A Study to Evaluate the Efficacy and Safety of Pemigatinib (INCB054828) in Subjects With Urothelial Carcinoma - (FIGHT-201)

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the overall response rate (ORR) of pemigatinib as a monotherapy in the treatment of metastatic or surgically unresectable urothelial carcinoma harboring FGF/FGFR alterations.

Official Title
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A Phase 2, Open-Label, Single-Agent, Multicenter Study to Evaluate the Efficacy and Safety of Pemigatinib (INCB054828) in Subjects With Metastatic or Surgically Unresectable Urothelial Carcinoma Harboring FGF/FGFR Alterations - (FIGHT-201)

Conditions
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UC (Urothelial Cancer)

Intervention / Treatment
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* Drug: pemigatinib
* Drug: pemigatinib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 20 years and older in Japan Histologically documented metastatic or surgically unresectable urothelial carcinoma; may include primary site from urethra, ureters, upper tract, renal pelvis, and bladder. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2. Life expectancy ≥ 12 weeks. Radiographically measurable per RECIST v1.1. Documented FGF/FGFR alteration and have either 1a) failed at least 1 previous treatment for their metastatic or surgically unresectable urothelial carcinoma (ie, chemotherapy, immunotherapy) or 1b) have not received chemotherapy due to poor ECOG status or 2) have insufficient renal function. Exclusion Criteria: Prior receipt of a selective FGFR inhibitor. Use of any potent CYP3A4 inhibitors or inducers within 14 days or 5 half-lives (whichever is shorter) before the first dose of study drug. Inability or unwillingness to swallow pemigatinib or significant gastrointestinal disorder(s) that could interfere with the absorption, metabolism, or excretion of pemigatinib.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort A-ID (Intermittent Dose) Pemigatinib<br>Pemigatinib in subjects with FGFR3 mutations or fusions. | Drug: pemigatinib<br>* Pemigatinib once a day by mouth for 2 consecutive weeks and 1 week off therapy.<br>* Other names: INCB054828;|
| Experimental: Cohort A-CD (Continuous Dose) Pemigatinib<br>Pemigatinib in subjects with FGFR3 mutations or fusions. | Drug: pemigatinib<br>* Pemigatinib once a day by mouth continuously.<br>* Other names: INCB054828;|
| Experimental: Cohort B Pemigatinib<br>Pemigatinib in subjects with other FGF/FGFR alterations. | Drug: pemigatinib<br>* Pemigatinib once a day by mouth for 2 consecutive weeks and 1 week off therapy.<br>* Other names: INCB054828;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (ORR) in Participants With FGFR3 Mutations or Fusions on a CD Regimen | ORR was defined as the percentage of participants with a best overall response of complete response (CR) or partial response (PR) at any post-Baseline visit prior to first progressive disease (PD), per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 (v1.1). CR: disappearance of all target and non-target lesions and no appearance of any new lesions. Any pathological lymph nodes (whether target or non-target) must have a reduction in the short axis to <10 millimeters (mm). PR: complete disappearance or at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference the baseline sum diameters, no new lesions, and no progression of non-target lesions. Response was based on review of scans by an independent centralized radiological review committee. Response was confirmed. | up to 1138 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ORR in Participants With FGFR3 Mutations or Fusions on an ID Regimen | ORR was defined as the percentage of participants with a best overall response of CR or PR at any post-Baseline visit prior to first PD, per RECIST v1.1. CR: disappearance of all target and non-target lesions and no appearance of any new lesions. Any pathological lymph nodes (whether target or non-target) must have a reduction in the short axis to <10 millimeters (mm). PR: complete disappearance or at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference the baseline sum diameters, no new lesions, and no progression of non-target lesions. Response was based on review of scans by an independent centralized radiological review committee. Response was confirmed. | up to 817 days | 
| ORR in Participants With All Other FGF/FGFR Alterations | ORR was defined as the percentage of participants with a best overall response of CR or PR at any post-Baseline visit prior to first PD, per RECIST v1.1. CR: disappearance of all target and non-target lesions and no appearance of any new lesions. Any pathological lymph nodes (whether target or non-target) must have a reduction in the short axis to <10 millimeters (mm). PR: complete disappearance or at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference the baseline sum diameters, no new lesions, and no progression of non-target lesions. Response was based on review of scans by an independent centralized radiological review committee. Response was confirmed. | up to 1198 days | 
| ORR in All Participants on an ID or CD Regimen in Combined Cohorts | ORR was defined as the percentage of participants with a best overall response of CR or PR at any post-Baseline visit prior to first PD, per RECIST v1.1. CR: disappearance of all target and non-target lesions and no appearance of any new lesions. Any pathological lymph nodes (whether target or non-target) must have a reduction in the short axis to <10 millimeters (mm). PR: complete disappearance or at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference the baseline sum diameters, no new lesions, and no progression of non-target lesions. Response was based on review of scans by an independent centralized radiological review committee. Response was confirmed. | up to 1198 days | 
| Number of Participants With Any Treatment-emergent Adverse Event (TEAE) | An adverse event (AE) was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related, that occurred after a participant provided informed consent. Abnormal laboratory values or test results occurring after informed consent constituted AEs only if they induced clinical signs or symptoms, were considered clinically meaningful, required therapy (e.g., hematologic abnormality that required transfusion), or required changes in the study drug(s). A TEAE was any AE either reported for the first time or the worsening of a pre-existing event after the first dose of study drug and within 30 days of the last dose of study drug. | up to approximately 25 weeks | 
| Progression-free Survival (PFS) | PFS was defined as the length of time from the start of the study drug (Day 1) to the earlier of death or disease progression by RECIST v1.1, as assessed by the independent centralized radiological review committee. | up to 1138 days | 
| Duration of Response (DOR) | DOR was defined as the time from the first overall response contributing to an objective response (CR or PR) to the earlier of death or first overall response of PD occurring after the first overall response contributing to the objective response. CR: disappearance of all target and non-target lesions and no appearance of any new lesions. Any pathological lymph nodes (whether target or non-target) must have a reduction in the short axis to <10 millimeters (mm). PR: complete disappearance or at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference the baseline sum diameters, no new lesions, and no progression of non-target lesions. Response was based on review of scans by an independent centralized radiological review committee. Response was confirmed | up to 1075 days | 
| Overall Survival | Overall survival was defined as the length of time from the start of the study drug (Day 1) until the date of death due to any cause. | up to 1610 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Urothelial carcinoma, fibroblast growth factor receptor (FGFR), FGF/FGFR alterations, fibroblast growth factor (FGF)