1965MO - Phase II study of futibatinib plus pembrolizumab in patients (pts) with advanced/metastatic urothelial carcinoma (mUC): Final analysis of efficacy and safety

Background

Treatment options for pts with mUC who are platinum ineligible are limited. In this global, two-cohort, noncomparative phase 2 study (NCT04601857), the first-line combination of futibatinib (covalent FGFR1–4 inhibitor) plus pembrolizumab was assessed in platinum-ineligible pts with mUC with or without FGFR alterations.

Methods

Pts with no prior systemic therapy for mUC, measurable disease, and FGFR3 mutations or FGFR1–4 fusion/rearrangements (f/r; Cohort A), or without these alterations (Cohort B), received futibatinib 20 mg PO QD plus pembrolizumab 200 mg IV Q3W, irrespective of PD-L1 status. Primary endpoint in each cohort: confirmed objective response rate (cORR; complete/partial response [CR/PR]). Secondary endpoints: disease control rate (DCR; CR + PR + stable disease [SD]), duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety.

Results

In total, 43 pts were treated (17, Cohort A; 26, Cohort B). In Cohorts A/B, respectively, median age was 73/73 y, 82%/89% were male, 71%/46% had a baseline ECOG PS of 1, and 41%/31% had prior perioperative therapy. In Cohort A, 9 pts (53%) had FGFR3 mutations, 6 (35%) had FGFR3 f/r, 1 pt had FGFR2 f/r, and 1 pt had both an FGFR3 mutation and FGFR1 f/r. In Cohorts A/B, with a median follow-up of 16.2/24.6 months, the cORR was 47%/31%, median PFS was 8.3/4.8 months, and 12-month OS was 62%/57%. Overall, the most common treatment-related adverse events (TRAEs) were hyperphosphatemia (all grade, 23 [54%]; G3, 3 pts), diarrhea (19 [44%]; G3, 3 pts), and dry mouth (16 [37%]; all G1). The table presents key efficacy and safety data. Table: 1965MO

NE, not estimable

Conclusions

Futibatinib plus pembrolizumab had encouraging antitumor activity with durable responses in pts with mUC, particularly among pts with FGFR3 mutations or FGFR1–4 f/r. The combination was well tolerated; TRAEs were consistent with the known safety profiles of futibatinib and pembrolizumab, with no new safety concerns.

Clinical trial identification

NCT04601857.

Editorial acknowledgement

Medical writing assistance was provided by Philip Reardon, PhD, of Envision Pharma Group, funded by Taiho Oncology, Inc.

Legal entity responsible for the study

Taiho Oncology, Inc.

Funding

Taiho Oncology, Inc.

Disclosure

V.S. Koshkin: Financial Interests, Personal, Advisory Board: Janssen, Clovis, Astellas, AstraZeneca, Pfizer, EMD Serono; Financial Interests, Personal, Other, Consulting: GLG, ExpertConnect, Guidepoint; Financial Interests, Institutional, Local PI: Merck, Taiho, Eli Lilly, Clovis, Novartis; Financial Interests, Institutional, Steering Committee Member: Seagen; Financial Interests, Personal and Institutional, Research Grant: Prostate Cancer Foundation. P. Barthelemy: Financial Interests, Personal, Advisory Board: BMS, MSD, Merck, Pfizer, Ipsen, Bayer, Janssen Cilag, Astellas, Novartis, Amgen, Gilead; Financial Interests, Personal, Invited Speaker: AstraZeneca. G. Gravis: Financial Interests, Institutional, Invited Speaker: AAA, Amgen, Astellas, BMS, Janssen, MSD, Pfizer, Ipsen, AstraZeneca, alliance Merck Pfizer, Bayer, Eisai; Financial Interests, Institutional, Advisory Board: Alliance Merck-Pfizer, BMS, Janssen, Pfizer, Ipsen, Bayer, Eisai; Financial Interests, Institutional, Funding: Janssen; Financial Interests, Institutional, Coordinating PI: BMS; Non-Financial Interests, Principal Investigator: Ipsen, BMS, Merck. O. Goodman: Financial Interests, Personal, Speaker, Consultant, Advisor: Exelixis, Bayer; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca, Janssen. I. Duran: Financial Interests, Personal, Advisory Board, I have served as an advisor for this company in the last two years: Roche Genentech, MSD, Bristol Myers Squibb; Financial Interests, Personal, Invited Speaker, I have participated in different compensated educational activities sponsored by Jansen over the last two years: Jansen; Financial Interests, Personal, Invited Speaker, I have participated in different compensated educational activities sponsored by Pfizer over the last two years: Pfizer; Financial Interests, Personal, Advisory Board, I have collaborated as an advisor in different occasions over the last two years: Ipsen; Financial Interests, Personal, Invited Speaker, I have participated in different compensated educational activities sponsored by this company over the last two years: Ipsen, Bristol Myers Squibb; Financial Interests, Personal, Invited Speaker, I have participated in educational events sponsored by this company and i have received compensation for it: Merck; Financial Interests, Personal, Advisory Board, I have participated in different compensated advisory boards over the last two years: Astellas; Financial Interests, Personal, Advisory Board, I have collaborated as an advisor for this company over the last two years: Immunomedics, Inc.; Financial Interests, Personal, Invited Speaker, I have participated in educational activities sponsored by this company in the last two years: Eusa Pharma, MSD; Financial Interests, Personal, Invited Speaker, I have participated in educational activities sponsored by Novartis in the last 2 years: Novartis; Financial Interests, Personal, Invited Speaker, I have participated in compensated educational activities for this company in the last two years: Astellas; Financial Interests, Personal, Invited Speaker, I have participated in activities sponsored by this company as a guest speaker: Bayer; Financial Interests, Personal, Other, Bayer has covered expenses related to EAU 2023 including registration, travel and accommodation: Bayer; Financial Interests, Personal, Other, AstraZeneca has covered the cost of registration, accommodation and traveling related to my attendance of ASCO GU 2024: AstraZeneca; Financial Interests, Personal, Other, Merck has covered the cost related to my attendance to ASCO 2024. (Registration, travel and accommodation): Merck; Financial Interests, Personal and Institutional, Research Grant, Roche has funded research in my institution to projects under my coordination: Roche Genentech; Financial Interests, Personal, Steering Committee Member, I serve as a member of a SC for a trial sponsored by this company: Immunomedics, Inc.; Financial Interests, Personal and Institutional, Research Grant, AZ has funded research conducted in my institution related to a project where I am the PI: AstraZeneca; Financial Interests, Institutional, Coordinating PI, I am leading a study (Investigator initiated) that is funded by Gilead and sponsored by the foundation of my department (FUPOCAN). I am the national PI of this study and I dont receive any compensation for this: Gilead; Non-Financial Interests, Leadership Role, I am the president of an independent cooperative group of GU Oncologist from the north of Spain: GO NORTE; Non-Financial Interests, Member of Board of Directors, I am member of the Board of directors since 2022: ASEICA; Non-Financial Interests, Member of Board of Directors, GUARD is a GU oncology cooperative group. I am a co-founder and member of the board of directors since 2023: GUARD; Non-Financial Interests, Member of Board of Directors, Grupo Germinal is the testicular cancer Spanish group, I am currently part of the board of directors since 2020 and future president of the group: GRUPO GERMINAL; Non-Financial Interests, Principal Investigator, I am the P.I. of the PRISMA-1 study for which FUPOCAN is the sponsor. This is a multicenter national investigator initiated trial in urothelial cancer running in 10 centres in Spain: FUPOCAN; Non-Financial Interests, Leadership Role, I am the Co-Chair of the GU-TRACK for ESMO ASIA 2024: ESMO; Non-Financial Interests, Other, I am a member of the International Development and Education Award (IDEA) Steering Group for ASCO: ASCO; Non-Financial Interests, Member, I am a member and co-founder of the Spanish patient advocacy group in bladder cancer: CANVES. R. Girones Sarrio: Financial Interests, Personal, Advisory Board: BMS, Ipsen, Janssen; Financial Interests, Personal, Invited Speaker: Pfizer; Non-Financial Interests, Advisory Board: SIOG, SEOM. C. Hwang: Financial Interests, Personal, Other, Consultant: TEMPUS; Financial Interests, Personal, Advisory Board: EMD Sorono, Genzyme (Sanofi), Dendreon; Financial Interests, Personal, Stocks/Shares: Johnson and Johnson; Financial Interests, Institutional, Local PI: Merck, Seagen, AstraZeneca, Bayer, Fujifilm, Taiho, Scholar Rock, Century Therapeutics, Exelixis, Hengrui; Non-Financial Interests, Sponsor/Funding: Henry Ford Health System Government Affairs Services PAC. J. Garcia-Donas: Financial Interests, Personal, Advisory Role, Consulting: Bristol Myers Squibb, Clovis Oncology; Financial Interests, Personal, Invited Speaker, Honoraria: Roche, Bristol Myers Squibb, AstraZeneca, PharmaMar, GSK, Amgen, Clovis Oncology, Janssen-Cilag; Other, Personal, Other: Pfizer, Bristol Myers Squibb, Roche, AstraZeneca, Merck, GamaMabs Pharma, InvitroCue. R. Morales Barrera: Financial Interests, Personal, Advisory Board: AstraZeneca, Astellas, Pfizer; Financial Interests, Personal, Invited Speaker: Pfizer, Astellas, Merck; Financial Interests, Personal, Other, Congress registration/travel/accommodation: Bayer; Financial Interests, Personal, Other, Congress registration: BMS; Financial Interests, Institutional, Other, Institutional: AB Science, Aragon Pharmaceuticals, Bayer, Aveo Pharmaceuticals INC, Astellas, AstraZeneca, Blueprint Medicines Corporation, BN Immunotherapeutics INC, Boehringer Ingelheim, Clovis Oncology, Deciphera Pharmaceuticals LLC, Exelixis, Roche, Genentech, GSK, Incyte Corporation, Karyopharm Therapeutics INC, Laboratoires Leurquin Mediolanum, Lilly, Medimmune, Millennium Pharmaceuticals, Nanobiotix, Novartis, Pfizer, Sanofi-Aventis, SFJ Pharma Ltd, Teva Pharma; Financial Interests, Personal, Other, Congress registration, accommodation/travel: Merck; Non-Financial Interests, Principal Investigator: AstraZeneca, Gilead, Roche, BMS, AstraZeneca, Pfizer, Astellas, MSD, Janssen, GSK, Loxo Oncology, Tyra. M. Chisamore: Financial Interests, Personal, Full or part-time Employment: Merck & Co., Inc. M. Liu, M. Gil, G. Tomlinson, H. Elsayed: Financial Interests, Personal, Full or part-time Employment: G1 Therapeutics Inc. Y. Loriot: Financial Interests, Personal, Advisory Board: Merck Kga, Pfizer, Gilead, Seattle Genetics, Tahio; Financial Interests, Personal, Other, lectures, advisory boards: MSD, AstraZeneca, Astellas, Janssen; Financial Interests, Personal, Other, lectures, advisory boards: Roche, BMS; Financial Interests, Institutional, Research Grant: Janssen, Sanofi, MSD, Roche, Celsius; Financial Interests, Institutional, Steering Committee Member: Janssen; Financial Interests, Steering Committee Member: MSD, Astellas, Gilead/Immunomedics, Tahio; Financial Interests, Personal, Steering Committee Member: Basilea; Financial Interests, Institutional, Local PI: Pfizer, MSD, Janssen, Exelixis, AstraZeneca, Pfizer, Merck Kga, BMS, Astellas, Gilead, Incyte; Financial Interests, Institutional, Coordinating PI: Janssen; Non-Financial Interests, Member: ESMO, ASCO, AACR; Non-Financial Interests, scientific committee: ARC. All other authors have declared no conflicts of interest.