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)
- Conditions
- Male and female participants at least 18 years of age who have untreated metastatic or unresectable urothelial carcinoma.MedDRA version: 20.0Level: PTClassification code 10005003Term: Bladder cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2019-000721-50-PL
- Lead Sponsor
- Incyte Corporation
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 372
1. Men and women, aged 18 years and older at the time of signing the informed consent;.a legally minor participant from Japan needs written parental or legal quardian`s consent.
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 < 60 mL/min but = 30 mL/min (measured by the Cockcroft-Gault formula or 24-hour urine).
b. ECOG performance status 2 (within 7 days prior to randomization).
c. = Grade 2 audiometric hearing loss (25 db in 2 consecutive wave ranges; CTCAE v5).
d. New York Heart Association Class III heart failure.
e. = Grade 2 peripheral neuropathy (CTCAE v5).
OR
5. Ineligibility to receive any platinum-based chemotherapy (ie, ineligible for cisplatin and carboplatin), defined as ECOG performance status 2 (within 7 days prior to
randomization) AND at least one of the following:
a. Documented visceral metastatic disease (due to poor prognosis and lack of benefit)
b. Creatinine clearance of < 60 mL/min but = 30 mL/min (measured by the Cockcroft-Gault formula or 24-hour urine).
c. = Grade 2 audiometric hearing loss (25 db in 2 consecutive wave ranges; CTCAE v5).
d. = Grade 2 peripheral neuropathy (CTCAE v5).
e. Other reason, identified on the eCRF, for the participant being unable to receive carboplatin safely. Additional criteria for platinum ineligibility will be considered and allowed on a case-by-case basis, following consultation with the sponsor.
6.Must have known FGFR3 mutation or rearrangement (participant can
be randomized based on a local report, but this will need to be
retrospectively confirmed by the sponsor's central laboratory; see
Appendix E). See Section 8.7.1 for details on tumor tissue requirements.
Note: Participants with gene amplifications only are excluded
7. Local or central laboratory test result of PD-L1 is mandatory at
screening. Participants can be randomized based on a local genomics
report, but this will need to be retrospectively confirmed by the
sponsor's central laboratory. If local result is not available, formalinfixed,
paraffin-embedded tissue blocks or slides must be sent to the
sponsor's central laboratory. Formalin-fixed, paraffin-embedded tissue
blocks are preferred to slides. If submitting unstained cut slides, newly
cut slides should be submitted to the testing laboratory within 30 days
from the date slides are cut (see Section 8.7.1 for details on tumor tissue
requirements). Note: In the event the participant does not have local PD-L1 results or
the sample is not evaluable for PD-L1, the participant will not be eligible.
If a local result is available and the participant is randomized, but the
sample fails or the local result is not confirmed by the central laboratory,
the site should contact the medical monitor.
8. Have received no prior systemic chemotherapy for metastatic or
unresectable UC except:
a. Adjuvant platinum-based chemotherapy, following radical cystectomy,
with recur
1. Prior receipt of a selective FGFR inhibitor (eg, erdafitinib, rogaratinib, infigratinib,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.= 18 months prior to the start of treatment for this study.
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 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.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method