Pemigatinib + Pembrolizumab vs Pemigatinib Alone vs Standard of Care for Urothelial Carcinoma (FIGHT-205)

A Phase 2, Open-Label, Randomized, Multicenter Study to Evaluate the Efficacy and Safety of Pemigatinib Plus Pembrolizumab Versus Pemigatinib Alone Versus Standard of Care as First-Line Treatment for Metastatic or Unresectable Urothelial Carcinoma in Cisplatin-Ineligible Participants Whose Tumors Express FGFR3 Mutation or Rearrangement (FIGHT-205)

The purpose of this study is to evaluate the safety and efficacy of pemigatinib plus pembrolizumab or pemigatinib alone versus the standard of care for participants with metastatic or unresectable urothelial carcinoma who are not eligible to receive cisplatin, are harboring FGFR3 mutation or rearrangement, and who have not received prior treatment.

Study Overview

• Status: Terminated
• Conditions: Metastatic Urothelial Carcinoma; Unresectable Urothelial Carcinoma
• Intervention / Treatment: Drug: Pemigatinib; Drug: Pembrolizumab; Drug: Gemcitabine; Drug: Carboplatin

• Study Type: Interventional
• Enrollment (Actual): 7
• Phase: Phase 2

Contacts and Locations

Study Locations

• Austria
  • Vienna, Austria, 01160
    • Wilhelminenspital
• Belgium
  • Charleroi, Belgium, 06000
    • Grand Hôpital de Charleroi
  • Leuven, Belgium, 03000
    • Universitaire Ziekenhuis Leuven - Gasthuisberg
• Canada
  • New Brunswick
    • Moncton, New Brunswick, Canada, E1C 6Z8
      • Moncton Hospital - Horizon Health Network
• Finland
  • Helsinki, Finland, 00029
    • Helsinki University Meilahti Tower Hospital
  • Tampere, Finland, 33520
    • Fonk Onkologian Klinikka
  • Turku, Finland, 20521
    • Turku University Hospital, Sct Unit
• France
  • Besançon, France, 25000
    • CENTRE HOSPITALIER UNIVERSITAIRE de BESANCON
  • Bordeaux, France, 33075
    • Groupe Hospitalier Pellegrin Tripode
  • La Chaussée-Saint-Victor, France, 41260
    • Polyclinique de Blois
  • Nîmes, France, 30029
    • CHU Nimes
  • Paris, France, 75013
    • Groupe Hospitalier Pitie-Salpetriere
  • Paris, France, 75014
    • Hopital Cochin Cancerologie
  • Paris, France, 75015
    • Hopital Europeen Georges Pompidou (HEGP)
  • Poitiers, France, 86021
    • Centre Hospitalier Universitaire de Poitiers
  • Strasbourg, France, 67091
    • Chu de Strasbourg Hopitaux Universitaires Service D Hematologie
  • Toulouse, France, 31100
    • Institut Claudius Regaud Oncopole Toulouse
• Germany
  • Mönchengladbach, Germany, 41063
    • Kliniken Maria Hilf
• Ireland
  • Waterford, Ireland, X91 ER8E
    • University Hospital Waterford
• Italy
  • Bari, Italy, 70124
    • Iov - Istituto Oncologico Veneto Irccs
  • Bari, Italy, 70124
    • Istituto Tumori Giovanni Paolo Ii Irccs Ospedale Oncologico Bari
  • Bologna, Italy, 40138
    • L AZIENDA OSPEDALIERO-UNIVERSITARIA DI BOLOGNA POLICLINICO S. ORSOLA � MALPIGHI
  • Meldola, Italy, 47014
    • Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori
  • Milan, Italy, 20133
    • Fondazione IRCCS Istituto Nazionale dei Tumori
  • Milan, Italy, 20122
    • Fondazione Irccs Ca Granda Ospedale Maggiore
  • Milan, Italy, 20141
    • Ieo Istituto Europeo Di Oncologia Irccs
  • Napoli, Italy, 80131
    • Istituto Nazionale Tumori Fondazione Irccs G. Pascale
  • Roma, Italy, 00128
    • UNIVERSIT� CAMPUS BIO-MEDICO DI ROMA
  • Rozzano, Italy, 20089
    • IRRCS Instituto Clinico Humanitas
  • Terni, Italy, 05100
    • Azosp S.Maria Sc Oncologia
• Japan
  • Chiba, Japan, 260-8717
    • Chiba Cancer Center
  • Chiba, Japan, 260-8677
    • Chiba University Hospital
  • Fukuoka, Japan, 811-1395
    • National Hospital Organization Kyushu Cancer Center
  • Hidaka-shi, Japan, 350-1298
    • Saitama Medical University International Medical Center
  • Hirosaki-shi, Japan, 036-8563
    • Hirosaki University Hospital
  • Hokkaido, Japan, 060-8543
    • Sapporo Medical University Hospital
  • Hokkaido, Japan, 040-8611
    • Hakodate Goryokaku Hospital
  • Itabashi-ku, Japan, 173-8610
    • Nihon University Itabashi Hospital
  • Kashihara-shi, Japan, 634-8522
    • Nara Medical University Hospital
  • Kawasaki-shi, Japan, 216-8511
    • St. Marianna University School of Medicine Hospital
  • Kita-gun, Japan, 761-0793
    • Kagawa University Hospital
  • Matsuyama, Japan, 791-0280
    • NHO Shikoku Cancer Center
  • Minatoku, Japan, 105-8470
    • Toranomon Hospital
  • Osaka, Japan, 541-8567
    • Osaka International Cancer Institute
  • Saitama-shi, Japan, 330-8503
    • Saitama Medical Center Jichi Medical University
  • Sendai, Japan, 980-8574
    • Tohoku University Hospital
  • Shimotsuke-shi, Japan, 329-0498
    • Jichi Medical University Hospital
  • Shinjuku-ku, Japan, 160-8582
    • Keio University Hospital
  • Suita-shi, Japan, 565-0871
    • Osaka University Hospital
  • Tokyo, Japan, 104-0045
    • National Cancer Center Hospital
  • Toyama, Japan, 930-0194
    • Toyama University Hospital
• Poland
  • Olsztyn, Poland, 10-513
    • Olsztyński Ośrodek Onkologiczny Kopernik
• Portugal
  • Lisbon, Portugal, 1400-048
    • Champalimaud Foundation - Champalimaud Centre For the Unknown (Champalimaud Cancer Center)
• Romania
  • Constanța, Romania, 900591
    • Spitalul Clinic Judetean de Urgenta 'Sf Apostol Andrei' Constanta
• Slovakia
  • Žilina, Slovakia, 01207
    • Fakultna nemocnica s poliklinikou Zilina
• Spain
  • Barcelona, Spain, 08036
    • Hospital Clínic i Provincial
  • Barcelona, Spain, 08908
    • Ico Institut Catala D Oncologia
  • Girona, Spain, 17007
    • ICO Girona
  • Madrid, Spain, 28040
    • Hospital Clinico San Carlos
  • Madrid, Spain, 28041
    • Hospital Universitario 12 de Octubre
  • Madrid, Spain, 28046
    • Hospital Universitario de La Paz
  • Madrid, Spain, 28050
    • Hospital Universitario HM Sanchinarro
  • Majadahonda, Spain, 28222
    • Hospital Puerta de Hierro
  • Seville, Spain, 41013
    • Hospital Universitario Virgen del Rocio
  • Valencia, Spain, 46010
    • Hospital Clínico Universitario de Valencia
• United Kingdom
  • London, United Kingdom, EC1A 7BE
    • Barts Health Nhs Trust - St Bartholomews Hospital
• United States
  • California
    • Greenbrae, California, United States, 94904
      • Marin Cancer Care
  • Delaware
    • Newark, Delaware, United States, 19713
      • Christiana Care Helen F. Graham Cancer Center
  • Georgia
    • Marietta, Georgia, United States, 30067
      • Cotton-O'Neil Clinical Research Center, Hematology & Oncology
  • Illinois
    • Springfield, Illinois, United States, 62702
      • Simmons Cancer Institute at SIU
  • Kansas
    • Westwood, Kansas, United States, 66205
      • The University of Kansas Cancer Center
  • Maine
    • Biddeford, Maine, United States, 04005
      • Smhc Cancer Blood Disorders
  • New Jersey
    • Florham Park, New Jersey, United States, 07932
      • Summit Medical Group
  • New York
    • New York, New York, United States, 10029
      • Mount Sinai School of Medicine
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health & Science University
  • South Carolina
    • Charleston, South Carolina, United States, 29414
      • Charleston Hematology Oncology Associates
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt-Ingram Cancer Center
  • Texas
    • Fort Worth, Texas, United States, 76104
      • The Center for Cancer and Blood Disorders
    • Houston, Texas, United States, 77030
      • Onc Consultants Pharmacy 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Histologically documented metastatic or unresectable urothelial carcinoma. Both transitional cell and mixed transitional cell histologies are allowed, provided urothelial component is ≥ 50%.
• At least 1 measurable target lesion per RECIST v1.1.
• Must be ineligible to receive cisplatin. Patients ineligible for any platinum-based chemotherapy are allowed.
• Known FGFR3 mutation or rearrangement confirmed by the central laboratory prior to randomization.
• Central laboratory test result of PD-L1 status is mandatory at screening.
• Have received no prior systemic chemotherapy for metastatic or unresectable urothelial carcinoma (except adjuvant platinum-based chemotherapy following radical cystectomy, with recurrence > 12 months from completion of therapy, or neo-adjuvant platinum-based chemotherapy, with recurrence > 12 months since completion of therapy).
• Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2.
• Willingness to avoid pregnancy or fathering children.

Exclusion Criteria:

• Prior receipt of a selective FGFR inhibitor for any indication or reason.
• Prior receipt of an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent, or with an agent directed to another co-inhibitory T-cell receptor.
• Receipt of anticancer medications or investigational drugs for unresectable and/or metastatic disease.
• Concurrent anticancer therapy, except for treatment allowed per protocol.
• Has disease that is suitable for local therapy administered with curative intent.
• Has tumor with any neuroendocrine or small cell component.
• Current evidence of clinically significant corneal or retinal disorder as confirmed by ophthalmologic examination.
• Has received prior radiotherapy to a metastatic site without the use of chemotherapy radiosensitization within 3 weeks of the first dose of study treatment, with the exception of palliative radiotherapy to bone lesions, which is allowed if completed 2 weeks before the start of study treatment.
• Has central nervous system metastases, unless the participant has completed local therapy (eg, whole brain radiation therapy, surgery, radiosurgery) and has discontinued use of corticosteroids for this indication for at least 4 weeks before starting treatment in this study.
• Known additional malignancy that is progressing or required active treatment within the past 3 years
• Laboratory values outside the protocol-defined range at screening.
• Clinically significant or uncontrolled cardiac disease.
• History of autoimmune disease that has required systemic treatment in past 2 years.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Pemigatinib + Pembrolizumab; Combination of pemigatinib (13.5 milligrams [mg] once a day orally) plus pembrolizumab (200 mg every 3 weeks [Q3W] intravenously [IV])	Drug: Pemigatinib; 13.5 mg once a day orally; Other Names: INCB054828; Drug: Pembrolizumab; 200 mg Q3W intravenously; Other Names: Keytruda®
Experimental: Pemigatinib; Pemigatinib (13.5 mg once a day orally) alone	Drug: Pemigatinib; 13.5 mg once a day orally; Other Names: INCB054828
Active Comparator: Standard of Care; Either gemcitabine plus carboplatin or pembrolizumab as standard of care. Gemcitabine 1000 mg/meters squared (m^2) IV over 30 minutes on Days 1 and 8, followed by carboplatin (dosed to target area under the concentration-time curve [AUC] of 5 mg/milliliters [mL]/minute [min] or 4.5 mg/mL/min if required per local guidelines) on Day 1 or 2 of each 3-week cycle. Pembrolizumab 200 mg IV on Day 1 of each 21-day treatment cycle for up to 35 cycles or disease progression.	Drug: Gemcitabine; 1000 mg/m^2 IV over 30 minutes on Days 1 and 8 of each 3-week cycle; Drug: Carboplatin; Dosed to target AUC of 5 mg/mL/min or 4.5 mg/mL/min if required per local guidelines on Day 1 or 2 of each 3-week cycle

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free Survival (PFS)	PFS was defined as the time from the randomization date until the date of disease progression (as measured by a blinded independent central review [BICR] per Response Evaluation Criteria in Solid Tumors version 1.1 [RECIST v1.1]) or death due to any cause, whichever occurred first.	up to 130 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS)	OS was defined as the time from the date of randomization until death due to any cause.	up to 225 days
Objective Response Rate (ORR)	ORR was defined as the proportion of participants with a best overall response of complete response (CR) or partial response (PR) per RECIST v1.1 (as measured by BICR).	up to 148 days
Duration of Response (DOR)	DOR was defined as the time from the date of the first assessment of CR or PR until the date of the first disease progression (per RECIST v1.1) or death, whichever occurred first (as measured by BICR).	up to 148 days
Number of Participants With Treatment-emergent Adverse Events	A treatment-emergent adverse event was defined as an adverse event that was either reported for the first time or the worsening of a pre-existing event after the first dose of study drug until 30 days after the last dose of study drug.	up to 178 days
EORTC QLQ-C30 Score	The European Organization for the Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ-C30) contains 30 items and measures 5 functional dimensions (i.e., physical, role, emotional, cognitive, and social), 3 symptom items (i.e., fatigue, nausea/vomiting, and pain), 6 single items (i.e., dyspnea, sleep disturbance, appetite loss, constipation, diarrhea, and financial impact), and a global health and quality of life scale. For each scale and single item, a linear transformation was applied to standardize the scores between 0 (worst) and 100 (best) as described in the EORTC QLQ-C30 Scoring Manual.	up to 160 days
Change From Baseline in the EORTC QLQ-C30 Score	The European Organization for the Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ-C30) contains 30 items and measures 5 functional dimensions (i.e., physical, role, emotional, cognitive, and social), 3 symptom items (i.e., fatigue, nausea/vomiting, and pain), 6 single items (i.e., dyspnea, sleep disturbance, appetite loss, constipation, diarrhea, and financial impact), and a global health and quality of life scale. For each scale and single item, a linear transformation was applied to standardize the scores between 0 (worst) and 100 (best) as described in the EORTC QLQ-C30 Scoring Manual. Change from Baseline was calculated as the post-Baseline value minus the Baseline value.	Baseline; up to 160 days
Number of Participants With the Indicated EQ-5D-5L Dimension Scores	The EQ-5D-5L is a standardized instrument for use as a measure of health outcome. The EQ-5D-5L descriptive system is composed of 5 dimensions (mobility, self-case, usual activities, pain/discomfort, and anxiety/depression). Each dimension has 5 response levels, which are coded by single-digit numbers: 1 = no problems, 2 = slight problems, 3 = moderate problems, 4 = severe problems, 5 = unable to/extreme problems. The EQ-5D-5L also includes a graded (0 [worst overall health] to 100 [best overall health]) vertical visual analog scale that provides a quantitative measure of the participant's perception of their overall health.	up to 160 days
Change From Baseline in the EQ-5D-5L EQ Visual Analog Scale Score	The EQ-5D-5L is a standardized instrument for use as a measure of health outcome. The EQ-5D-5L descriptive system is composed of 5 dimensions (mobility, self-case, usual activities, pain/discomfort, and anxiety/depression). Each dimension has 5 response levels, which are coded by single-digit numbers: 1 = no problems, 2 = slight problems, 3 = moderate problems, 4 = severe problems, 5 = unable to/extreme problems. The EQ-5D-5L also includes a graded (0 [worst overall health] to 100 [best overall health]) vertical visual analog scale that provides a quantitative measure of the participant's perception of their overall health.	Baseline; up to 160 days

Collaborators and Investigators

• Sponsor: Incyte Corporation
• Investigators: Study Director: Luis Feliz Vinas, MD, Incyte Corporation

Study record dates

Study Major Dates

• Study Start (Actual): May 14, 2020
• Primary Completion (Actual): April 18, 2021
• Study Completion (Actual): April 18, 2021

Study Registration Dates

• First Submitted: June 28, 2019
• First Submitted That Met QC Criteria: June 28, 2019
• First Posted (Actual): July 1, 2019

Study Record Updates

• Last Update Posted (Estimated): November 4, 2025
• Last Update Submitted That Met QC Criteria: October 20, 2025
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Keywords: metastatic; Urothelial carcinoma; unresectable; cisplatin-ineligible; fibroblast growth factor receptor (FGFR) inhibitor; FGFR3 mutation; FGFR3 rearrangement
• Additional Relevant MeSH Terms: Bone Diseases; Musculoskeletal Diseases; Pathologic Processes; Neoplasms; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Neoplastic Processes; Carcinoma; Craniofacial Abnormalities; Musculoskeletal Abnormalities; Congenital Abnormalities; Bone Diseases, Developmental; Limb Deformities, Congenital; Synostosis; Dysostoses; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Pathological Conditions, Signs and Symptoms; Craniosynostoses; Syndactyly; Neoplasm Metastasis; Carcinoma, Transitional Cell; Acrocephalosyndactylia; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Coordination Complexes; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Gemcitabine; Carboplatin; pembrolizumab; pemigatinib
• Other Study ID Numbers: INCB 54828-205; 2019-000721-50 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Incyte shares data with qualified external researchers after a research proposal is submitted. These requests are reviewed and approved by a review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

The trial data availability is according to the criteria and process described on https://www.incyte.com/our-company/compliance-and-transparency

• IPD Sharing Time Frame: Data will be shared after the primary publication or 2 years after the study has ended for market authorized products and indications.
• IPD Sharing Access Criteria: Data from eligible studies will be shared with qualified researchers according to the criteria and process described in the Data Sharing section of the www.incyteclinicaltrials.com website. For approved requests, the researchers will be granted access to anonymized data under the terms of a data sharing agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No