Abstract 1241P
Background
Combination therapy using FGFR inhibitors and Immune checkpoint inhibitors (ICIs) are being explored as a novel strategy for cancer patients (pts). Here, we report the safety and tolerability of FGFR inhibitor futibatinib plus pembrolizumab in pts with advanced (adv) or metastatic solid tumors and first results for preliminary antitumor activity in pts with esophageal carcinoma (EC).
Methods
This study consists of Feasibility phase (FP) and Expansion phase (EP). In FP, pts with adv or metastatic solid tumors harboring FGF/FGFR abnormalities received futibatinib 20 mg once daily (QD) plus pembrolizumab 200 mg every 3weeks. In EP, pts with ICIs naive (Cohort A) or ICIs refractory (Cohort B) for adv or metastatic EC harboring FGFR mRNA overexpression who have received at least one prior therapy with a fluorouracil and platinum-based drug received futibatinib plus pembrolizumab at the recommended dose (RD) determined in FP. Primary endpoint was dose-limiting toxicity (DLT) in FP and overall response rate (ORR) in EP; Secondary endpoints included treatment-related adverse events (TRAEs) and disease control rate (DCR).
Results
As of November 29, 2021, 11 pts in FP, 9 pts (Cohort A) and 10 pts (Cohort B) in EP were enrolled. No DLTs were observed in FP and the RD of futibatinib in combination with pembrolizumab was determined 20 mg QD. Most common TRAEs in FP (N=11; all grade, grade ≥3) were hyperphosphatemia (91%, 27%), nausea (36%, 0%) and diarrhea (27%, 0%). As results of the interim analysis in EP, confirmed partial responses (PRs) were observed in 4 pts with squamous cell carcinoma (sq) in Cohort A; ORR was 44% with DCR of 78%. In Cohort B, confirmed PRs were observed in 2 pts [1 sq pt; 1 adenocarcinoma (adeno) pt]; ORR was 20% with DCR of 60%.
Conclusions
Futibatinib plus pembrolizumab showed well-tolerability and manageable safety profile in pts with adv or metastatic solid tumors. Preliminary antitumor activity was observed not only in ICIs naïve but also in ICIs refractory adv or metastatic EC pts regardless of sq and adeno. Enrollment in EP is ongoing including an additional cohort for ICIs naïve 1st line adv EC and ICIs refractory adv NSCLC pts.
Clinical trial identification
JapicCTI-195063.
Editorial acknowledgement
Legal entity responsible for the study
Taiho Pharmaceutical Co., Ltd.
Funding
Taiho Pharmaceutical Co., Ltd., Merck & Co., Inc.
Disclosure
K. Muro: Financial Interests, Institutional, Research Grant: Astellas, Amgen, Solasia Pharma, Sanofi, Daiichi Sankyo, Taiho, MSD, Parexel International, Merck KGaA, Pfizer, Eisai, Ono; Financial Interests, Personal and Institutional, Advisory Board: Amgen, AstraZeneca, Ono, Chugai; Financial Interests, Personal, Speaker’s Bureau: Eli Lilly, Daiichi Sankyo, Taiho, Ono, Bristol-Myers Squibb; Non-Financial Interests, Personal, Principal Investigator: Takeda. K. Kato: Financial Interests, Personal, Speaker’s Bureau: ONO Pharmaceuticals, Bristol Myers Squibb, Merck & Co.; Financial Interests, Personal, Advisory Board: ONO Pharmaceuticals, Bristol Myers Squibb, Merck & Co., BAYER, AstraZeneca, Beigene, Taiho, Merck Biopharma, Amgen, Novartis, Daiichi Sankyo; Financial Interests, Institutional, Principal Investigator: ONO Pharmaceuticals, Bristol Myers Squibb, Merck & Co., BAYER, AstraZeneca, Beigene, Chugai, Taiho, Oncolys Biopharma, Janssen Pharmaceutical. K. Chin: Financial Interests, Personal, Speaker’s Bureau: Taiho Pharma, Ono Pharmaceutical Co.Ltd., Bristol-Myers Squibb, Chugai Pharmaceutical Co., Ltd., Merck & Co., Inc. K. Nishino: Financial Interests, Personal, Speaker’s Bureau: AstraZeneca, Chugai pharmaceutical, Nippon Boehringer Ingelheim, Eli Lilly Japan, Novartis, Pfizer, Takeda Pharmaceutical Company Limited, Merck, Bristol Myers Squibb, Nippon Kayaku; Financial Interests, Personal, Advisory Board: AstraZeneca, Eli Lilly Japan, Pfizer, Janssen Pharmaceutical K.K.; Financial Interests, Institutional, Research Grant: AstraZeneca, Chugai pharmaceutical, Nippon Boehringer Ingelheim, Eli Lilly Japan, Novartis, Pfizer, Takeda Pharmaceutical Company Limited, Merck, Bristol Myers Squibb, Nippon Kayaku, ONO PHARMACEUTICAL CO., LTD., TAIHO PHARMACEUTICAL CO., LTD., MSD, AbbVie, Daiichi Sankyo Company, LIMITED, Amgen, Eisai Co., Ltd. . M. Satouchi: Financial Interests, Institutional, Principal Investigator: Taiho, Chugai, AstraZeneca, Ono, MSD, Takeda, Eisai, Amgen, Janssen, Abbvie, Daiichi-Sankyo, IQVIA, EPS; Financial Interests, Personal, Invited Speaker: Taiho, Chugai, AstraZeneca, Ono, MSD, Takeda, Eisai, Amgen, Eli Lilly, Pfizer, Novartis, Bristol Myers Squibb, Merck, Daiichi-Sankyo. H. Kawakami: Financial Interests, Personal, Speaker’s Bureau: Taiho Pharmaceutical Co. Ltd, Bristol-Myers Squibb Co. Ltd., Eli Lilly Japan K.K., MSD K.K., Ono Pharmaceutical Co. Ltd., Daiichi-Sankyo Co. Ltd., Bayer Yakuhin Ltd., Merck Biopharma Co., Ltd., Takeda Pharmaceutical Co. Ltd., Yakult Pharmaceutical Industry, Teijin Pharma Ltd., Glaxo Smith Kline K.K., Otsuka Pharmaceutical Co., Ltd., Chugai Pharmaceutical Co. Ltd.,; Financial Interests, Institutional, Sponsor/Funding: Kobayashi Pharmaceutical. Co., Ltd., Bristol-Myers Squibb Co. Ltd.; Financial Interests, Institutional, Research Grant: Eisai Co. Ltd.; Financial Interests, Personal, Advisory Board: Daiichi-Sankyo Co. Ltd.. T. Tsushima: Financial Interests, Personal, Invited Speaker: Eli LIlly Japan, Takeda, Taiho Pharma, Ono Pharmaceutical, MSD; Financial Interests, Institutional, Sponsor/Funding: Taiho Pharma, Ono Pharmaceutical, MSD, BeiGene, Chugai Pharmaceutical. 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. 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 Engagements: MSD K.K.; Financial Interests, Personal, Advisory Board: Merck Biopharma Co., Ltd. All other authors have declared no conflicts of interest.