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

Metastatic Urothelial Carcinoma Clinical Trial

Official title:

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)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04003610
• Other study ID #: INCB 54828-205
• Status: Terminated
• Phase: Phase 2
• Start date: May 14, 2020
• Est. completion date: April 18, 2021

Study information

• Verified date: May 2022
• Source: Incyte Corporation
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 7
• Est. completion date: April 18, 2021
• Est. primary completion date: April 18, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Transitional Cell
• Metastatic Urothelial Carcinoma
• Unresectable Urothelial Carcinoma

Intervention

Drug:
• Pemigatinib
13.5 mg once a day orally
• Pembrolizumab
200 mg Q3W intravenously
• Gemcitabine
1000 mg/m^2 IV over 30 minutes on Days 1 and 8 of each 3-week cycle
• 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

Locations

Country	Name	City	State
Austria	Wilhelminenspital	Vienna
Belgium	Grand Hopital de Charleroi	Charleroi
Belgium	Universitaire Ziekenhuis Leuven - Gasthuisberg	Leuven
Canada	Moncton Hospital - Horizon Health Network	Moncton	New Brunswick
Finland	Helsinki University Meilahti Tower Hospital	Helsinki
Finland	Fonk Onkologian Klinikka	Tampere
Finland	Turku University Hospital, Sct Unit	Turku
France	Centre Hospitalier Universitaire de Besancon	Besancon
France	Groupe Hospitalier Pellegrin Tripode	Bordeaux
France	Polyclinique de Blois	La Chaussee-saint-victor
France	Chu Nimes	Nimes
France	Groupe Hospitalier Pitie-Salpetriere	Paris
France	Hopital Cochin Cancerologie	Paris
France	Hopital Europeen Georges Pompidou (Hegp)	Paris
France	Centre Hospitalier Universitaire de Poitiers	Poitiers
France	Chu de Strasbourg Hopitaux Universitaires Service D Hematologie	Strasbourg
France	Institut Claudius Regaud Oncopole Toulouse	Toulouse
Germany	Kliniken Maria Hilf	Moenchengladbach
Ireland	University Hospital Waterford	Waterford
Italy	Iov - Istituto Oncologico Veneto Irccs	Bari
Italy	Istituto Tumori Giovanni Paolo Ii Irccs Ospedale Oncologico Bari	Bari
Italy	L AZIENDA OSPEDALIERO-UNIVERSITARIA DI BOLOGNA POLICLINICO S. ORSOLA � MALPIGHI	Bologna
Italy	Istituto Scientifico Romagnolo Per Lo Studio E La Cura Dei Tumori	Meldola
Italy	Fondazione Irccs Ca Granda Ospedale Maggiore	Milan
Italy	Fondazione Irccs Istituto Nazionale Dei Tumori	Milano
Italy	Ieo Istituto Europeo Di Oncologia Irccs	Milano
Italy	Istituto Nazionale Tumori Fondazione Irccs G. Pascale	Napoli
Italy	UNIVERSIT� CAMPUS BIO-MEDICO DI ROMA	Roma
Italy	Irrcs Instituto Clinico Humanitas	Rozzano
Italy	Azosp S.Maria Sc Oncologia	Terni
Japan	Chiba Cancer Center	Chiba
Japan	Chiba University Hospital	Chiba
Japan	National Hospital Organization Kyushu Cancer Center	Fukuoka
Japan	Saitama Medical University International Medical Center	Hidaka-shi
Japan	Hirosaki University Hospital	Hirosaki-shi
Japan	Hakodate Goryokaku Hospital	Hokkaido
Japan	Sapporo Medical University Hospital	Hokkaido
Japan	Nihon University Itabashi Hospital	Itabashi-ku
Japan	Nara Medical University Hospital	Kashihara-shi
Japan	St. Marianna University School of Medicine Hospital	Kawasaki-shi
Japan	Kagawa University Hospital	Kita-gun
Japan	Nho Shikoku Cancer Center	Matsuyama
Japan	Toranomon Hospital	Minato-ku
Japan	Osaka International Cancer Institute	Osaka-shi
Japan	Saitama Medical Center Jichi Medical University	Saitama-shi
Japan	Tohoku University Hospital	Sendai-shi
Japan	Jichi Medical University Hospital	Shimotsuke-shi
Japan	Keio University Hospital	Shinjuku-ku
Japan	Osaka University Hospital	Suita-shi
Japan	National Cancer Center Hospital	Tokyo
Japan	Toyama University Hospital	Toyama
Poland	Olsztynski Osrodek Onkologiczny Kopernik	Olsztyn
Portugal	Champalimaud Foundation - Champalimaud Centre For the Unknown (Champalimaud Cancer Center)	Lisboa
Romania	Spitalul Clinic Judetean de Urgenta 'Sf Apostol Andrei' Constanta	Constanta
Slovakia	Fakultna Nemocnica S Poliklinikou Zilina	Zilina
Spain	Hospital Clinic I Provincial	Barcelona
Spain	Ico Institut Catala D Oncologia	Barcelona
Spain	Ico Girona	Girona
Spain	Hospital Clinico San Carlos	Madrid
Spain	Hospital Universitario 12 de Octubre	Madrid
Spain	Hospital Universitario de La Paz	Madrid
Spain	Hospital Universitario Hm Sanchinarro	Madrid
Spain	Hospital Puerta de Hierro	Majadahonda
Spain	Hospital Universitario Virgen Del Rocio	Sevilla
Spain	Hospital Clinico Universitario de Valencia	Valencia
United Kingdom	Barts Health Nhs Trust - St Bartholomews Hospital	London
United States	Smhc Cancer Blood Disorders	Biddeford	Maine
United States	Charleston Hematology Oncology Associates	Charleston	South Carolina
United States	Summit Medical Group	Florham Park	New Jersey
United States	The Center For Cancer and Blood Disorders	Fort Worth	Texas
United States	Marin Cancer Care	Greenbrae	California
United States	Onc Consultants Pharmacy 2	Houston	Texas
United States	Cotton-O'Neil Clinical Research Center, Hematology & Oncology	Marietta	Georgia
United States	Vanderbilt-Ingram Cancer Center	Nashville	Tennessee
United States	Mount Sinai School of Medicine	New York	New York
United States	Christiana Care Helen F. Graham Cancer Center	Newark	Delaware
United States	Oregon Health & Science University	Portland	Oregon
United States	Simmons Cancer Institute At Siu	Springfield	Illinois
United States	The University of Kansas Cancer Center	Westwood	Kansas

Sponsors (1)

Lead Sponsor	Collaborator
Incyte Corporation

Countries where clinical trial is conducted

United States,  Austria,  Belgium,  Canada,  Finland,  France,  Germany,  Ireland,  Italy,  Japan,  Poland,  Portugal,  Romania,  Slovakia,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Overall Survival (OS)	OS was defined as the time from the date of randomization until death due to any cause.	up to 225 days
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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