Trial Outcomes & Findings for An Efficacy and Safety Study of Erdafitinib (JNJ-42756493) in Participants With Urothelial Cancer (NCT NCT02365597)

Last Updated: 2025-11-12

Results Overview

Cmax is the maximum observed plasma concentration of 1-OH-Midazolam (midazolam metabolite) alone or in combination with erdafitinib.

Recruitment status

ACTIVE_NOT_RECRUITING

Study phase

PHASE2

Target enrollment

239 participants

Primary outcome timeframe

Cycle 1 Day -2 (predose) up to Day 13 post dose (each cycle length=28 days)

Results posted on

2025-11-12

Participant Flow

Participant milestones

Participant milestones
Measure	Main Study: Regimen 1: Erdafitinib 10 Milligrams (mg)/ 12 mg Participants received single dose of erdafitinib 10 mg tablet, orally, once daily, starting from Day 1 through Day 7 and from Day 15 through Day 21 and so on, that is 7-day on and off in each subsequent 28-day cycles starting from Cycle 1. Based on serum phosphate (PO4) levels, there was an option to up-titrate erdafitinib dose to 12 mg, orally, once daily starting from Cycle 2 Day 1 until disease progression, unacceptable toxicity, or any other reason for treatment discontinuation.	Main Study: Regimen 2: Erdafitinib 6 mg/ 8 mg Participants received single dose of erdafitinib 6 mg tablet, orally, once daily, starting from Day 1 through Day 28 in each subsequent 28-day cycles starting from Cycle 1. Based on serum PO4 levels, there was an option to up-titrate erdafitinib dose to 8 mg, orally, once daily starting from Cycle 2 Day 1 until disease progression, unacceptable toxicity, or any other reason for treatment discontinuation.	Main Study: Regimen 3: Erdafitinib 8 mg/ 9 mg Participants received single dose of erdafitinib 8 mg tablet, orally, once daily, starting from Day 1 through Day 28 in each subsequent 28-day cycles starting from Cycle 1. Based on serum PO4 levels, there was an option to up-titrate erdafitinib dose to 9 mg, orally, once daily starting from Cycle 1 Day 15 until disease progression, unacceptable toxicity, or any other reason for treatment discontinuation.	Drug-Drug Interaction (DDI) Sub-study: Midazolam 2.5 mg + Metformin 1000 mg + Erdafitinib 8/9 mg Participants received pretreatment with single doses of midazolam 2.5 mg syrup orally on Day -2 and metformin 1000 mg tablet orally on Day -1 along with erdafitinib 8 mg tablet, orally, on 28-day cycles starting from Cycle 1 Day 1 to Day 15 (or up-titrated to 9 mg on Day 15 based on Day 14 serum PO4 levels) until disease progression, unacceptable toxicity, or any other reason for treatment discontinuation.
Overall Study STARTED	33	79	102	25
Overall Study Treated (Safety Analysis Set)	33	78	101	25
Overall Study COMPLETED	31	62	83	6
Overall Study NOT COMPLETED	2	17	19	19

Reasons for withdrawal

Reasons for withdrawal
Measure	Main Study: Regimen 1: Erdafitinib 10 Milligrams (mg)/ 12 mg Participants received single dose of erdafitinib 10 mg tablet, orally, once daily, starting from Day 1 through Day 7 and from Day 15 through Day 21 and so on, that is 7-day on and off in each subsequent 28-day cycles starting from Cycle 1. Based on serum phosphate (PO4) levels, there was an option to up-titrate erdafitinib dose to 12 mg, orally, once daily starting from Cycle 2 Day 1 until disease progression, unacceptable toxicity, or any other reason for treatment discontinuation.	Main Study: Regimen 2: Erdafitinib 6 mg/ 8 mg Participants received single dose of erdafitinib 6 mg tablet, orally, once daily, starting from Day 1 through Day 28 in each subsequent 28-day cycles starting from Cycle 1. Based on serum PO4 levels, there was an option to up-titrate erdafitinib dose to 8 mg, orally, once daily starting from Cycle 2 Day 1 until disease progression, unacceptable toxicity, or any other reason for treatment discontinuation.	Main Study: Regimen 3: Erdafitinib 8 mg/ 9 mg Participants received single dose of erdafitinib 8 mg tablet, orally, once daily, starting from Day 1 through Day 28 in each subsequent 28-day cycles starting from Cycle 1. Based on serum PO4 levels, there was an option to up-titrate erdafitinib dose to 9 mg, orally, once daily starting from Cycle 1 Day 15 until disease progression, unacceptable toxicity, or any other reason for treatment discontinuation.	Drug-Drug Interaction (DDI) Sub-study: Midazolam 2.5 mg + Metformin 1000 mg + Erdafitinib 8/9 mg Participants received pretreatment with single doses of midazolam 2.5 mg syrup orally on Day -2 and metformin 1000 mg tablet orally on Day -1 along with erdafitinib 8 mg tablet, orally, on 28-day cycles starting from Cycle 1 Day 1 to Day 15 (or up-titrated to 9 mg on Day 15 based on Day 14 serum PO4 levels) until disease progression, unacceptable toxicity, or any other reason for treatment discontinuation.
Overall Study Lost to Follow-up	0	1	0	1
Overall Study Withdrawal by Subject	1	8	5	1
Overall Study Sponsor's decision	1	3	13	0
Overall Study Other	0	4	0	0
Overall Study Enrolled but not treated	0	1	1	0
Overall Study Ongoing	0	0	0	17

Baseline Characteristics

An Efficacy and Safety Study of Erdafitinib (JNJ-42756493) in Participants With Urothelial Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Main Study: Regimen 1: Erdafitinib 10 Milligrams (mg)/ 12 mg n=33 Participants Participants received single dose of erdafitinib 10 mg tablet, orally, once daily, starting from Day 1 through Day 7 and from Day 15 through Day 21 and so on, that is 7-day on and off in each subsequent 28-day cycles starting from Cycle 1. Based on serum phosphate (PO4) levels, there was an option to up-titrate erdafitinib dose to 12 mg, orally, once daily starting from Cycle 2 Day 1 until disease progression, unacceptable toxicity, or any other reason for treatment discontinuation.	Main Study: Regimen 2: Erdafitinib 6 mg/ 8 mg n=78 Participants Participants received single dose of erdafitinib 6 mg tablet, orally, once daily, starting from Day 1 through Day 28 in each subsequent 28-day cycles starting from Cycle 1. Based on serum PO4 levels, there was an option to up-titrate erdafitinib dose to 8 mg, orally, once daily starting from Cycle 2 Day 1 until disease progression, unacceptable toxicity, or any other reason for treatment discontinuation.	Main Study: Regimen 3: Erdafitinib 8 mg/ 9 mg n=101 Participants Participants received single dose of erdafitinib 8 mg tablet, orally, once daily, starting from Day 1 through Day 28 in each subsequent 28-day cycles starting from Cycle 1. Based on serum PO4 levels, there was an option to up-titrate erdafitinib dose to 9 mg, orally, once daily starting from Cycle 1 Day 15 until disease progression, unacceptable toxicity, or any other reason for treatment discontinuation.	Drug-Drug Interaction (DDI) Sub-study: Midazolam 2.5 mg + Metformin 1000 mg + Erdafitinib 8/9 mg n=25 Participants Participants received pretreatment with single doses of midazolam 2.5 mg syrup orally on Day -2 and metformin 1000 mg tablet orally on Day -1 along with erdafitinib 8 mg tablet, orally, on 28-day cycles starting from Cycle 1 Day 1 to Day 15 (or up-titrated to 9 mg on Day 15 based on Day 14 serum PO4 levels) until disease progression, unacceptable toxicity, or any other reason for treatment discontinuation.	Total n=237 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=10 Participants	0 Participants n=10 Participants	0 Participants n=20 Participants	0 Participants n=45 Participants	0 Participants n=44 Participants
Age, Categorical Between 18 and 65 years	11 Participants n=10 Participants	39 Participants n=10 Participants	39 Participants n=20 Participants	11 Participants n=45 Participants	100 Participants n=44 Participants
Age, Categorical >=65 years	22 Participants n=10 Participants	39 Participants n=10 Participants	62 Participants n=20 Participants	14 Participants n=45 Participants	137 Participants n=44 Participants
Age, Continuous	68.6 years STANDARD_DEVIATION 7.98 • n=10 Participants	64.5 years STANDARD_DEVIATION 10.36 • n=10 Participants	66.1 years STANDARD_DEVIATION 10.2 • n=20 Participants	64.8 years STANDARD_DEVIATION 10.35 • n=45 Participants	65.8 years STANDARD_DEVIATION 10.03 • n=44 Participants
Sex: Female, Male Female	11 Participants n=10 Participants	24 Participants n=10 Participants	24 Participants n=20 Participants	10 Participants n=45 Participants	69 Participants n=44 Participants
Sex: Female, Male Male	22 Participants n=10 Participants	54 Participants n=10 Participants	77 Participants n=20 Participants	15 Participants n=45 Participants	168 Participants n=44 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=10 Participants	2 Participants n=10 Participants	2 Participants n=20 Participants	1 Participants n=45 Participants	6 Participants n=44 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	25 Participants n=10 Participants	68 Participants n=10 Participants	75 Participants n=20 Participants	22 Participants n=45 Participants	190 Participants n=44 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	7 Participants n=10 Participants	8 Participants n=10 Participants	24 Participants n=20 Participants	2 Participants n=45 Participants	41 Participants n=44 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	0 Participants n=10 Participants	0 Participants n=10 Participants	0 Participants n=20 Participants	0 Participants n=45 Participants	0 Participants n=44 Participants
Race/Ethnicity, Customized Asian	2 Participants n=10 Participants	11 Participants n=10 Participants	5 Participants n=20 Participants	0 Participants n=45 Participants	18 Participants n=44 Participants
Race/Ethnicity, Customized Black or African American	0 Participants n=10 Participants	2 Participants n=10 Participants	2 Participants n=20 Participants	0 Participants n=45 Participants	4 Participants n=44 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	0 Participants n=10 Participants	0 Participants n=10 Participants	0 Participants n=20 Participants	0 Participants n=45 Participants	0 Participants n=44 Participants
Race/Ethnicity, Customized White	24 Participants n=10 Participants	56 Participants n=10 Participants	75 Participants n=20 Participants	20 Participants n=45 Participants	175 Participants n=44 Participants
Race/Ethnicity, Customized More than one race	0 Participants n=10 Participants	0 Participants n=10 Participants	0 Participants n=20 Participants	3 Participants n=45 Participants	3 Participants n=44 Participants
Race/Ethnicity, Customized Unknown or Not Reported	7 Participants n=10 Participants	7 Participants n=10 Participants	18 Participants n=20 Participants	2 Participants n=45 Participants	34 Participants n=44 Participants
Race/Ethnicity, Customized Other	0 Participants n=10 Participants	2 Participants n=10 Participants	1 Participants n=20 Participants	0 Participants n=45 Participants	3 Participants n=44 Participants
Region of Enrollment AUSTRIA	0 Participants n=10 Participants	2 Participants n=10 Participants	2 Participants n=20 Participants	0 Participants n=45 Participants	4 Participants n=44 Participants
Region of Enrollment BELGIUM	3 Participants n=10 Participants	2 Participants n=10 Participants	4 Participants n=20 Participants	0 Participants n=45 Participants	9 Participants n=44 Participants
Region of Enrollment FRANCE	7 Participants n=10 Participants	9 Participants n=10 Participants	20 Participants n=20 Participants	1 Participants n=45 Participants	37 Participants n=44 Participants
Region of Enrollment GERMANY	0 Participants n=10 Participants	5 Participants n=10 Participants	6 Participants n=20 Participants	0 Participants n=45 Participants	11 Participants n=44 Participants
Region of Enrollment INDIA	0 Participants n=10 Participants	0 Participants n=10 Participants	0 Participants n=20 Participants	3 Participants n=45 Participants	3 Participants n=44 Participants
Region of Enrollment ISRAEL	0 Participants n=10 Participants	2 Participants n=10 Participants	3 Participants n=20 Participants	0 Participants n=45 Participants	5 Participants n=44 Participants
Region of Enrollment ITALY	4 Participants n=10 Participants	12 Participants n=10 Participants	19 Participants n=20 Participants	0 Participants n=45 Participants	35 Participants n=44 Participants
Region of Enrollment MOLDOVA, REPUBLIC OF	0 Participants n=10 Participants	1 Participants n=10 Participants	0 Participants n=20 Participants	0 Participants n=45 Participants	1 Participants n=44 Participants
Region of Enrollment ROMANIA	0 Participants n=10 Participants	1 Participants n=10 Participants	1 Participants n=20 Participants	0 Participants n=45 Participants	2 Participants n=44 Participants
Region of Enrollment RUSSIAN FEDERATION	1 Participants n=10 Participants	7 Participants n=10 Participants	11 Participants n=20 Participants	0 Participants n=45 Participants	19 Participants n=44 Participants
Region of Enrollment SOUTH KOREA	2 Participants n=10 Participants	9 Participants n=10 Participants	3 Participants n=20 Participants	0 Participants n=45 Participants	14 Participants n=44 Participants
Region of Enrollment SPAIN	7 Participants n=10 Participants	8 Participants n=10 Participants	4 Participants n=20 Participants	20 Participants n=45 Participants	39 Participants n=44 Participants
Region of Enrollment TAIWAN	0 Participants n=10 Participants	2 Participants n=10 Participants	2 Participants n=20 Participants	0 Participants n=45 Participants	4 Participants n=44 Participants
Region of Enrollment TURKEY	0 Participants n=10 Participants	0 Participants n=10 Participants	0 Participants n=20 Participants	1 Participants n=45 Participants	1 Participants n=44 Participants
Region of Enrollment UNITED KINGDOM	1 Participants n=10 Participants	5 Participants n=10 Participants	5 Participants n=20 Participants	0 Participants n=45 Participants	11 Participants n=44 Participants
Region of Enrollment UNITED STATES	8 Participants n=10 Participants	13 Participants n=10 Participants	21 Participants n=20 Participants	0 Participants n=45 Participants	42 Participants n=44 Participants

PRIMARY outcome

Timeframe: From Cycle 1 Day 1 up to 6 years 2 months

Population: The population included participants who received at least 1 dose of study drug.

Percentage of participants with best (overall) objective response were reported. Best objective response is defined as the best (overall) objective response a participants achieved during the study in the order of complete response (CR), partial response (PR), stable disease (SD), progressive disease (PD), where CR and PR were confirmed as per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. 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 less than (\<) 10 millimeters (mm). PR was defined as at least a 30 percent (%) decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Responders are participants with BOR of CR or PR.

Outcome measures

Outcome measures
Measure	DDI Study: Metformin 1000 mg + Erdafitinib 8 mg n=78 Participants Participants received single dose of metformin 1000 mg tablet, orally, once daily, starting from Day -1 through Day 14 of Cycle 1 along with erdafitinib 8 mg starting from Day 1 up to Day 15 of Cycle 1 (each cycle length=28 days).	Main Study: Regimen 1: Erdafitinib 10 Milligrams (mg)/ 12 mg n=33 Participants Participants received single dose of erdafitinib 10 mg tablet, orally, once daily, starting from Day 1 through Day 7 and from Day 15 through Day 21 and so on, that is 7-day on and off in each subsequent 28-day cycles starting from Cycle 1. Based on serum phosphate (PO4) levels, there was an option to up-titrate erdafitinib dose to 12 mg, orally, once daily starting from Cycle 2 Day 1 until disease progression, unacceptable toxicity, or any other reason for treatment discontinuation.	Main Study: Regimen 3: Erdafitinib 8 mg/ 9 mg n=101 Participants Participants received single dose of erdafitinib 8 mg tablet, orally, once daily, starting from Day 1 through Day 28 in each subsequent 28-day cycles starting from Cycle 1. Based on serum PO4 levels, there was an option to up-titrate erdafitinib dose to 9 mg, orally, once daily starting from Cycle 1 Day 15 until disease progression, unacceptable toxicity, or any other reason for treatment discontinuation.
Main Study: Percentage of Participants With Best (Overall) Objective Response	34.6 Percentage of Participants	21.2 Percentage of Participants	39.6 Percentage of Participants

PRIMARY outcome

Timeframe: Cycle 1 Day -2 (predose) up to Day 13 post dose

Population: Pharmacokinetic analysis set included all participants who received at least 1 dose of study drug and had at least 1 sample collected during treatment to determine the drug concentration. Here 'N' (number of participants analyzed) signifies number of participants who were evaluable for this outcome measure.

Cmax is the maximum observed plasma concentration of midazolam alone or in combination with erdafitinib.

Outcome measures

Outcome measures
Measure	DDI Study: Metformin 1000 mg + Erdafitinib 8 mg n=22 Participants Participants received single dose of metformin 1000 mg tablet, orally, once daily, starting from Day -1 through Day 14 of Cycle 1 along with erdafitinib 8 mg starting from Day 1 up to Day 15 of Cycle 1 (each cycle length=28 days).	Main Study: Regimen 1: Erdafitinib 10 Milligrams (mg)/ 12 mg n=23 Participants Participants received single dose of erdafitinib 10 mg tablet, orally, once daily, starting from Day 1 through Day 7 and from Day 15 through Day 21 and so on, that is 7-day on and off in each subsequent 28-day cycles starting from Cycle 1. Based on serum phosphate (PO4) levels, there was an option to up-titrate erdafitinib dose to 12 mg, orally, once daily starting from Cycle 2 Day 1 until disease progression, unacceptable toxicity, or any other reason for treatment discontinuation.	Main Study: Regimen 3: Erdafitinib 8 mg/ 9 mg Participants received single dose of erdafitinib 8 mg tablet, orally, once daily, starting from Day 1 through Day 28 in each subsequent 28-day cycles starting from Cycle 1. Based on serum PO4 levels, there was an option to up-titrate erdafitinib dose to 9 mg, orally, once daily starting from Cycle 1 Day 15 until disease progression, unacceptable toxicity, or any other reason for treatment discontinuation.
Drug-Drug Interaction (DDI) Substudy: Maximum Observed Plasma Concentration (Cmax) of Midazolam Alone or in Combination With Erdafitinib	15.4 nanograms per milliliter (ng/mL) Standard Deviation 5.90	18.4 nanograms per milliliter (ng/mL) Standard Deviation 7.32	—

PRIMARY outcome

Timeframe: Cycle 1 Day -2 (predose) up to Day 13 post dose (each cycle length=28 days)

Cmax is the maximum observed plasma concentration of 1-OH-Midazolam (midazolam metabolite) alone or in combination with erdafitinib.

Outcome measures

Outcome measures
Measure	DDI Study: Metformin 1000 mg + Erdafitinib 8 mg n=22 Participants Participants received single dose of metformin 1000 mg tablet, orally, once daily, starting from Day -1 through Day 14 of Cycle 1 along with erdafitinib 8 mg starting from Day 1 up to Day 15 of Cycle 1 (each cycle length=28 days).	Main Study: Regimen 1: Erdafitinib 10 Milligrams (mg)/ 12 mg n=23 Participants Participants received single dose of erdafitinib 10 mg tablet, orally, once daily, starting from Day 1 through Day 7 and from Day 15 through Day 21 and so on, that is 7-day on and off in each subsequent 28-day cycles starting from Cycle 1. Based on serum phosphate (PO4) levels, there was an option to up-titrate erdafitinib dose to 12 mg, orally, once daily starting from Cycle 2 Day 1 until disease progression, unacceptable toxicity, or any other reason for treatment discontinuation.	Main Study: Regimen 3: Erdafitinib 8 mg/ 9 mg Participants received single dose of erdafitinib 8 mg tablet, orally, once daily, starting from Day 1 through Day 28 in each subsequent 28-day cycles starting from Cycle 1. Based on serum PO4 levels, there was an option to up-titrate erdafitinib dose to 9 mg, orally, once daily starting from Cycle 1 Day 15 until disease progression, unacceptable toxicity, or any other reason for treatment discontinuation.
Drug-Drug Interaction (DDI) Substudy: Maximum Observed Plasma Concentration (Cmax) of 1-OH-Midazolam (Midazolam Metabolite) Alone or in Combination With Erdafitinib	4.82 ng/mL Standard Deviation 2.60	5.39 ng/mL Standard Deviation 3.42	—

PRIMARY outcome

Timeframe: Cycle 1 Day -1 (predose) up to Day 14 post dose (each cycle length=28 days)

Cmax is the maximum observed plasma concentration of metformin alone or in combination with erdafitinib

Outcome measures

Outcome measures
Measure	DDI Study: Metformin 1000 mg + Erdafitinib 8 mg n=19 Participants Participants received single dose of metformin 1000 mg tablet, orally, once daily, starting from Day -1 through Day 14 of Cycle 1 along with erdafitinib 8 mg starting from Day 1 up to Day 15 of Cycle 1 (each cycle length=28 days).	Main Study: Regimen 1: Erdafitinib 10 Milligrams (mg)/ 12 mg n=20 Participants Participants received single dose of erdafitinib 10 mg tablet, orally, once daily, starting from Day 1 through Day 7 and from Day 15 through Day 21 and so on, that is 7-day on and off in each subsequent 28-day cycles starting from Cycle 1. Based on serum phosphate (PO4) levels, there was an option to up-titrate erdafitinib dose to 12 mg, orally, once daily starting from Cycle 2 Day 1 until disease progression, unacceptable toxicity, or any other reason for treatment discontinuation.	Main Study: Regimen 3: Erdafitinib 8 mg/ 9 mg Participants received single dose of erdafitinib 8 mg tablet, orally, once daily, starting from Day 1 through Day 28 in each subsequent 28-day cycles starting from Cycle 1. Based on serum PO4 levels, there was an option to up-titrate erdafitinib dose to 9 mg, orally, once daily starting from Cycle 1 Day 15 until disease progression, unacceptable toxicity, or any other reason for treatment discontinuation.
Drug-Drug Interaction (DDI) Substudy: Maximum Observed Plasma Concentration (Cmax) of Metformin Alone or in Combination With Erdafitinib	2687 ng/mL Standard Deviation 1127	2465 ng/mL Standard Deviation 986	—

PRIMARY outcome

Timeframe: Cycle 1 Day -2 (predose) up to Day 13 post dose (each cycle length=28 days)

Tmax is the time to reach the maximum observed plasma concentration of midazolam alone or in combination with erdafitinib.

Outcome measures

Outcome measures
Measure	DDI Study: Metformin 1000 mg + Erdafitinib 8 mg n=22 Participants Participants received single dose of metformin 1000 mg tablet, orally, once daily, starting from Day -1 through Day 14 of Cycle 1 along with erdafitinib 8 mg starting from Day 1 up to Day 15 of Cycle 1 (each cycle length=28 days).	Main Study: Regimen 1: Erdafitinib 10 Milligrams (mg)/ 12 mg n=23 Participants Participants received single dose of erdafitinib 10 mg tablet, orally, once daily, starting from Day 1 through Day 7 and from Day 15 through Day 21 and so on, that is 7-day on and off in each subsequent 28-day cycles starting from Cycle 1. Based on serum phosphate (PO4) levels, there was an option to up-titrate erdafitinib dose to 12 mg, orally, once daily starting from Cycle 2 Day 1 until disease progression, unacceptable toxicity, or any other reason for treatment discontinuation.	Main Study: Regimen 3: Erdafitinib 8 mg/ 9 mg Participants received single dose of erdafitinib 8 mg tablet, orally, once daily, starting from Day 1 through Day 28 in each subsequent 28-day cycles starting from Cycle 1. Based on serum PO4 levels, there was an option to up-titrate erdafitinib dose to 9 mg, orally, once daily starting from Cycle 1 Day 15 until disease progression, unacceptable toxicity, or any other reason for treatment discontinuation.
Drug-Drug Interaction (DDI) Substudy: Time to Reach the Maximum Observed Plasma Concentration (Tmax) of Midazolam Alone or in Combination With Erdafitinib	0.58 Hours Interval 0.45 to 2.0	0.50 Hours Interval 0.47 to 1.08	—

PRIMARY outcome

Timeframe: Cycle 1 Day -2 (predose) up to Day 13 post dose (each cycle length=28 days)

Tmax is the time to reach the maximum observed plasma concentration of 1-OH-Midazolam alone or in combination with erdafitinib.

Outcome measures

Outcome measures
Measure	DDI Study: Metformin 1000 mg + Erdafitinib 8 mg n=22 Participants Participants received single dose of metformin 1000 mg tablet, orally, once daily, starting from Day -1 through Day 14 of Cycle 1 along with erdafitinib 8 mg starting from Day 1 up to Day 15 of Cycle 1 (each cycle length=28 days).	Main Study: Regimen 1: Erdafitinib 10 Milligrams (mg)/ 12 mg n=23 Participants Participants received single dose of erdafitinib 10 mg tablet, orally, once daily, starting from Day 1 through Day 7 and from Day 15 through Day 21 and so on, that is 7-day on and off in each subsequent 28-day cycles starting from Cycle 1. Based on serum phosphate (PO4) levels, there was an option to up-titrate erdafitinib dose to 12 mg, orally, once daily starting from Cycle 2 Day 1 until disease progression, unacceptable toxicity, or any other reason for treatment discontinuation.	Main Study: Regimen 3: Erdafitinib 8 mg/ 9 mg Participants received single dose of erdafitinib 8 mg tablet, orally, once daily, starting from Day 1 through Day 28 in each subsequent 28-day cycles starting from Cycle 1. Based on serum PO4 levels, there was an option to up-titrate erdafitinib dose to 9 mg, orally, once daily starting from Cycle 1 Day 15 until disease progression, unacceptable toxicity, or any other reason for treatment discontinuation.
Drug-Drug Interaction (DDI) Substudy: Time to Reach the Maximum Observed Plasma Concentration (Tmax) of 1-OH-Midazolam (Midazolam Metabolite) Alone or in Combination With Erdafitinib	0.58 Hours Interval 0.45 to 4.0	0.58 Hours Interval 0.47 to 2.08	—

PRIMARY outcome

Timeframe: Cycle 1 Day -1 (predose) up to Day 14 post dose (each cycle length=28 days)

Tmax is the time to reach maximum observed plasma concentration of metformin alone or in combination with erdafitinib

Outcome measures

Outcome measures
Measure	DDI Study: Metformin 1000 mg + Erdafitinib 8 mg n=19 Participants Participants received single dose of metformin 1000 mg tablet, orally, once daily, starting from Day -1 through Day 14 of Cycle 1 along with erdafitinib 8 mg starting from Day 1 up to Day 15 of Cycle 1 (each cycle length=28 days).	Main Study: Regimen 1: Erdafitinib 10 Milligrams (mg)/ 12 mg n=20 Participants Participants received single dose of erdafitinib 10 mg tablet, orally, once daily, starting from Day 1 through Day 7 and from Day 15 through Day 21 and so on, that is 7-day on and off in each subsequent 28-day cycles starting from Cycle 1. Based on serum phosphate (PO4) levels, there was an option to up-titrate erdafitinib dose to 12 mg, orally, once daily starting from Cycle 2 Day 1 until disease progression, unacceptable toxicity, or any other reason for treatment discontinuation.	Main Study: Regimen 3: Erdafitinib 8 mg/ 9 mg Participants received single dose of erdafitinib 8 mg tablet, orally, once daily, starting from Day 1 through Day 28 in each subsequent 28-day cycles starting from Cycle 1. Based on serum PO4 levels, there was an option to up-titrate erdafitinib dose to 9 mg, orally, once daily starting from Cycle 1 Day 15 until disease progression, unacceptable toxicity, or any other reason for treatment discontinuation.
Drug-Drug Interaction (DDI) Substudy: Time to Reach the Maximum Observed Plasma Concentration (Tmax) of Metformin Alone or in Combination With Erdafitinib	3.00 Hours Interval 0.5 to 8.08	2.04 Hours Interval 0.42 to 5.0	—

PRIMARY outcome

Timeframe: Cycle 1 Day -2 (predose) up to Day 13 post dose (each cycle length=28 days)

AUC(0-last) is the area under the plasma concentration versus time curve from time 0 to the time of the last measurable concentration of midazolam alone or in combination with erdafitinib.

Outcome measures

Outcome measures
Measure	DDI Study: Metformin 1000 mg + Erdafitinib 8 mg n=22 Participants Participants received single dose of metformin 1000 mg tablet, orally, once daily, starting from Day -1 through Day 14 of Cycle 1 along with erdafitinib 8 mg starting from Day 1 up to Day 15 of Cycle 1 (each cycle length=28 days).	Main Study: Regimen 1: Erdafitinib 10 Milligrams (mg)/ 12 mg n=23 Participants Participants received single dose of erdafitinib 10 mg tablet, orally, once daily, starting from Day 1 through Day 7 and from Day 15 through Day 21 and so on, that is 7-day on and off in each subsequent 28-day cycles starting from Cycle 1. Based on serum phosphate (PO4) levels, there was an option to up-titrate erdafitinib dose to 12 mg, orally, once daily starting from Cycle 2 Day 1 until disease progression, unacceptable toxicity, or any other reason for treatment discontinuation.	Main Study: Regimen 3: Erdafitinib 8 mg/ 9 mg Participants received single dose of erdafitinib 8 mg tablet, orally, once daily, starting from Day 1 through Day 28 in each subsequent 28-day cycles starting from Cycle 1. Based on serum PO4 levels, there was an option to up-titrate erdafitinib dose to 9 mg, orally, once daily starting from Cycle 1 Day 15 until disease progression, unacceptable toxicity, or any other reason for treatment discontinuation.
Drug-Drug Interaction (DDI) Substudy: Area Under the Plasma Concentration Versus Time Curve From Time 0 to the Time of the Last Measurable Concentration (AUC[0-last]) of Midazolam Alone or in Combination With Erdafitinib	57.1 Nanograms hours per milliliter (ng*h/mL) Standard Deviation 27.2	64.4 Nanograms hours per milliliter (ng*h/mL) Standard Deviation 26.8	—

PRIMARY outcome

Timeframe: Cycle 1 Day -2 (predose) up to Day 13 post dose (each cycle length=28 days)

AUC(0-last) is the area under the plasma concentration versus time curve from time 0 to the time of the last measurable concentration of 1-OH-Midazolam alone or in combination with erdafitinib.

Outcome measures

Outcome measures
Measure	DDI Study: Metformin 1000 mg + Erdafitinib 8 mg n=22 Participants Participants received single dose of metformin 1000 mg tablet, orally, once daily, starting from Day -1 through Day 14 of Cycle 1 along with erdafitinib 8 mg starting from Day 1 up to Day 15 of Cycle 1 (each cycle length=28 days).	Main Study: Regimen 1: Erdafitinib 10 Milligrams (mg)/ 12 mg n=23 Participants Participants received single dose of erdafitinib 10 mg tablet, orally, once daily, starting from Day 1 through Day 7 and from Day 15 through Day 21 and so on, that is 7-day on and off in each subsequent 28-day cycles starting from Cycle 1. Based on serum phosphate (PO4) levels, there was an option to up-titrate erdafitinib dose to 12 mg, orally, once daily starting from Cycle 2 Day 1 until disease progression, unacceptable toxicity, or any other reason for treatment discontinuation.	Main Study: Regimen 3: Erdafitinib 8 mg/ 9 mg Participants received single dose of erdafitinib 8 mg tablet, orally, once daily, starting from Day 1 through Day 28 in each subsequent 28-day cycles starting from Cycle 1. Based on serum PO4 levels, there was an option to up-titrate erdafitinib dose to 9 mg, orally, once daily starting from Cycle 1 Day 15 until disease progression, unacceptable toxicity, or any other reason for treatment discontinuation.
Drug-Drug Interaction (DDI) Substudy: Area Under the Plasma Concentration Versus Time Curve From Time 0 to the Time of the Last Measurable Concentration (AUC[0-last]) of 1-OH-Midazolam (Midazolam Metabolite) Alone or in Combination With Erdafitinib	15.1 ng*h/mL Standard Deviation 10.4	15.8 ng*h/mL Standard Deviation 9.59	—

PRIMARY outcome

Timeframe: Cycle 1 Day -1 (predose) up to Day 14 post dose (each cycle length=28 days)

AUC(0-last) is the area under the plasma concentration versus time curve from time 0 to the time of the last measurable concentration of metformin alone or in combination with erdafitinib.

Outcome measures

Outcome measures
Measure	DDI Study: Metformin 1000 mg + Erdafitinib 8 mg n=19 Participants Participants received single dose of metformin 1000 mg tablet, orally, once daily, starting from Day -1 through Day 14 of Cycle 1 along with erdafitinib 8 mg starting from Day 1 up to Day 15 of Cycle 1 (each cycle length=28 days).	Main Study: Regimen 1: Erdafitinib 10 Milligrams (mg)/ 12 mg n=20 Participants Participants received single dose of erdafitinib 10 mg tablet, orally, once daily, starting from Day 1 through Day 7 and from Day 15 through Day 21 and so on, that is 7-day on and off in each subsequent 28-day cycles starting from Cycle 1. Based on serum phosphate (PO4) levels, there was an option to up-titrate erdafitinib dose to 12 mg, orally, once daily starting from Cycle 2 Day 1 until disease progression, unacceptable toxicity, or any other reason for treatment discontinuation.	Main Study: Regimen 3: Erdafitinib 8 mg/ 9 mg Participants received single dose of erdafitinib 8 mg tablet, orally, once daily, starting from Day 1 through Day 28 in each subsequent 28-day cycles starting from Cycle 1. Based on serum PO4 levels, there was an option to up-titrate erdafitinib dose to 9 mg, orally, once daily starting from Cycle 1 Day 15 until disease progression, unacceptable toxicity, or any other reason for treatment discontinuation.
Drug-Drug Interaction (DDI) Substudy: Area Under the Plasma Concentration Versus Time Curve From Time 0 to the Time of the Last Measurable Concentration (AUC[0-last]) of Metformin Alone or in Combination With Erdafitinib	26917 ng*h/mL Standard Deviation 17973	22015 ng*h/mL Standard Deviation 11967	—

PRIMARY outcome

Timeframe: Cycle 1 Day -2 (predose) up to Day 13 post dose (each cycle length=28 days)

AUC(0-Infinity) is the area under the plasma concentration versus time curve from time 0 to the infinite time of midazolam alone or in combination with erdafitinib.

Outcome measures

Outcome measures
Measure	DDI Study: Metformin 1000 mg + Erdafitinib 8 mg n=17 Participants Participants received single dose of metformin 1000 mg tablet, orally, once daily, starting from Day -1 through Day 14 of Cycle 1 along with erdafitinib 8 mg starting from Day 1 up to Day 15 of Cycle 1 (each cycle length=28 days).	Main Study: Regimen 1: Erdafitinib 10 Milligrams (mg)/ 12 mg n=20 Participants Participants received single dose of erdafitinib 10 mg tablet, orally, once daily, starting from Day 1 through Day 7 and from Day 15 through Day 21 and so on, that is 7-day on and off in each subsequent 28-day cycles starting from Cycle 1. Based on serum phosphate (PO4) levels, there was an option to up-titrate erdafitinib dose to 12 mg, orally, once daily starting from Cycle 2 Day 1 until disease progression, unacceptable toxicity, or any other reason for treatment discontinuation.	Main Study: Regimen 3: Erdafitinib 8 mg/ 9 mg Participants received single dose of erdafitinib 8 mg tablet, orally, once daily, starting from Day 1 through Day 28 in each subsequent 28-day cycles starting from Cycle 1. Based on serum PO4 levels, there was an option to up-titrate erdafitinib dose to 9 mg, orally, once daily starting from Cycle 1 Day 15 until disease progression, unacceptable toxicity, or any other reason for treatment discontinuation.
Drug-Drug Interaction (DDI) Substudy: Area Under the Plasma Concentration Versus Time Curve From Time 0 to the Infinite Time (AUC[0-Infinity]) of Midazolam Alone or in Combination With Erdafitinib	55.9 ng*h/mL Standard Deviation 28.2	69.8 ng*h/mL Standard Deviation 30.5	—

PRIMARY outcome

Timeframe: Cycle 1 Day -2 (predose) up to Day 13 post dose (each cycle length=28 days)

AUC(0-Infinity) is the area under the plasma concentration versus time curve from time 0 to the infinite time of 1-OH-Midazolam alone or in combination with erdafitinib.

Outcome measures

Outcome measures
Measure	DDI Study: Metformin 1000 mg + Erdafitinib 8 mg n=13 Participants Participants received single dose of metformin 1000 mg tablet, orally, once daily, starting from Day -1 through Day 14 of Cycle 1 along with erdafitinib 8 mg starting from Day 1 up to Day 15 of Cycle 1 (each cycle length=28 days).	Main Study: Regimen 1: Erdafitinib 10 Milligrams (mg)/ 12 mg n=18 Participants Participants received single dose of erdafitinib 10 mg tablet, orally, once daily, starting from Day 1 through Day 7 and from Day 15 through Day 21 and so on, that is 7-day on and off in each subsequent 28-day cycles starting from Cycle 1. Based on serum phosphate (PO4) levels, there was an option to up-titrate erdafitinib dose to 12 mg, orally, once daily starting from Cycle 2 Day 1 until disease progression, unacceptable toxicity, or any other reason for treatment discontinuation.	Main Study: Regimen 3: Erdafitinib 8 mg/ 9 mg Participants received single dose of erdafitinib 8 mg tablet, orally, once daily, starting from Day 1 through Day 28 in each subsequent 28-day cycles starting from Cycle 1. Based on serum PO4 levels, there was an option to up-titrate erdafitinib dose to 9 mg, orally, once daily starting from Cycle 1 Day 15 until disease progression, unacceptable toxicity, or any other reason for treatment discontinuation.
Drug-Drug Interaction (DDI) Substudy: Area Under the Plasma Concentration Versus Time Curve From Time 0 to the Infinite Time (AUC[0-Infinity]) of 1-OH-Midazolam (Midazolam Metabolite) Alone or in Combination With Erdafitinib	18.4 ng*h/mL Standard Deviation 13.2	18.1 ng*h/mL Standard Deviation 10.8	—

PRIMARY outcome

Timeframe: Cycle 1 Day -1 (predose) up to Day 14 post dose (each cycle length=28 days)

AUC(0-Infinity) is the area under the plasma concentration versus time curve from time 0 to the infinite time of metformin alone or in combination with erdafitinib

Outcome measures

Outcome measures
Measure	DDI Study: Metformin 1000 mg + Erdafitinib 8 mg n=17 Participants Participants received single dose of metformin 1000 mg tablet, orally, once daily, starting from Day -1 through Day 14 of Cycle 1 along with erdafitinib 8 mg starting from Day 1 up to Day 15 of Cycle 1 (each cycle length=28 days).	Main Study: Regimen 1: Erdafitinib 10 Milligrams (mg)/ 12 mg n=20 Participants Participants received single dose of erdafitinib 10 mg tablet, orally, once daily, starting from Day 1 through Day 7 and from Day 15 through Day 21 and so on, that is 7-day on and off in each subsequent 28-day cycles starting from Cycle 1. Based on serum phosphate (PO4) levels, there was an option to up-titrate erdafitinib dose to 12 mg, orally, once daily starting from Cycle 2 Day 1 until disease progression, unacceptable toxicity, or any other reason for treatment discontinuation.	Main Study: Regimen 3: Erdafitinib 8 mg/ 9 mg Participants received single dose of erdafitinib 8 mg tablet, orally, once daily, starting from Day 1 through Day 28 in each subsequent 28-day cycles starting from Cycle 1. Based on serum PO4 levels, there was an option to up-titrate erdafitinib dose to 9 mg, orally, once daily starting from Cycle 1 Day 15 until disease progression, unacceptable toxicity, or any other reason for treatment discontinuation.
Drug-Drug Interaction (DDI) Substudy: Area Under the Plasma Concentration Versus Time Curve From Time 0 to the Infinite Time (AUC[0-Infinity]) of Metformin Alone or in Combination With Erdafitinib	28853 ng*h/mL Standard Deviation 21738	22917 ng*h/mL Standard Deviation 12539	—

SECONDARY outcome

Timeframe: From screening up to 6 years 2 months

Population: The population included participants who received at least 1 dose of study drug.

Progression-free survival is defined as the duration from the date of the first dose of study drug until the date of first documented evidence of progressive disease (or relapse for participants who experience CR during the study) or death due to any cause, whichever occurs first, regardless of the use of subsequent anticancer therapy. 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 less than (\<) 10 millimeters (mm). PR was defined as at least a 30 percent (%) decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

Outcome measures

Outcome measures
Measure	DDI Study: Metformin 1000 mg + Erdafitinib 8 mg n=78 Participants Participants received single dose of metformin 1000 mg tablet, orally, once daily, starting from Day -1 through Day 14 of Cycle 1 along with erdafitinib 8 mg starting from Day 1 up to Day 15 of Cycle 1 (each cycle length=28 days).	Main Study: Regimen 1: Erdafitinib 10 Milligrams (mg)/ 12 mg n=33 Participants Participants received single dose of erdafitinib 10 mg tablet, orally, once daily, starting from Day 1 through Day 7 and from Day 15 through Day 21 and so on, that is 7-day on and off in each subsequent 28-day cycles starting from Cycle 1. Based on serum phosphate (PO4) levels, there was an option to up-titrate erdafitinib dose to 12 mg, orally, once daily starting from Cycle 2 Day 1 until disease progression, unacceptable toxicity, or any other reason for treatment discontinuation.	Main Study: Regimen 3: Erdafitinib 8 mg/ 9 mg n=101 Participants Participants received single dose of erdafitinib 8 mg tablet, orally, once daily, starting from Day 1 through Day 28 in each subsequent 28-day cycles starting from Cycle 1. Based on serum PO4 levels, there was an option to up-titrate erdafitinib dose to 9 mg, orally, once daily starting from Cycle 1 Day 15 until disease progression, unacceptable toxicity, or any other reason for treatment discontinuation.
Main Study: Progression-free Survival (PFS)	5.26 months Interval 0.4 to 57.9	4.80 months Interval 1.1 to 25.3	5.52 months Interval 0.0 to 51.5

SECONDARY outcome

Timeframe: From screening up to 6 years 2 months

Population: The population included participants who received at least 1 dose of study drug and who had CR or PR.

DOR is defined as the time (in months) from the date of first observation of response (PR or CR) to the date of the first observation of progression or date of death, whatever the cause based on the RECIST version 1.1. CR: disappearance of all target and non-target lesions. All pathological (whether target or non-target) must have a reduction in their short axis \<10 mm. PR: at least a 30% decrease in the SOD of target lesions, taking as reference the baseline sum diameters. PD was defined as at least 20% increase (including an absolute increase of at least 5 mm) in the SOD of target lesions, taking as reference the smallest sum and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions.

Outcome measures

Outcome measures
Measure	DDI Study: Metformin 1000 mg + Erdafitinib 8 mg n=27 Participants Participants received single dose of metformin 1000 mg tablet, orally, once daily, starting from Day -1 through Day 14 of Cycle 1 along with erdafitinib 8 mg starting from Day 1 up to Day 15 of Cycle 1 (each cycle length=28 days).	Main Study: Regimen 1: Erdafitinib 10 Milligrams (mg)/ 12 mg n=7 Participants Participants received single dose of erdafitinib 10 mg tablet, orally, once daily, starting from Day 1 through Day 7 and from Day 15 through Day 21 and so on, that is 7-day on and off in each subsequent 28-day cycles starting from Cycle 1. Based on serum phosphate (PO4) levels, there was an option to up-titrate erdafitinib dose to 12 mg, orally, once daily starting from Cycle 2 Day 1 until disease progression, unacceptable toxicity, or any other reason for treatment discontinuation.	Main Study: Regimen 3: Erdafitinib 8 mg/ 9 mg n=40 Participants Participants received single dose of erdafitinib 8 mg tablet, orally, once daily, starting from Day 1 through Day 28 in each subsequent 28-day cycles starting from Cycle 1. Based on serum PO4 levels, there was an option to up-titrate erdafitinib dose to 9 mg, orally, once daily starting from Cycle 1 Day 15 until disease progression, unacceptable toxicity, or any other reason for treatment discontinuation.
Main Study: Duration of Response (DoR)	4.90 months Interval 2.5 to 56.5	13.37 months Interval 4.2 to 19.4	5.98 months Interval 2.4 to 50.2

SECONDARY outcome

Timeframe: From screening up to 6 years 2 months

Population: The population included participants who received at least 1 dose of study drug.

Overall survival is defined as the time from the date of first dose of study drug to the date of the participant's death from any cause.

Outcome measures

Outcome measures
Measure	DDI Study: Metformin 1000 mg + Erdafitinib 8 mg n=78 Participants Participants received single dose of metformin 1000 mg tablet, orally, once daily, starting from Day -1 through Day 14 of Cycle 1 along with erdafitinib 8 mg starting from Day 1 up to Day 15 of Cycle 1 (each cycle length=28 days).	Main Study: Regimen 1: Erdafitinib 10 Milligrams (mg)/ 12 mg n=33 Participants Participants received single dose of erdafitinib 10 mg tablet, orally, once daily, starting from Day 1 through Day 7 and from Day 15 through Day 21 and so on, that is 7-day on and off in each subsequent 28-day cycles starting from Cycle 1. Based on serum phosphate (PO4) levels, there was an option to up-titrate erdafitinib dose to 12 mg, orally, once daily starting from Cycle 2 Day 1 until disease progression, unacceptable toxicity, or any other reason for treatment discontinuation.	Main Study: Regimen 3: Erdafitinib 8 mg/ 9 mg n=101 Participants Participants received single dose of erdafitinib 8 mg tablet, orally, once daily, starting from Day 1 through Day 28 in each subsequent 28-day cycles starting from Cycle 1. Based on serum PO4 levels, there was an option to up-titrate erdafitinib dose to 9 mg, orally, once daily starting from Cycle 1 Day 15 until disease progression, unacceptable toxicity, or any other reason for treatment discontinuation.
Main Study: Overall Survival	8.64 months Interval 0.4 to 60.1	7.46 months Interval 1.7 to 64.0	11.30 months Interval 0.7 to 56.9

SECONDARY outcome

Timeframe: From Day 1 up to 6 years 2 months

Population: The population included participants who received at least 1 dose of study drug.

Percentage of participants with TEAEs were reported. 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. TEAEs are those events that occurred from first dose date through 30 days after last dose date, or day before subsequent anticancer therapy, whichever occurs first.

Outcome measures

Outcome measures
Measure	DDI Study: Metformin 1000 mg + Erdafitinib 8 mg n=78 Participants Participants received single dose of metformin 1000 mg tablet, orally, once daily, starting from Day -1 through Day 14 of Cycle 1 along with erdafitinib 8 mg starting from Day 1 up to Day 15 of Cycle 1 (each cycle length=28 days).	Main Study: Regimen 1: Erdafitinib 10 Milligrams (mg)/ 12 mg n=33 Participants Participants received single dose of erdafitinib 10 mg tablet, orally, once daily, starting from Day 1 through Day 7 and from Day 15 through Day 21 and so on, that is 7-day on and off in each subsequent 28-day cycles starting from Cycle 1. Based on serum phosphate (PO4) levels, there was an option to up-titrate erdafitinib dose to 12 mg, orally, once daily starting from Cycle 2 Day 1 until disease progression, unacceptable toxicity, or any other reason for treatment discontinuation.	Main Study: Regimen 3: Erdafitinib 8 mg/ 9 mg n=101 Participants Participants received single dose of erdafitinib 8 mg tablet, orally, once daily, starting from Day 1 through Day 28 in each subsequent 28-day cycles starting from Cycle 1. Based on serum PO4 levels, there was an option to up-titrate erdafitinib dose to 9 mg, orally, once daily starting from Cycle 1 Day 15 until disease progression, unacceptable toxicity, or any other reason for treatment discontinuation.
Main Study: Percentage of Participants With Treatment-emergent Adverse Event (TEAEs)	100 Percentage of Participants	100 Percentage of Participants	100 Percentage of Participants

SECONDARY outcome

Timeframe: Cycle 1 Days 1 and 21: Pre-dose up to 2 hours post-dose (each cycle length=28 days)

Population: Pharmacokinetic analysis set included all participants who received at least 1 dose of study drug and had at least 1 sample collected during treatment to determine the drug concentration. Here, 'N' (number of participants analyzed) signifies participants evaluable for this outcome measure. Here, 'n' (number analyzed) signifies participants evaluable for this outcome measure at specified timepoints.

C2h is the plasma concentration of erdafitinib at 2 hours.

Outcome measures

Outcome measures
Measure	DDI Study: Metformin 1000 mg + Erdafitinib 8 mg n=74 Participants Participants received single dose of metformin 1000 mg tablet, orally, once daily, starting from Day -1 through Day 14 of Cycle 1 along with erdafitinib 8 mg starting from Day 1 up to Day 15 of Cycle 1 (each cycle length=28 days).	Main Study: Regimen 1: Erdafitinib 10 Milligrams (mg)/ 12 mg n=32 Participants Participants received single dose of erdafitinib 10 mg tablet, orally, once daily, starting from Day 1 through Day 7 and from Day 15 through Day 21 and so on, that is 7-day on and off in each subsequent 28-day cycles starting from Cycle 1. Based on serum phosphate (PO4) levels, there was an option to up-titrate erdafitinib dose to 12 mg, orally, once daily starting from Cycle 2 Day 1 until disease progression, unacceptable toxicity, or any other reason for treatment discontinuation.	Main Study: Regimen 3: Erdafitinib 8 mg/ 9 mg n=92 Participants Participants received single dose of erdafitinib 8 mg tablet, orally, once daily, starting from Day 1 through Day 28 in each subsequent 28-day cycles starting from Cycle 1. Based on serum PO4 levels, there was an option to up-titrate erdafitinib dose to 9 mg, orally, once daily starting from Cycle 1 Day 15 until disease progression, unacceptable toxicity, or any other reason for treatment discontinuation.
Main Study: Plasma Concentration of Erdafitinib at 2 Hours (C2h) Cycle 1 Day 21	1255.1 ng/mL Standard Deviation 640.0	1686.5 ng/mL Standard Deviation 872.3	1371.4 ng/mL Standard Deviation 586.6
Main Study: Plasma Concentration of Erdafitinib at 2 Hours (C2h) Cycle 1 Day 1	311.0 ng/mL Standard Deviation 134.8	529.5 ng/mL Standard Deviation 224.9	373.0 ng/mL Standard Deviation 168.1

SECONDARY outcome

Timeframe: Cycle 1 Days 1 and 21: Pre-dose up to 4 hours post-dose (each cycle length=28 days)

Population: Pharmacokinetic analysis set included all participants who received at least 1 dose of study drug and had at least 1 sample collected during treatment to determine the drug concentration. Here, 'N' (number of participants analyzed) signifies participants evaluable for this outcome measure. Here, 'n' (number analyzed) signifies participants evaluable for this outcome measure at specified timepoints.

C4h is the plasma concentration of erdafitinib at 4 hours.

Outcome measures

Outcome measures
Measure	DDI Study: Metformin 1000 mg + Erdafitinib 8 mg n=74 Participants Participants received single dose of metformin 1000 mg tablet, orally, once daily, starting from Day -1 through Day 14 of Cycle 1 along with erdafitinib 8 mg starting from Day 1 up to Day 15 of Cycle 1 (each cycle length=28 days).	Main Study: Regimen 1: Erdafitinib 10 Milligrams (mg)/ 12 mg n=32 Participants Participants received single dose of erdafitinib 10 mg tablet, orally, once daily, starting from Day 1 through Day 7 and from Day 15 through Day 21 and so on, that is 7-day on and off in each subsequent 28-day cycles starting from Cycle 1. Based on serum phosphate (PO4) levels, there was an option to up-titrate erdafitinib dose to 12 mg, orally, once daily starting from Cycle 2 Day 1 until disease progression, unacceptable toxicity, or any other reason for treatment discontinuation.	Main Study: Regimen 3: Erdafitinib 8 mg/ 9 mg n=91 Participants Participants received single dose of erdafitinib 8 mg tablet, orally, once daily, starting from Day 1 through Day 28 in each subsequent 28-day cycles starting from Cycle 1. Based on serum PO4 levels, there was an option to up-titrate erdafitinib dose to 9 mg, orally, once daily starting from Cycle 1 Day 15 until disease progression, unacceptable toxicity, or any other reason for treatment discontinuation.
Main Study: Plasma Concentration of Erdafitinib at 4 Hours (C4h) Cycle 1 Day 1	290.0 ng/mL Standard Deviation 117.9	504.0 ng/mL Standard Deviation 189.6	365.3 ng/mL Standard Deviation 155.6
Main Study: Plasma Concentration of Erdafitinib at 4 Hours (C4h) Cycle 1 Day 21	1257.4 ng/mL Standard Deviation 663.2	1753.4 ng/mL Standard Deviation 917.8	1329.9 ng/mL Standard Deviation 550.1

Adverse Events

Main Study: Regimen 1: Erdafitinib 10 Milligrams (mg)/ 12 mg

Serious events: 14 serious events

Other events: 32 other events

Deaths: 31 deaths

Main Study: Regimen 2: Erdafitinib 6 mg/ 8 mg

Serious events: 39 serious events

Other events: 78 other events

Deaths: 62 deaths

Main Study: Regimen 3: Erdafitinib 8 mg/ 9 mg

Serious events: 47 serious events

Other events: 101 other events

Deaths: 83 deaths

Drug-Drug Interaction (DDI) Sub-study: Midazolam 2.5 mg + Metformin 1000 mg + Erdafitinib 8/9 mg

Serious events: 9 serious events

Other events: 25 other events

Deaths: 3 deaths

Serious adverse events

Other adverse events

Additional Information

Executive Medical Director

Janssen Research & Development, LLC

Phone: 844-434-4210

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee If an investigator wishes to publish information from the study, a copy of the manuscript must be provided to the sponsor for review at least 60 days before submission for publication or presentation. If requested by the sponsor in writing, the investigator will withhold such publication for up to an additional 60 days to allow for filing of a patent application.
Publication restrictions are in place

Restriction type: OTHER