Antineoplastic Agents

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Pembrolizumab

Docetaxel

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Antimitotic Agents

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Participants will be screened based on Fibroblast Growth Factor Receptor Inhibitor Clinical Trial Assay (FGFRi CTA) to determine molecular eligibility and participants who meet molecular eligibility criteria will be eligible for full study screening. Participants enrolled in the study (treated with prior anti-programmed cell death protein PD-\[L\] 1 agent) will swallow erdafitinib tablets orally at a starting dose of 8 milligram (mg), once daily for 21 days in a 21-day cycle until disease progression, intolerable toxicity, withdrawal of consent or decision by the investigator to discontinue treatment. Dose adjustment are based on phosphate level and observed toxicity (adverse events \[AEs\]). Participants who enter in Long-term extension (LTE) phase will continue to receive the erdafitinib tablet as per investigator's decision.

Participants will be screened based on FGFRi CTA to determine molecular eligibility and participants who meet molecular eligibility criteria will be eligible for full study screening. Participants enrolled in the study (treated with prior anti-PD-\[L\] 1 agent) will receive vinflunine 320 milligram per meter square (mg/m\^2) as a 20-minute intravenous infusion once every 3 weeks or docetaxel 75 mg/m\^2 as a 1 hour intravenous infusion every 3 weeks. Treatment with either agent (choice of investigator) will be administered until disease progression, intolerable toxicity, withdrawal of consent or decision by the investigator to discontinue treatment. Dose adjustments are based on observed toxicities. Participants who enter in LTE phase will continue to receive Vinflunine or Docetaxel until the participant can commercially receive chemotherapy within the local healthcare system.

Participants will be screened based on FGFRi CTA to determine molecular eligibility and participants who meet molecular eligibility criteria will be eligible for full study screening. Participants enrolled in the study (no prior treatment with anti-PD-\[L\] 1 agent) will swallow erdafitinib tablets orally at a starting dose of 8 mg, once daily for 21 days in a 21-day cycle until disease progression, intolerable toxicity, withdrawal of consent or decision by the investigator to discontinue treatment. Dose adjustments are based on phosphate level and observed toxicity (AEs). Participants who enter in LTE phase will continue to receive the erdafitinib tablet as per investigator's decision.

Participants will be screened based on FGFRi CTA to determine molecular eligibility and participants who meet molecular eligibility criteria will be eligible for full study screening. Participants enrolled in the study (no prior treatment with anti-PD-\[L\] 1 agent) will receive pembrolizumab 200 mg as a 30-minute intravenous infusion once every 3 weeks, until disease progression, intolerable toxicity, withdrawal of consent or decision by the investigator to discontinue treatment. Dose adjustments are based on observed toxicities. Participants who enter in LTE phase will continue to receive the pembrolizumab until 2 years after the first dose of pembrolizumab (at start of study) or until the participant can commercially receive pembrolizumab within the local healthcare system, whichever comes first.

Participants will swallow erdafitinib tablets orally at a starting dose of 8 mg.

Erdafitinib

Participants will receive vinflunine 320 mg/m\^2 as a 20-minute intravenous infusion.

Vinflunine

Participants will receive docetaxel 75 mg/m\^2 as a 1 hour intravenous infusion.

Participants will receive pembrolizumab 200 mg as a 30-minute intravenous infusion.

FGFRi CTA will be used to determine molecular eligibility.

Fibroblast Growth Factor Receptor inhibitor Clinical Trial Assay (FGFRi CTA)

Janssen Research & Development, LLC Clinical Trial

The purpose of this study is to evaluate efficacy of erdafitinib versus chemotherapy or pembrolizumab in participants with advanced urothelial cancer harboring selected fibroblast growth factor receptor (FGFR) aberrations who have progressed after 1 or 2 prior treatments, at least 1 of which includes an anti-programmed death ligand 1(PD-\[L\]1) agent (cohort 1) or 1 prior treatment not containing an anti-PD-(L) 1 agent (cohort 2).

A study of erdafitinib versus standard of care, consisting of chemotherapy (docetaxel or vinflunine) or anti-PD-(L) 1 agent pembrolizumab, in participants with advanced urothelial cancer and selected FGFR aberrations who have progressed on or after 1 or 2 prior treatments, at least 1 of which includes an anti-PD-(L) 1 agent (cohort 1) or 1 prior treatment not containing an anti-PD-(L) 1 agent (cohort 2). It will consist of screening, treatment phase (from randomization until disease progression, intolerable toxicity, withdrawal of consent or decision by investigator to discontinue treatment, post-treatment follow-up (from end-of-treatment to participants death, withdraws consent, lost to follow-up study completion for the respective cohort, whichever comes first). The study will have long term extension (LTE) period after clinical cutoff date is achieved for final analysis of each cohort and participants eligible in the opinion of the investigator, will continue to benefit from the study intervention. Efficacy, pharmacokinetics, biomarkers, patient reported outcomes, medical resource utilization and safety will be assessed.

A Study of Erdafitinib Compared With Vinflunine or Docetaxel or Pembrolizumab in Participants With Advanced Urothelial Cancer and Selected Fibroblast Growth Factor Receptor (FGFR) Gene Aberrations

A Phase 3 Study of Erdafitinib Compared With Vinflunine or Docetaxel or Pembrolizumab in Subjects With Advanced Urothelial Cancer and Selected FGFR Gene Aberrations

Overall survival is measured from the date of randomization to the date of the participant's death. If the participant is alive or the vital status is unknown, the participant will be censored at the date the participant was last known to be alive.

PFS is defined as duration in days from date of randomization to disease progression date (assessed per Response Evaluation Criteria in Solid Tumors Version 1.1 \[RECIST v1.1\] by investigator) or relapse from CR or death, whichever is reported first. RECIST 1.1, progressive disease is defined as a 20 percent (%) increase in the sum of diameters of all target lesions and a minimum absolute increase of 5 millimeter (mm) in the sum. CR is defined as disappearance of all target lesions, non-target lesions and normalization of tumor marker level.

ORR is defined as the proportion of participants who achieve CR (CR; disappearance of all target lesions and disappearance of all non-target lesions and normalization of tumor marker level) or partial response (PR; at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters), as assessed per RECIST v1.1 by the investigator.

The FACT-Bl consists of 36 core items, with 5-point Likert response scales, covering 5 primary domains: Physical well-being, social/family well-being, emotional well-being, functional well-being, and bladder symptom subscale. The answer scales range from "Not at all (score=0)" to "very much (score=4)" to assess the meaningful significant symptom deterioration.

The PGIS is a single question regarding the participant report of disease severity. Participants will be asked that ''considering all aspects of your bladder cancer symptoms right now, would you say your bladder cancer symptoms are none, mild, moderate, severe, or very severe?" The PGIS is an anchor question that will be used to establish the magnitude of meaningful change in this study by assessing disease severity.

European Quality of Life 5 Dimensions (EQ-5D) visual analog scale (VAS) is a 20 centimeter (cm) vertical VAS with scores ranging from 0 (worst imaginable health) to 100 (perfect health). A higher score indicates an improvement in health in the Health Status Index.

The EuroQol-5 is a five dimensional health state classification. Each dimension is assessed on a 3-point ordinal scale (1=no problems, 2=some problems, 3=extreme problems). The responses to the five EQ-5D dimensions were scored using a utility-weighted algorithm to derive an EQ-5D health status index score between 0 to 1, with 1.00 indicating "full health" and 0 representing dead.

DOR for responders is defined as duration in days from the date of initial documentation of a response to the date of first documented evidence of progressive disease (PD) or relapse for participants who experience CR (CR; disappearance of all target lesions and disappearance of all non-target lesions and normalization of tumor marker level) during the study or death.

An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study.

CL/F is the oral clearance; that is clearance based on oral bioavailability of erdafitinib.

AUC(0-t) is the area under the plasma concentration-time curve from time zero to any time 't' of erdafitinib.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Study of Erdafitinib Compared With Vinflunine or Docetaxel or Pembrolizumab in Participants With Advanced Urothelial Cancer and Selected Fibroblast Growth Factor Receptor (FGFR) Gene Aberrations	NCT03390504	Urothelial Canc...	Erdafitinib Vinflunine Docetaxel Pembrolizumab Fibroblast Grow...	18 Years -	Janssen Research & Development, LLC
A Study of Erdafitinib Compared With Vinflunine or Docetaxel or Pembrolizumab in Participants With Advanced Urothelial Cancer and Selected Fibroblast Growth Factor Receptor (FGFR) Gene Aberrations	NCT03390504	Urothelial Canc...	Erdafitinib Vinflunine Docetaxel Pembrolizumab Fibroblast Grow...	18 Years -	Janssen Research & Development, LLC
A Study of Erdafitinib Compared With Vinflunine or Docetaxel or Pembrolizumab in Participants With Advanced Urothelial Cancer and Selected Fibroblast Growth Factor Receptor (FGFR) Gene Aberrations	NCT03390504	Urothelial Canc...	Erdafitinib Vinflunine Docetaxel Pembrolizumab Fibroblast Grow...	18 Years -	Janssen Research & Development, LLC
A Study of Erdafitinib Compared With Vinflunine or Docetaxel or Pembrolizumab in Participants With Advanced Urothelial Cancer and Selected Fibroblast Growth Factor Receptor (FGFR) Gene Aberrations	NCT03390504	Urothelial Canc...	Erdafitinib Vinflunine Docetaxel Pembrolizumab Fibroblast Grow...	18 Years -	Janssen Research & Development, LLC

Spots Global Cancer Trial Database for fibroblast growth factor receptor inhibitor clinical trial assay (fgfri cta)