Pemigatinib + Pembrolizumab vs Pemigatinib Alone vs Standard of Care for Urothelial Carcinoma (FIGHT-205)
- Conditions
- Unresectable Urothelial CarcinomaMetastatic Urothelial Carcinoma
- Interventions
- Registration Number
- NCT04003610
- Lead Sponsor
- Incyte Corporation
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 7
- 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.
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Pemigatinib + Pembrolizumab Pemigatinib Combination of pemigatinib (13.5 milligrams \[mg\] once a day orally) plus pembrolizumab (200 mg every 3 weeks \[Q3W\] intravenously \[IV\]) Pemigatinib Pemigatinib Pemigatinib (13.5 mg once a day orally) alone Pemigatinib + Pembrolizumab Pembrolizumab Combination of pemigatinib (13.5 milligrams \[mg\] once a day orally) plus pembrolizumab (200 mg every 3 weeks \[Q3W\] intravenously \[IV\]) Standard of Care Gemcitabine 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. Standard of Care Carboplatin 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.
- Primary Outcome Measures
Name Time Method Progression-free Survival (PFS) up to 130 days 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.
- Secondary Outcome Measures
Name Time Method Number of Participants With Treatment-emergent Adverse Events up to 178 days 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.
Change From Baseline in the EQ-5D-5L EQ Visual Analog Scale Score Baseline; up to 160 days 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.
Overall Survival (OS) up to 225 days OS was defined as the time from the date of randomization until death due to any cause.
Objective Response Rate (ORR) up to 148 days 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).
EORTC QLQ-C30 Score up to 160 days 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.
Duration of Response (DOR) up to 148 days 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).
Change From Baseline in the EORTC QLQ-C30 Score Baseline; up to 160 days 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.
Number of Participants With the Indicated EQ-5D-5L Dimension Scores up to 160 days 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.
Trial Locations
- Locations (79)
Oregon Health & Science University
🇺🇸Portland, Oregon, United States
The University of Kansas Cancer Center
🇺🇸Westwood, Kansas, United States
Mount Sinai School of Medicine
🇺🇸New York, New York, United States
Helsinki University Meilahti Tower Hospital
🇫🇮Helsinki, Finland
Centre Hospitalier Universitaire de Besancon
🇫🇷Besancon, France
Moncton Hospital - Horizon Health Network
🇨🇦Moncton, New Brunswick, Canada
Charleston Hematology Oncology Associates
🇺🇸Charleston, South Carolina, United States
Grand Hopital de Charleroi
🇧🇪Charleroi, Belgium
Chu Nimes
🇫🇷Nimes, France
Groupe Hospitalier Pellegrin Tripode
🇫🇷Bordeaux, France
Groupe Hospitalier Pitie-Salpetriere
🇫🇷Paris, France
Wilhelminenspital
🇦🇹Vienna, Austria
Turku University Hospital, Sct Unit
🇫🇮Turku, Finland
University Hospital Waterford
🇮🇪Waterford, Ireland
Irrcs Instituto Clinico Humanitas
🇮🇹Rozzano, Italy
The Center For Cancer and Blood Disorders
🇺🇸Fort Worth, Texas, United States
Fonk Onkologian Klinikka
🇫🇮Tampere, Finland
L AZIENDA OSPEDALIERO-UNIVERSITARIA DI BOLOGNA POLICLINICO S. ORSOLA � MALPIGHI
🇮🇹Bologna, Italy
Polyclinique de Blois
🇫🇷La Chaussee-saint-victor, France
Onc Consultants Pharmacy 2
🇺🇸Houston, Texas, United States
Iov - Istituto Oncologico Veneto Irccs
🇮🇹Bari, Italy
Azosp S.Maria Sc Oncologia
🇮🇹Terni, Italy
Hopital Cochin Cancerologie
🇫🇷Paris, France
UNIVERSIT� CAMPUS BIO-MEDICO DI ROMA
🇮🇹Roma, Italy
Centre Hospitalier Universitaire de Poitiers
🇫🇷Poitiers, France
Chu de Strasbourg Hopitaux Universitaires Service D Hematologie
🇫🇷Strasbourg, France
Hopital Europeen Georges Pompidou (Hegp)
🇫🇷Paris, France
Istituto Tumori Giovanni Paolo Ii Irccs Ospedale Oncologico Bari
🇮🇹Bari, Italy
Istituto Scientifico Romagnolo Per Lo Studio E La Cura Dei Tumori
🇮🇹Meldola, Italy
Fondazione Irccs Istituto Nazionale Dei Tumori
🇮🇹Milano, Italy
Ieo Istituto Europeo Di Oncologia Irccs
🇮🇹Milano, Italy
Fondazione Irccs Ca Granda Ospedale Maggiore
🇮🇹Milan, Italy
Institut Claudius Regaud Oncopole Toulouse
🇫🇷Toulouse, France
Kliniken Maria Hilf
🇩🇪Moenchengladbach, Germany
Saitama Medical University International Medical Center
🇯🇵Hidaka-shi, Japan
Hakodate Goryokaku Hospital
🇯🇵Hokkaido, Japan
Ico Institut Catala D Oncologia
🇪🇸Barcelona, Spain
Toyama University Hospital
🇯🇵Toyama, Japan
Hospital Clinico San Carlos
🇪🇸Madrid, Spain
Hospital Clinico Universitario de Valencia
🇪🇸Valencia, Spain
Barts Health Nhs Trust - St Bartholomews Hospital
🇬🇧London, United Kingdom
Hospital Puerta de Hierro
🇪🇸Majadahonda, Spain
Spitalul Clinic Judetean de Urgenta 'Sf Apostol Andrei' Constanta
🇷🇴Constanta, Romania
Cotton-O'Neil Clinical Research Center, Hematology & Oncology
🇺🇸Marietta, Georgia, United States
Simmons Cancer Institute At Siu
🇺🇸Springfield, Illinois, United States
Marin Cancer Care
🇺🇸Greenbrae, California, United States
Christiana Care Helen F. Graham Cancer Center
🇺🇸Newark, Delaware, United States
Universitaire Ziekenhuis Leuven - Gasthuisberg
🇧🇪Leuven, Belgium
Istituto Nazionale Tumori Fondazione Irccs G. Pascale
🇮🇹Napoli, Italy
Chiba University Hospital
🇯🇵Chiba, Japan
Hirosaki University Hospital
🇯🇵Hirosaki-shi, Japan
St. Marianna University School of Medicine Hospital
🇯🇵Kawasaki-shi, Japan
Nihon University Itabashi Hospital
🇯🇵Itabashi-ku, Japan
Nara Medical University Hospital
🇯🇵Kashihara-shi, Japan
Kagawa University Hospital
🇯🇵Kita-gun, Japan
Osaka International Cancer Institute
🇯🇵Osaka-shi, Japan
Tohoku University Hospital
🇯🇵Sendai-shi, Japan
Toranomon Hospital
🇯🇵Minato-ku, Japan
Jichi Medical University Hospital
🇯🇵Shimotsuke-shi, Japan
Keio University Hospital
🇯🇵Shinjuku-ku, Japan
Osaka University Hospital
🇯🇵Suita-shi, Japan
Hospital Universitario de La Paz
🇪🇸Madrid, Spain
Olsztynski Osrodek Onkologiczny Kopernik
🇵🇱Olsztyn, Poland
Champalimaud Foundation - Champalimaud Centre For the Unknown (Champalimaud Cancer Center)
🇵🇹Lisboa, Portugal
Hospital Clinic I Provincial
🇪🇸Barcelona, Spain
Ico Girona
🇪🇸Girona, Spain
Fakultna Nemocnica S Poliklinikou Zilina
🇸🇰Zilina, Slovakia
Hospital Universitario 12 de Octubre
🇪🇸Madrid, Spain
Hospital Universitario Hm Sanchinarro
🇪🇸Madrid, Spain
Hospital Universitario Virgen Del Rocio
🇪🇸Sevilla, Spain
Chiba Cancer Center
🇯🇵Chiba, Japan
National Hospital Organization Kyushu Cancer Center
🇯🇵Fukuoka, Japan
Vanderbilt-Ingram Cancer Center
🇺🇸Nashville, Tennessee, United States
Smhc Cancer Blood Disorders
🇺🇸Biddeford, Maine, United States
Sapporo Medical University Hospital
🇯🇵Hokkaido, Japan
Nho Shikoku Cancer Center
🇯🇵Matsuyama, Japan
Saitama Medical Center Jichi Medical University
🇯🇵Saitama-shi, Japan
National Cancer Center Hospital
🇯🇵Tokyo, Japan
Summit Medical Group
🇺🇸Florham Park, New Jersey, United States