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)

Status

Active, not recruiting

Phases

Phase 2

Study type

Interventional

Source

EU CTR

Registry ID

EUCTR2019-000721-50-ES

Enrollment

372

Registered

2019-11-11

Start date

2019-12-16

Completion date

Unknown

Last updated

2023-10-23

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Male and female participants at least 18 years of age who have untreated metastatic or unresectable urothelial carcinoma. MedDRA version: 20.0 Level: PT Classification code 10005003 Term: Bladder cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Interventions

Product Code: INCB054828 Pharmaceutical Form: Tablet INN or Proposed INN: pemigatinib CAS Number: 1513857-77-6 Current Sponsor code: INCB054828 Other descriptive name: INCB054828 Concentration unit: m

Eligibility

Sex/Gender

All

Inclusion criteria

Inclusion criteria: 1. Men and women, aged 18 years and older. 2. Histologically documented metastatic or unresectable UC; may include primary site from bladder, ureters, upper tract, renal pelvis, urethra, or urachus. Both transitional cell and mixed transitional cell histologies are allowed, provided urothelial component is = 50%. Note: Participants with non-UC of the urinary tract are not allowed. 3. Have at least 1 measurable target lesion per RECIST v1.1 as assessed by the local site investigator/radiologist. Eligibility for chemotherapy is defined as meeting either criterion #4 OR #5 as described below. 4. Cisplatin ineligibility, defined by the presence of one of the following criteria: a. Creatinine clearance of =65 years) yes F.1.3.1 Number of subjects for this age range 110

Exclusion criteria

Exclusion criteria: 1. Prior receipt of a selective FGFR inhibitor (eg, erdafitinib, rogaratinib, dovitinib, vofatamab) for any indication or reason. 2. 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. 3. Receipt of anticancer medications or investigational drugs for unresectable and/or metastatic disease (not including adjuvant/neo-adjuvant treatment with platinumcontaining chemotherapy completed = 12 months prior to the start of treatment for this study). 4. Concurrent anticancer therapy (eg, chemotherapy, radiation therapy, surgery, immunotherapy, biologic therapy, hormonal therapy, investigational therapy, tumor embolization), except for treatment allowed per protocol. 5. Has disease that is suitable for local therapy administered with curative intent. 6. Has tumor with any neuroendocrine or small cell component. 7. Current evidence of clinically significant corneal (including but not limited to bullous/band keratopathy, corneal abrasion, inflammation/ulceration, and keratoconjunctivitis, etc) or retinal disorder (including but not limited to macular/retinal degeneration, diabetic retinopathy, retinal detachment, etc) as confirmed by ophthalmologic examination. 8. 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. Participants must have recovered from all radiation-related toxicities and must not require corticosteroids. 9. Has CNS 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. Any signs (eg, radiologic) or symptoms of CNS metastases must be stable for at least 4 weeks before starting study treatment.

Design outcomes

Primary

Measure	Time frame
Main Objective: To evaluate and compare PFS in participants treated with pemigatinib in combination with pembrolizumab (Treatment Group A) and pemigatinib alone (Treatment Group B) versus SOC (Treatment Group C). Differences in PFS will be evaluated hierarchically, and the comparison between pemigatinib in combination with pembrolizumab (Treatment Group A) and SOC (Treatment Group C) will be evaluated first, and if significant difference is detected, a second comparison will be made in PFS between pemigatinib alone (Treatment Group B) and SOC (Treatment Group C). Hypothesis: The combination of pembrolizumab plus pemigatinib has superior PFS as compared with SOC. Contribution of pemigatinib alone to combination will be tested by comparing Treatment Groups A and C and Treatment Groups B and C.;Secondary Objective: - To evaluate and compare the efficacy of the 3 treatment groups with respect to OS. - To evaluate and compare the efficacy of the 3 treatment groups with respect to overall tumor response and DOR. - To evaluate the safety of the 3 treatment groups. - To evaluate changes from baseline in patient-reported outcomes.;Primary end point(s): Progression-free survival, defined as the time from randomization date until the date of disease progression (as measured by BICR per RECIST v1.1) or death due to any cause, whichever occurs first.;Timepoint(s) of evaluation of this end point: The schedule for efficacy assessments will be at screening (this will be considered the baseline scan), every 9 weeks (every 3 cycles) from date of randomization until 1 year, then every 12 weeks (every 4 cycles) thereafter, and then at EOT (if applicable). Please refer to the schedule of activities reported in table 4 of the protocol.	—

Measure

Time frame

Main Objective: To evaluate and compare PFS in participants treated with pemigatinib in combination with pembrolizumab (Treatment Group A) and pemigatinib alone (Treatment Group B) versus SOC (Treatment Group C). Differences in PFS will be evaluated hierarchically, and the comparison between pemigatinib in combination with pembrolizumab (Treatment Group A) and SOC (Treatment Group C) will be evaluated first, and if significant difference is detected, a second comparison will be made in PFS between pemigatinib alone (Treatment Group B) and SOC (Treatment Group C). Hypothesis: The combination of pembrolizumab plus pemigatinib has superior PFS as compared with SOC. Contribution of pemigatinib alone to combination will be tested by comparing Treatment Groups A and C and Treatment Groups B and C.;Secondary Objective: - To evaluate and compare the efficacy of the 3 treatment groups with respect to OS. - To evaluate and compare the efficacy of the 3 treatment groups with respect to overall tumor response and DOR. - To evaluate the safety of the 3 treatment groups. - To evaluate changes from baseline in patient-reported outcomes.;Primary end point(s): Progression-free survival, defined as the time from randomization date until the date of disease progression (as measured by BICR per RECIST v1.1) or death due to any cause, whichever occurs first.;Timepoint(s) of evaluation of this end point: The schedule for efficacy assessments will be at screening (this will be considered the baseline scan), every 9 weeks (every 3 cycles) from date of randomization until 1 year, then every 12 weeks (every 4 cycles) thereafter, and then at EOT (if applicable). Please refer to the schedule of activities reported in table 4 of the protocol.

—

Secondary

Measure	Time frame
Secondary end point(s): - Overall survival, defined the time from the date of randomization until death due to any cause. - Objective response rate, defined as the proportion of participants with best overall response of CR or PR determined by BICR per RECIST v1.1. - Duration of response, defined as the time from the date of the first assessment of CR or PR until the date of the first disease progression per BICR per RECIST v1.1 or death, whichever occurs first. - Safety and tolerability of pemigatinib with or without pembrolizumab and SOC will be assessed by evaluating the frequency, duration and severity of AEs, physical examination findings, vital sign changes, and clinical laboratory assessments. - Patient-reported outcome scales (ie, EORTC QLQ-C30, EQ-5D-5L) at each timepoint and change from baseline to each timepoint.;Timepoint(s) of evaluation of this end point: The schedule for efficacy assessments will be at screening (this will be considered the baseline scan), every 9 weeks (every 3 cycles) from date of randomization until 1 year, then every 12 weeks (every 4 cycles) thereafter, and then at EOT (if applicable). Adverse events (CTCAE v4.03) will be monitored from the time the participant signs the ICF until at least 30 days for after the last dose of study treatment. A comprehensive eye examination should be performed by a qualified ophthalmologist at screening on all participants, once every 3 cycles (± 7 days) for participants randomized to Treatment Groups A and B only, at EOT for all participants, and as clinically indicated. Please refer to the schedule of activities reported in table 4 of the protocol.	—

Measure

Time frame

Secondary end point(s): - Overall survival, defined the time from the date of randomization until death due to any cause. - Objective response rate, defined as the proportion of participants with best overall response of CR or PR determined by BICR per RECIST v1.1. - Duration of response, defined as the time from the date of the first assessment of CR or PR until the date of the first disease progression per BICR per RECIST v1.1 or death, whichever occurs first. - Safety and tolerability of pemigatinib with or without pembrolizumab and SOC will be assessed by evaluating the frequency, duration and severity of AEs, physical examination findings, vital sign changes, and clinical laboratory assessments. - Patient-reported outcome scales (ie, EORTC QLQ-C30, EQ-5D-5L) at each timepoint and change from baseline to each timepoint.;Timepoint(s) of evaluation of this end point: The schedule for efficacy assessments will be at screening (this will be considered the baseline scan), every 9 weeks (every 3 cycles) from date of randomization until 1 year, then every 12 weeks (every 4 cycles) thereafter, and then at EOT (if applicable). Adverse events (CTCAE v4.03) will be monitored from the time the participant signs the ICF until at least 30 days for after the last dose of study treatment. A comprehensive eye examination should be performed by a qualified ophthalmologist at screening on all participants, once every 3 cycles (± 7 days) for participants randomized to Treatment Groups A and B only, at EOT for all participants, and as clinically indicated. Please refer to the schedule of activities reported in table 4 of the protocol.

—

Countries

Australia, Austria, Belgium, Bulgaria, Canada, Finland, France, Germany, Hungary, Ireland, Israel, Italy, Poland, Portugal, Spain, United Kingdom, United States

Contacts

Public ContactClinical Trials Information

Incyte Corporation

RA@incyte.com13024252734

Outcome results

None listed

Source: EU CTR (via WHO ICTRP) · Data processed: Feb 4, 2026