Urothelial Cancer
Conditions
Keywords
Urothelial Cancer, JNJ-42756493, Erdafitinib, Tyrosine Kinase Inhibitor
Brief summary
The purpose of this study is to evaluate the objective response rate (complete response \[CR\]+ partial response \[PR\]) of the selected dose regimen in participants with metastatic or surgically unresectable urothelial cancers that harbor specific FGFR genomic alterations.
Detailed description
This is a multicenter, open-label study (participants will know the identity of study drugs administered) to evaluate the efficacy and safety of erdafitinib in participants with urothelial cancer. The study comprises a 30-days Screening Phase, a Treatment Phase comprised of 28-day treatment cycles that will continue until disease progression or unacceptable toxicity occurs in a long-term extension (LTE) phase, and a post-treatment Follow-up Phase that will extend from the End-of-Treatment Visit until the participant has died, withdraws consent, is lost to follow-up, or the end of the study, whichever comes first. The end of study is defined as the date when all participants have completed the study treatment (Regimens 1 to 3) and all participants enrolled under the drug-drug interaction (DDI) substudy are no longer receiving treatment with erdafitinib. The purpose of DDI sub-study is to evaluate the interaction of repeated doses of erdafitinib with a sensitive cytochrome 450 (CYP) 3A substrate (midazolam) and with an organic cation transporter 2 (OCT2) probe substrate (metformin). Safety will be monitored throughout the study.
Interventions
DRUGErdafitinib
8 mg orally once daily for 28 days on a 28 day cycle.
DRUGMidazolam
Participants who enrolled in DDI substudy will receive pretreatment with single dose of midazolam on Day -2 and single dose of midazolam on Day 13.
DRUGMetformin
Participants who enrolled in DDI substudy will receive pretreatment with single dose of metformin on Day -1 and single dose of metformin on Day 14.
Sponsors
Janssen Research & Development, LLC
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Must have histologic demonstration of metastatic or surgically unresectable urothelial cancer. Minor components of variant histology such as glandular or squamous differentiation, or evolution to more aggressive phenotypes such as sarcomatoid or micropapillary change are acceptable * Must have measurable disease according to the Response Evaluation Criteria in Solid Tumors (RECIST, version 1.1) at baseline * Must have an Eastern Cooperative Oncology Group (ECOG) performance status score 0, 1, or 2 * Must have adequate bone marrow, liver, and renal function as described in protocol * Negative pregnancy test (urine or serum beta human chorionic gonadotropin \[b-hCG\]) at Screening for women of child bearing potential who are sexually active * Must have shown disease progression according to RECIST, version 1.1, following prior chemotherapy for metastatic or surgically unresectable urothelial cancer. Participants who received neoadjuvant or adjuvant chemotherapy and showed disease recurrence or progression according to RECIST, version 1.1, within 12 months of the last dose are considered to have received chemotherapy in the metastatic setting. These participants will be referred to as chemo-refractory participants. (Participants who have shown disease progression according to RECIST, version 1.1 following prior treatment with anti-Programmed death-ligand 1 (anti PDL1/PD1) antibodies are also eligible) For DDI substudy * Disease progression following prior chemotherapy for metastatic or surgically unresectable urothelial cancer. Participants who received neoadjuvant or adjuvant chemotherapy and showed disease recurrence or progression within 12 months of the last dose are considered to have received chemotherapy in the metastatic setting
Exclusion criteria
* Received chemotherapy, targeted therapies, definitive radiotherapy, or treatment with an investigational anticancer agent within 2 weeks (in the case of nitrosoureas and mitomycin C, within 6 weeks; in the case of immunotherapy, within 4 weeks) before the first administration of study drug. Localized palliative radiation therapy (but should not include radiation to target lesions) and ongoing bisphosphonates and denosumab, are permitted * Has persistent phosphate level greater than upper limit of normal (ULN) during screening (within 14 days of treatment and prior to Cycle 1 Day 1) and despite medical management * Has a history of or current uncontrolled cardiovascular disease * Females who are pregnant, breast-feeding, or planning to become pregnant within 3 months after the last dose of study drug and males ho plan to father a child while enrolled in this study or within 5 months after the last dose of study drug * Has not recovered from reversible toxicity of prior anticancer therapy (except toxicities which are not clinically significant such as alopecia, skin discoloration, or Grade 1 neuropathy)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Drug-Drug Interaction (DDI) Substudy: Time to Reach the Maximum Observed Plasma Concentration (Tmax) of Metformin Alone or in Combination With Erdafitinib | 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 |
| Main Study: Percentage of Participants With Best (Overall) Objective Response | From Cycle 1 Day 1 up to 6 years 2 months | 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. |
| Drug-Drug Interaction (DDI) Substudy: Maximum Observed Plasma Concentration (Cmax) of Midazolam Alone or in Combination With Erdafitinib | Cycle 1 Day -2 (predose) up to Day 13 post dose | Cmax is the maximum observed plasma concentration of midazolam alone or in combination with erdafitinib. |
| Drug-Drug Interaction (DDI) Substudy: Maximum Observed Plasma Concentration (Cmax) of 1-OH-Midazolam (Midazolam Metabolite) Alone or in Combination With Erdafitinib | 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. |
| Drug-Drug Interaction (DDI) Substudy: Maximum Observed Plasma Concentration (Cmax) of Metformin Alone or in Combination With Erdafitinib | 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 |
| Drug-Drug Interaction (DDI) Substudy: Time to Reach the Maximum Observed Plasma Concentration (Tmax) of Midazolam Alone or in Combination With Erdafitinib | 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. |
| 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 | 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. |
| 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 | 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. |
| 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 | 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. |
| 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 | 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. |
| 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 | 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. |
| 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 | 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. |
| 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 | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Main Study: Progression-free Survival (PFS) | From screening up to 6 years 2 months | 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. |
| Main Study: Duration of Response (DoR) | From screening up to 6 years 2 months | 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. |
| Main Study: Overall Survival | From screening up to 6 years 2 months | 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. |
| Main Study: Percentage of Participants With Treatment-emergent Adverse Event (TEAEs) | From Day 1 up to 6 years 2 months | 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. |
| Main Study: Plasma Concentration of Erdafitinib at 2 Hours (C2h) | Cycle 1 Days 1 and 21: Pre-dose up to 2 hours post-dose (each cycle length=28 days) | C2h is the plasma concentration of erdafitinib at 2 hours. |
| Main Study: Plasma Concentration of Erdafitinib at 4 Hours (C4h) | Cycle 1 Days 1 and 21: Pre-dose up to 4 hours post-dose (each cycle length=28 days) | C4h is the plasma concentration of erdafitinib at 4 hours. |
Countries
Austria, Belgium, France, Germany, India, Israel, Moldova, Romania, Russia, South Korea, Spain, Taiwan, Turkey (Türkiye), United Kingdom, United States
Contacts
STUDY_DIRECTORJanssen Research & Development, LLC Clinical Trial
Janssen Research & Development, LLC
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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. | 33 |
| 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. | 78 |
| 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. | 101 |
| 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. | 25 |
| Total | 237 |
Baseline characteristics
| Characteristic | Main Study: Regimen 1: Erdafitinib 10 Milligrams (mg)/ 12 mg | Main Study: Regimen 2: Erdafitinib 6 mg/ 8 mg | Main Study: Regimen 3: Erdafitinib 8 mg/ 9 mg | Drug-Drug Interaction (DDI) Sub-study: Midazolam 2.5 mg + Metformin 1000 mg + Erdafitinib 8/9 mg | Total |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 22 Participants | 39 Participants | 62 Participants | 14 Participants | 137 Participants |
| Age, Categorical Between 18 and 65 years | 11 Participants | 39 Participants | 39 Participants | 11 Participants | 100 Participants |
| Age, Continuous | 68.6 years STANDARD_DEVIATION 7.98 | 64.5 years STANDARD_DEVIATION 10.36 | 66.1 years STANDARD_DEVIATION 10.2 | 64.8 years STANDARD_DEVIATION 10.35 | 65.8 years STANDARD_DEVIATION 10.03 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 2 Participants | 2 Participants | 1 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 25 Participants | 68 Participants | 75 Participants | 22 Participants | 190 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 7 Participants | 8 Participants | 24 Participants | 2 Participants | 41 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian | 2 Participants | 11 Participants | 5 Participants | 0 Participants | 18 Participants |
| Race/Ethnicity, Customized Black or African American | 0 Participants | 2 Participants | 2 Participants | 0 Participants | 4 Participants |
| Race/Ethnicity, Customized More than one race | 0 Participants | 0 Participants | 0 Participants | 3 Participants | 3 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Other | 0 Participants | 2 Participants | 1 Participants | 0 Participants | 3 Participants |
| Race/Ethnicity, Customized Unknown or Not Reported | 7 Participants | 7 Participants | 18 Participants | 2 Participants | 34 Participants |
| Race/Ethnicity, Customized White | 24 Participants | 56 Participants | 75 Participants | 20 Participants | 175 Participants |
| Region of Enrollment AUSTRIA | 0 Participants | 2 Participants | 2 Participants | 0 Participants | 4 Participants |
| Region of Enrollment BELGIUM | 3 Participants | 2 Participants | 4 Participants | 0 Participants | 9 Participants |
| Region of Enrollment FRANCE | 7 Participants | 9 Participants | 20 Participants | 1 Participants | 37 Participants |
| Region of Enrollment GERMANY | 0 Participants | 5 Participants | 6 Participants | 0 Participants | 11 Participants |
| Region of Enrollment INDIA | 0 Participants | 0 Participants | 0 Participants | 3 Participants | 3 Participants |
| Region of Enrollment ISRAEL | 0 Participants | 2 Participants | 3 Participants | 0 Participants | 5 Participants |
| Region of Enrollment ITALY | 4 Participants | 12 Participants | 19 Participants | 0 Participants | 35 Participants |
| Region of Enrollment MOLDOVA, REPUBLIC OF | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Region of Enrollment ROMANIA | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 2 Participants |
| Region of Enrollment RUSSIAN FEDERATION | 1 Participants | 7 Participants | 11 Participants | 0 Participants | 19 Participants |
| Region of Enrollment SOUTH KOREA | 2 Participants | 9 Participants | 3 Participants | 0 Participants | 14 Participants |
| Region of Enrollment SPAIN | 7 Participants | 8 Participants | 4 Participants | 20 Participants | 39 Participants |
| Region of Enrollment TAIWAN | 0 Participants | 2 Participants | 2 Participants | 0 Participants | 4 Participants |
| Region of Enrollment TURKEY | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Region of Enrollment UNITED KINGDOM | 1 Participants | 5 Participants | 5 Participants | 0 Participants | 11 Participants |
| Region of Enrollment UNITED STATES | 8 Participants | 13 Participants | 21 Participants | 0 Participants | 42 Participants |
| Sex: Female, Male Female | 11 Participants | 24 Participants | 24 Participants | 10 Participants | 69 Participants |
| Sex: Female, Male Male | 22 Participants | 54 Participants | 77 Participants | 15 Participants | 168 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 31 / 33 | 62 / 78 | 83 / 101 | 3 / 25 |
| other Total, other adverse events | 32 / 33 | 78 / 78 | 101 / 101 | 25 / 25 |
| serious Total, serious adverse events | 14 / 33 | 39 / 78 | 47 / 101 | 9 / 25 |
Outcome results
Primary
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
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.
Time frame: Cycle 1 Day -2 (predose) up to Day 13 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 number of participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Main Study: Regimen 1: Erdafitinib 10 Milligrams (mg)/ 12 mg | 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 | 18.1 ng*h/mL | Standard Deviation 10.8 |
| Main Study: Regimen 2: Erdafitinib 6 mg/ 8 mg | 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 |
Primary
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
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
Time frame: Cycle 1 Day -1 (predose) up to Day 14 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 number of participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Main Study: Regimen 1: Erdafitinib 10 Milligrams (mg)/ 12 mg | 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 | 22917 ng*h/mL | Standard Deviation 12539 |
| Main Study: Regimen 2: Erdafitinib 6 mg/ 8 mg | 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 |
Primary
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
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.
Time frame: Cycle 1 Day -2 (predose) up to Day 13 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 number of participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Main Study: Regimen 1: Erdafitinib 10 Milligrams (mg)/ 12 mg | 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 | 69.8 ng*h/mL | Standard Deviation 30.5 |
| Main Study: Regimen 2: Erdafitinib 6 mg/ 8 mg | 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 |
Primary
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
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.
Time frame: Cycle 1 Day -2 (predose) up to Day 13 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 number of participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Main Study: Regimen 1: Erdafitinib 10 Milligrams (mg)/ 12 mg | 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 | 15.8 ng*h/mL | Standard Deviation 9.59 |
| Main Study: Regimen 2: Erdafitinib 6 mg/ 8 mg | 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 |
Primary
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
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.
Time frame: Cycle 1 Day -1 (predose) up to Day 14 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 number of participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Main Study: Regimen 1: Erdafitinib 10 Milligrams (mg)/ 12 mg | 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 | 22015 ng*h/mL | Standard Deviation 11967 |
| Main Study: Regimen 2: Erdafitinib 6 mg/ 8 mg | 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 |
Primary
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
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.
Time frame: Cycle 1 Day -2 (predose) up to Day 13 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 number of participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Main Study: Regimen 1: Erdafitinib 10 Milligrams (mg)/ 12 mg | 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 | 64.4 Nanograms hours per milliliter (ng*h/mL) | Standard Deviation 26.8 |
| Main Study: Regimen 2: Erdafitinib 6 mg/ 8 mg | 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 |
Primary
Drug-Drug Interaction (DDI) Substudy: Maximum Observed Plasma Concentration (Cmax) of 1-OH-Midazolam (Midazolam Metabolite) Alone or in Combination With Erdafitinib
Cmax is the maximum observed plasma concentration of 1-OH-Midazolam (midazolam metabolite) alone or in combination with erdafitinib.
Time frame: Cycle 1 Day -2 (predose) up to Day 13 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 number of participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Main Study: Regimen 1: Erdafitinib 10 Milligrams (mg)/ 12 mg | Drug-Drug Interaction (DDI) Substudy: Maximum Observed Plasma Concentration (Cmax) of 1-OH-Midazolam (Midazolam Metabolite) Alone or in Combination With Erdafitinib | 5.39 ng/mL | Standard Deviation 3.42 |
| Main Study: Regimen 2: Erdafitinib 6 mg/ 8 mg | 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 2.6 |
Primary
Drug-Drug Interaction (DDI) Substudy: Maximum Observed Plasma Concentration (Cmax) of Metformin Alone or in Combination With Erdafitinib
Cmax is the maximum observed plasma concentration of metformin alone or in combination with erdafitinib
Time frame: Cycle 1 Day -1 (predose) up to Day 14 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 number of participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Main Study: Regimen 1: Erdafitinib 10 Milligrams (mg)/ 12 mg | Drug-Drug Interaction (DDI) Substudy: Maximum Observed Plasma Concentration (Cmax) of Metformin Alone or in Combination With Erdafitinib | 2465 ng/mL | Standard Deviation 986 |
| Main Study: Regimen 2: Erdafitinib 6 mg/ 8 mg | Drug-Drug Interaction (DDI) Substudy: Maximum Observed Plasma Concentration (Cmax) of Metformin Alone or in Combination With Erdafitinib | 2687 ng/mL | Standard Deviation 1127 |
Primary
Drug-Drug Interaction (DDI) Substudy: Maximum Observed Plasma Concentration (Cmax) of Midazolam Alone or in Combination With Erdafitinib
Cmax is the maximum observed plasma concentration of midazolam alone or in combination with erdafitinib.
Time frame: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Main Study: Regimen 1: Erdafitinib 10 Milligrams (mg)/ 12 mg | Drug-Drug Interaction (DDI) Substudy: Maximum Observed Plasma Concentration (Cmax) of Midazolam Alone or in Combination With Erdafitinib | 18.4 nanograms per milliliter (ng/mL) | Standard Deviation 7.32 |
| Main Study: Regimen 2: Erdafitinib 6 mg/ 8 mg | 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 5.9 |
Primary
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
Tmax is the time to reach the maximum observed plasma concentration of 1-OH-Midazolam alone or in combination with erdafitinib.
Time frame: Cycle 1 Day -2 (predose) up to Day 13 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 number of participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Main Study: Regimen 1: Erdafitinib 10 Milligrams (mg)/ 12 mg | 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 |
| Main Study: Regimen 2: Erdafitinib 6 mg/ 8 mg | 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 |
Primary
Drug-Drug Interaction (DDI) Substudy: Time to Reach the Maximum Observed Plasma Concentration (Tmax) of Metformin Alone or in Combination With Erdafitinib
Tmax is the time to reach maximum observed plasma concentration of metformin alone or in combination with erdafitinib
Time frame: Cycle 1 Day -1 (predose) up to Day 14 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 number of participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Main Study: Regimen 1: Erdafitinib 10 Milligrams (mg)/ 12 mg | Drug-Drug Interaction (DDI) Substudy: Time to Reach the Maximum Observed Plasma Concentration (Tmax) of Metformin Alone or in Combination With Erdafitinib | 2.04 Hours |
| Main Study: Regimen 2: Erdafitinib 6 mg/ 8 mg | 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 |
Primary
Drug-Drug Interaction (DDI) Substudy: Time to Reach the Maximum Observed Plasma Concentration (Tmax) of Midazolam Alone or in Combination With Erdafitinib
Tmax is the time to reach the maximum observed plasma concentration of midazolam alone or in combination with erdafitinib.
Time frame: Cycle 1 Day -2 (predose) up to Day 13 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 number of participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Main Study: Regimen 1: Erdafitinib 10 Milligrams (mg)/ 12 mg | Drug-Drug Interaction (DDI) Substudy: Time to Reach the Maximum Observed Plasma Concentration (Tmax) of Midazolam Alone or in Combination With Erdafitinib | 0.50 Hours |
| Main Study: Regimen 2: Erdafitinib 6 mg/ 8 mg | 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 |
Primary
Main Study: Percentage of Participants With Best (Overall) Objective Response
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.
Time frame: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Main Study: Regimen 1: Erdafitinib 10 Milligrams (mg)/ 12 mg | Main Study: Percentage of Participants With Best (Overall) Objective Response | 21.2 Percentage of Participants |
| Main Study: Regimen 2: Erdafitinib 6 mg/ 8 mg | Main Study: Percentage of Participants With Best (Overall) Objective Response | 34.6 Percentage of Participants |
| Main Study: Regimen 3: Erdafitinib 8 mg/ 9 mg | Main Study: Percentage of Participants With Best (Overall) Objective Response | 39.6 Percentage of Participants |
Secondary
Main Study: Duration of Response (DoR)
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.
Time frame: 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Main Study: Regimen 1: Erdafitinib 10 Milligrams (mg)/ 12 mg | Main Study: Duration of Response (DoR) | 13.37 months |
| Main Study: Regimen 2: Erdafitinib 6 mg/ 8 mg | Main Study: Duration of Response (DoR) | 4.90 months |
| Main Study: Regimen 3: Erdafitinib 8 mg/ 9 mg | Main Study: Duration of Response (DoR) | 5.98 months |
Secondary
Main Study: Overall Survival
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.
Time frame: From screening up to 6 years 2 months
Population: The population included participants who received at least 1 dose of study drug.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Main Study: Regimen 1: Erdafitinib 10 Milligrams (mg)/ 12 mg | Main Study: Overall Survival | 7.46 months |
| Main Study: Regimen 2: Erdafitinib 6 mg/ 8 mg | Main Study: Overall Survival | 8.64 months |
| Main Study: Regimen 3: Erdafitinib 8 mg/ 9 mg | Main Study: Overall Survival | 11.30 months |
Secondary
Main Study: Percentage of Participants With Treatment-emergent Adverse Event (TEAEs)
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.
Time frame: From Day 1 up to 6 years 2 months
Population: The population included participants who received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Main Study: Regimen 1: Erdafitinib 10 Milligrams (mg)/ 12 mg | Main Study: Percentage of Participants With Treatment-emergent Adverse Event (TEAEs) | 100 Percentage of Participants |
| Main Study: Regimen 2: Erdafitinib 6 mg/ 8 mg | Main Study: Percentage of Participants With Treatment-emergent Adverse Event (TEAEs) | 100 Percentage of Participants |
| Main Study: Regimen 3: Erdafitinib 8 mg/ 9 mg | Main Study: Percentage of Participants With Treatment-emergent Adverse Event (TEAEs) | 100 Percentage of Participants |
Secondary
Main Study: Plasma Concentration of Erdafitinib at 2 Hours (C2h)
C2h is the plasma concentration of erdafitinib at 2 hours.
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Main Study: Regimen 1: Erdafitinib 10 Milligrams (mg)/ 12 mg | Main Study: Plasma Concentration of Erdafitinib at 2 Hours (C2h) | Cycle 1 Day 1 | 529.5 ng/mL | Standard Deviation 224.9 |
| Main Study: Regimen 1: Erdafitinib 10 Milligrams (mg)/ 12 mg | Main Study: Plasma Concentration of Erdafitinib at 2 Hours (C2h) | Cycle 1 Day 21 | 1686.5 ng/mL | Standard Deviation 872.3 |
| Main Study: Regimen 2: Erdafitinib 6 mg/ 8 mg | Main Study: Plasma Concentration of Erdafitinib at 2 Hours (C2h) | Cycle 1 Day 1 | 311.0 ng/mL | Standard Deviation 134.8 |
| Main Study: Regimen 2: Erdafitinib 6 mg/ 8 mg | Main Study: Plasma Concentration of Erdafitinib at 2 Hours (C2h) | Cycle 1 Day 21 | 1255.1 ng/mL | Standard Deviation 640 |
| Main Study: Regimen 3: Erdafitinib 8 mg/ 9 mg | Main Study: Plasma Concentration of Erdafitinib at 2 Hours (C2h) | Cycle 1 Day 1 | 373.0 ng/mL | Standard Deviation 168.1 |
| Main Study: Regimen 3: Erdafitinib 8 mg/ 9 mg | Main Study: Plasma Concentration of Erdafitinib at 2 Hours (C2h) | Cycle 1 Day 21 | 1371.4 ng/mL | Standard Deviation 586.6 |
Secondary
Main Study: Plasma Concentration of Erdafitinib at 4 Hours (C4h)
C4h is the plasma concentration of erdafitinib at 4 hours.
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Main Study: Regimen 1: Erdafitinib 10 Milligrams (mg)/ 12 mg | Main Study: Plasma Concentration of Erdafitinib at 4 Hours (C4h) | Cycle 1 Day 21 | 1753.4 ng/mL | Standard Deviation 917.8 |
| Main Study: Regimen 1: Erdafitinib 10 Milligrams (mg)/ 12 mg | Main Study: Plasma Concentration of Erdafitinib at 4 Hours (C4h) | Cycle 1 Day 1 | 504.0 ng/mL | Standard Deviation 189.6 |
| Main Study: Regimen 2: Erdafitinib 6 mg/ 8 mg | Main Study: Plasma Concentration of Erdafitinib at 4 Hours (C4h) | Cycle 1 Day 21 | 1257.4 ng/mL | Standard Deviation 663.2 |
| Main Study: Regimen 2: Erdafitinib 6 mg/ 8 mg | Main Study: Plasma Concentration of Erdafitinib at 4 Hours (C4h) | Cycle 1 Day 1 | 290.0 ng/mL | Standard Deviation 117.9 |
| Main Study: Regimen 3: Erdafitinib 8 mg/ 9 mg | Main Study: Plasma Concentration of Erdafitinib at 4 Hours (C4h) | Cycle 1 Day 1 | 365.3 ng/mL | Standard Deviation 155.6 |
| Main Study: Regimen 3: Erdafitinib 8 mg/ 9 mg | Main Study: Plasma Concentration of Erdafitinib at 4 Hours (C4h) | Cycle 1 Day 21 | 1329.9 ng/mL | Standard Deviation 550.1 |
Secondary
Main Study: Progression-free Survival (PFS)
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.
Time frame: From screening up to 6 years 2 months
Population: The population included participants who received at least 1 dose of study drug.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Main Study: Regimen 1: Erdafitinib 10 Milligrams (mg)/ 12 mg | Main Study: Progression-free Survival (PFS) | 4.80 months |
| Main Study: Regimen 2: Erdafitinib 6 mg/ 8 mg | Main Study: Progression-free Survival (PFS) | 5.26 months |
| Main Study: Regimen 3: Erdafitinib 8 mg/ 9 mg | Main Study: Progression-free Survival (PFS) | 5.52 months |