients with esophageal carcinoma: Updated results of antitumor activity and tolerability results in combination with chemotherapy

Background

Combination therapy using FGFR inhibitors and Immune checkpoint inhibitors (ICIs) are being explored as a novel strategy for cancer patients (pts). Previously, we reported the preliminary antitumor activity of irreversible FGFR inhibitor futibatinib plus pembrolizumab in pts with advanced (adv) or metastatic esophageal carcinoma (EC). Here, updated results and tolerability in combination with chemotherapy are presented.

Methods

Pts who are ICI naïve (Cohort A) or ICI refractory (Cohort B) for adv or metastatic EC who have received at least one prior therapy with a fluorouracil and platinum-based drug were administrated with futibatinib plus pembrolizumab. In addition, pts who have not received prior treatment with any systemic chemotherapy received futibatinib 20 mg once daily (QD) plus pembrolizumab 200 mg, fluorouracil 800mg/m² on days 1-5 and cisplatin 80mg/m² every 3weeks in Cohort D. Primary endpoint was overall response rate (ORR) in Cohort A and B, and dose-limiting toxicity (DLT) in Cohort D.

Results

As of March 15, 2023, 31 pts (Cohort A), 50 pts (Cohort B) and 11 pts (Cohort D) were enrolled. As results of the analysis for the cut-off data, confirmed partial responses (PRs) were observed in 11 pts in Cohort A; ORR was 39% with DCR of 75%. In Cohort B, confirmed PRs were observed in 3 pts; ORR was 6% with DCR of 57%. DLT was observed in one pt (Grade 3, Stomatitis) in Cohort D and the RD of futibatinib in combination with pembrolizumab and chemotherapy was determined as 20 mg QD. In Cohort D, most common TRAEs (N=11; all grade, grade ≥3) were hyperphosphatemia (82%, 0%) and stomatitis (82%, 9.1%). Of the 8 pts evaluated for efficacy in Cohort D, confirmed PRs and unconfirmed PRs were observed in 2 pts and 5 pts (5 pts are ongoing), respectively.

Conclusions

Futibatinib plus pembrolizumab showed encouraging antitumor activity in ICIs naïve adv or metastatic EC pts. Futibatinib plus pembrolizumab and chemotherapy showed no new safety signals and manageable safety profile, with promising antitumor activity in pts with adv or metastatic EC who have not received prior treatment with systemic chemotherapy.

Clinical trial identification

jRCT2080224975.

Editorial acknowledgement

Legal entity responsible for the study

Taiho Pharmaceutical Co., Ltd.

Funding

Taiho Pharmaceutical Co., Ltd., Merck & Co., Inc.

Disclosure

S. Yamamoto: Financial Interests, Personal and Institutional, Principal Investigator, Speaker's Bureau: MSD; Financial Interests, Personal, Speaker’s Bureau: Ono, Bristol Myers Squibb, Taiho; Financial Interests, Personal, Writing Engagement: M3; Financial Interests, Personal, Expert Testimony: Hokuto. K. Muro: Financial Interests, Personal, Advisory Board: Amgen, AstraZeneca, Ono, Chugai; Financial Interests, Personal, Invited Speaker: Eli Lilly, Ono, Daiichi Sankyo, Taiho, Bristol Myers Squibb, Takeda; Financial Interests, Institutional, Research Grant, Including local PI as role: Astellas, Amgen, Sanofi, Daiichi Sankyo, Taiho, MSD, Pfizer, Merck Biopharma, Eisai, Ono, Novartis; Financial Interests, Personal, Steering Committee Member: Chugai, AstraZeneca, Amgen; Non-Financial Interests, Principal Investigator: Takeda. K. Nishino: Financial Interests, Personal, Invited Speaker: Ono Pharmaceutical Co., Ltd., NSD, Amgen, Janssen Pharmaceutical K.K., Novartis Pharmaceuticals, Eli Lilly Japan, Takeda Pharmaceutical Co., Ltd., Chugai pharmaceutical, Nippon Boehringer Ingelheim, Nippon Kayaku; Financial Interests, Institutional, Other, Research grant: Ono Pharmaceutical Co., Ltd., Taiho Pharmaceutical Co., Ltd., MSD, AbbVie, Daiichi Sankyo Company, Ltd., Amgen, Sanofi K.K., Janssen Pharmaceutical K.K., Novartis Pharmaceuticals, Pfizer, Eli Lilly, Merck Biopharma Co., Ltd., Takeda Pharmaceutical Co., Ltd., Chugai pharmaceutical, Merus, AstraZeneca; Financial Interests, Institutional, Other, Research grant: Eisai Co., Ltd.; Financial Interests, Personal, Invited Speaker, Advisory Board: Pfizer; Financial Interests, Personal, Invited Speaker, Advisory Board: Merck Biopharma Co., Ltd., AstraZeneca. H. Kawakami: Financial Interests, Personal, Invited Speaker: Bristol Myers Squibb Co. Ltd., Ono Pharmaceutical Co. Ltd, Daiichi Sankyo Co. Ltd., Bayer Yakuhin Ltd, Eli Lilly Japan K.K., MSD K.K., Chugai Pharmaceutical Co. Ltd., Merck Biopharma Co., Ltd., Takeda Pharmaceutical Co. Ltd., Yakult Pharmaceutical Industry, Teijin Pharma Ltd., Taiho Pharmaceutical Co. Ltd.; Financial Interests, Personal, Advisory Board: Daiichi Sankyo Co. Ltd.; Financial Interests, Personal, Other, Lecture: GSKK.K, Otsuka Pharmaceutical Co., Ltd.; Financial Interests, Institutional, Research Grant, Investigator-Initiated Trial: Bristol Myers Squibb Co. Ltd.; Financial Interests, Institutional, Research Grant: Taiho Pharmaceutical Co. Ltd, Eisai Co., Ltd., Kobayashi Pharmaceutical Co. Ltd., Parexel International Corp., PRA Health Sciences, EPS Corporation., Kissei Pharmaceutical Co., Ltd., EPS International Co., Ltd,., MSD K.K., Ono Pharmaceutical Co., Ltd., PPD-SNBL K.K, SymBio Pharmaceuticals Limited., IQVIA Services Japan K.K., Syneos Health Clinical K.K., Nippon Kayaku Co., Ltd., EP-CRSU Co., Ltd., Mebix, Inc., Bristol Myers Squibb K.K., Janssen Pharmaceutical K.K., Eisai Co., Ltd., AstraZeneca K.K., Mochida Pharmaceutical Co., Ltd., Covance Japan Inc., Japan Clinical Research Operations, Chugai Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., GSK K.K., Sanofi K.K., Nippon Boehringer Ingelheim Co., Ltd., Sysmex Corporation, Novartis Pharma K.K., Otsuka Pharmaceutical Co., Ltd., SRL, Inc., Daiichi Sankyo Co., Ltd., Amgen Inc., Medical Research Support, Eli Lilly Japan K.K. T. Kojima: Financial Interests, Institutional, Principal Investigator: BeiGene Ltd., MSD K.K., Amgen Inc., Shionogi & Co., Ltd., Ono Pharmaceutical Co., Ltd., Chugai Pharmaceutical CO.,LTD., Taiho Pharmaceutical Co., Ltd., Parexel International; Financial Interests, Institutional, Research Grant: EPS Corporation.; Financial Interests, Personal, Invited Speaker: Bristol Myers Squibb, Ono Pharmaceutical Co., Ltd., Covidien Japan, Inc., MSD K.K., Taiho Pharmaceutical Co., Ltd.; Financial Interests, Personal, Writing Engagement: MSD K.K.; Financial Interests, Personal, Advisory Board: Merck Biopharma Co., Ltd. N. Machida: Financial Interests, Personal, Speaker’s Bureau: MSD, Ono Pharmaceutical Co., Ltd., Bristol Myers Squibb, Daiichi Sankyo, Inc., Taiho Pharmaceutical Co., Ltd., Yakult, Eli Lilly Japan K.K., Merck Biopharma Japan, Nichi-Iko. H. Hirai: Other, Personal, Full or part-time Employment: Taiho Pharmaceutical Co. Ltd.; Financial Interests, Personal, Stocks/Shares: Otsuka HD. M. Chisamore: Other, Personal, Full or part-time Employment: Merck & Co., Inc; Financial Interests, Personal, Stocks/Shares: Merck & Co., Inc. K. Chin: Financial Interests, Personal, Speaker’s Bureau: Taiho Pharma, Ono Pharmaceutical Co, Ltd., Bristol Myers Squibb, Chugai Pharmaceutical Co., Ltd., Merck & Co., Inc. All other authors have declared no conflicts of interest.