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

Overall survival was measured from the date of randomization to the date of the participant's death.

PFS was defined as the time from the date of randomization to the date of disease progression or relapse from complete response (CR) based on investigator assessment using RECIST v 1.1, or death due to any cause, whichever occurred first. As per RECIST v 1.1, CR was defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must had reduction in the short axis to less than (<) 10 millimeters (mm). Progressive disease (PD) was defined as at least 20 percent (%) increase in the sum of diameters of measured lesions taking as references the smallest sum of diameters recorded on study (including baseline) and an absolute increase of greater than or equal to (>=) 5 mm or appearance of at least 1 new lesion.

ORR was defined as the percentage of participants who achieved CR or partial response (PR) as determined by investigator per RECIST v1.1. CR was defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must had reduction in the short axis to <10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

The FACT-Bl consisted of 39 items, with 5-point Likert scales, covering 5 primary domains: physical well-being, social/family well-being, emotional well-being, functional well-being and additional concerns for participants with bladder cancer. The response options ranged from 0 to 4 where, 0='Not at all" and 4= "very much." FACT-Bl total score ranged from 0 (worst) to 156 (best). The higher the score, the better the quality of life (QOL). The baseline value was defined as the value collected at the time closest to but prior to the randomization.

Time until symptom deterioration was defined as the first time to increase in urinary bladder cancer symptoms score from the day of randomization beyond a meaningful change threshold compared to baseline. The urinary bladder cancer symptom score was subset of FACT-Bl which included 3 items related to urinary symptoms, 5-point Likert scale. Response options ranged from 0 to 4, 0 = Not at all, 1= A little bit, 2= Somewhat, 3=Quite a bit, 4 = Very much. A response of 0 indicated no symptoms and 4 indicated severe symptoms. Total sum scores ranged from 0 to 12, higher scores indicate relatively poor quality of life.

The PGI-S was a single item patient-reported measure assessing participants' impression of severity in bladder cancer symptoms. It uses a 4-point Likert scale as follows: symptoms are: 0-"absent (no symptoms)", 1-"mild", 2-"moderate", 3="severe" and 4= "very severe". Percentage of participants with shift from baseline in PGIS score were reported. A negative shift from baseline in PGIS score indicated Improvement and positive shift from baseline in PGIS score indicated Worsening. The baseline value was defined as the value collected at the time closest to but prior to the randomization.

The EQ-5D-5L was a generic measure of health status. The EQ-5D-5L was a 5-item questionnaire that assessed 5 domains included mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Health utility values generated from the EQ-5D generally range from 0 (a state as bad as being dead) to 1 (full health), with higher scores indicating better QoL. The EQ visual analog scale (VAS) recorded the patient's self-rated health on a VAS, ranged from 0 (worst imaginable health state) to 100 (best imaginable health state), with higher scores indicating better QoL. The baseline value was defined as the value collected at the time closest to but prior to the randomization.

The EQ-5D-5L was a generic measure of health status. The EQ-5D-5L was a 5-item questionnaire that assessed 5 domains included mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Health utility values generated from the EQ-5D generally range from 0 (a state as bad as being dead) to 1 (full health), with higher scores indicating better QoL. The EQ VAS recorded the patient's self-rated health on a VAS, ranged from 0 (worst imaginable health state) to 100 (best imaginable health state), with higher scores indicating better QoL. The baseline value was defined as the value collected at the time closest to but prior to the randomization.

DOR was defined as time from the date of initial documentation of an overall response (CR or PR) to the date of first documented evidence of progressive disease (PD) (or relapse for participants who experience CR) or death. As per RECIST Version 1.1: CR was defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must had reduction in the short axis to <10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. PD was defined as at least 20% increase in the sum of diameters of measured lesions taking as references the smallest sum of diameters recorded on study (including baseline) and an absolute increase of >=5 mm or appearance of at least 1 new lesion.

An adverse event (AE) was any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the intervention. TEAEs were the events between first dose of study drug and up to 30 days after last dose or before start of new anticancer therapy, whichever occurred first. All TEAEs including serious and non-serious events were reported in this outcome measure.

Hematology parameters included: hemoglobin, platelet count, white blood cell (WBC) count, and absolute neutrophil count (ANC). According to national cancer institute (NCI)-common terminology criteria for adverse events (CTCAE) version 4.03: Grade 1= mild, Grade 2= moderate, Grade 3= severe, Grade 4= life-threatening, urgent intervention indicated, Grade 5= death related to AE and Grade 0= normal. In this outcome measure number of participants with shifts from baseline (BL) Grade <= 2 to Grade >=3 post-baseline in any of hematology parameters are reported. The baseline value for safety assessment was defined as the value collected at the time closest to, but prior to, the administration of the first dose of study drug. Only those categories in which at least one participant had data were reported in this outcome measure.

Chemistry parameters included: albumin, alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin, chloride, creatinine, bicarbonate, corrected calcium, magnesium, potassium, sodium, serum phosphate, serum parathyroid hormone. According to NCI-CTCAE version 4.03: Grade 1= mild, Grade 2= moderate, Grade 3= severe, Grade 4= life-threatening, urgent intervention indicated, Grade 5= death related to AE and Grade 0= normal. In this outcome measure number of participants with shifts from baseline (BL) Grade <= 2 to Grade >=3 post-baseline in any of chemistry parameters are reported. The baseline value for safety assessment was defined as the value collected at the time closest to, but prior to, the administration of the first dose of study drug. Only those categories in which at least one participant had data were reported in this outcome measure.

Number of participants with abnormalities in ECG parameters were reported. The ECG variables included heart rate, RR interval, PR interval, QRS interval, QT interval and QT corrected according to Fridericia's formula (QTcF). ECG abnormality criteria include: Heart rate: Low <50 beats per minute (bpm); High > 100 bpm, RR interval: Low < 600 milliseconds (ms); High > 1000 ms, QT interval: High > 500 ms, QTc interval: High > (450 ms for males, 470 ms for females); increase to >500 ms.

Changes from baseline in vital signs (weight) was reported. The baseline value for safety assessment was defined as the value collected at the time closest to, but prior to, the administration of the first dose of study drug.

Number of participants with shift from baseline to worst post-baseline in Amsler grid test was reported. Baseline and post-baseline visit findings included normal, abnormal CS (clinically significant) and abnormal NCS (not clinically significant). Clinical significance was determined by investigator's assessment. The baseline value for safety assessment was defined as the value collected at the time closest to, but prior to, the administration of the first dose of study drug. Only categories in which at least one participant had data for worsening post-baseline measurement was reported.

Number of participants with shift from baseline to worst post-baseline in visual acuity (VA) was reported. Worst post-baseline was defined as the visual acuity value that resulted in the largest change from baseline value for either eye. Baseline value was considered for the eye that reported the worst-post baseline value. Baseline and post-baseline visit visual acuity findings included: <= 20/30, >20/30 to <= 20/40, >20/40 to <= 20/80, >20/80 to <= 20/120, >20/120 to <= 20/160, >20/160 to <= 20/200, >20/200. The baseline value for safety assessment was defined as the value collected at the time closest to, but prior to, the administration of the first dose of study drug. Only categories in which at least one participant had data for worsening in visual acuity from baseline value to worst post-baseline measurement was reported.

Number of participants with shift from baseline to worst post-baseline in optical coherence tomography for subretinal fluid was reported. At the baseline visit, findings may have been absent or present/visible. At all post-baseline visits, findings were compared to baseline and results may have been increased, decreased, stable or resolved. The baseline value for safety assessment was defined as the value collected at the time closest to, but prior to, the administration of the first dose of study drug. Only category (shift from absent at baseline to increased at post-baseline) in which at least one participant had data for worsening post-baseline measurement was reported.

Number of participants with shift from baseline to worst post-baseline in optical coherence tomography for RPE elevation was reported. At the baseline visit, findings may have been absent or present/visible. At all post-baseline visits, findings were compared to baseline and results may have been increased, decreased, stable or resolved. The baseline value for safety assessment was defined as the value collected at the time closest to, but prior to, the administration of the first dose of study drug. Only categories in which at least one participant had data for worsening post-baseline measurement was reported.

Number of participants with shift from baseline to worst post-baseline in slit lamp biomicroscopy examination for retinal assessment was reported. Baseline and post-baseline visit findings included normal, abnormal CS and abnormal NCS. Clinical significance was determined by investigator's assessment. The baseline value for safety assessment was defined as the value collected at the time closest to, but prior to, the administration of the first dose of study drug. Only categories in which at least one participant had data for worsening post-baseline measurement was reported.

Clearance was a measure of the rate at which a drug was metabolized or eliminated by normal biological processes.

Area under the plasma concentration time-curve from time zero to the time t (AUC[0-t]) was reported.