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

PRIMARY OUTCOMES

Primary Outcome 1 - Measure: Main Study: Percentage of Participants With Best (Overall) Objective Response

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

Primary Outcome 2 - Measure: Drug-Drug Interaction (DDI) Substudy: Maximum Observed Plasma Concentration (Cmax) of Midazolam Alone or in Combination With Erdafitinib

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

Primary Outcome 3 - Measure: Drug-Drug Interaction (DDI) Substudy: Maximum Observed Plasma Concentration (Cmax) of 1-OH-Midazolam (Midazolam Metabolite) Alone or in Combination With Erdafitinib

Primary Outcome 3 - Timeframe: Cycle 1 Day -2 (predose) up to Day 13 post dose (each cycle length=28 days)

Primary Outcome 4 - Measure: Drug-Drug Interaction (DDI) Substudy: Maximum Observed Plasma Concentration (Cmax) of Metformin Alone or in Combination With Erdafitinib

Primary Outcome 4 - Timeframe: Cycle 1 Day -1 (predose) up to Day 14 post dose (each cycle length=28 days)

Primary Outcome 5 - Measure: Drug-Drug Interaction (DDI) Substudy: Time to Reach the Maximum Observed Plasma Concentration (Tmax) of Midazolam Alone or in Combination With Erdafitinib

Primary Outcome 5 - Timeframe: Cycle 1 Day -2 (predose) up to Day 13 post dose (each cycle length=28 days)

Primary Outcome 6 - Measure: 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

Primary Outcome 6 - Timeframe: Cycle 1 Day -2 (predose) up to Day 13 post dose (each cycle length=28 days)

Primary Outcome 7 - Measure: Drug-Drug Interaction (DDI) Substudy: Time to Reach the Maximum Observed Plasma Concentration (Tmax) of Metformin Alone or in Combination With Erdafitinib

Primary Outcome 7 - Timeframe: Cycle 1 Day -1 (predose) up to Day 14 post dose (each cycle length=28 days)

Primary Outcome 8 - Measure: 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

Primary Outcome 8 - Timeframe: Cycle 1 Day -2 (predose) up to Day 13 post dose (each cycle length=28 days)

Primary Outcome 9 - Measure: 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

Primary Outcome 9 - Timeframe: Cycle 1 Day -2 (predose) up to Day 13 post dose (each cycle length=28 days)

Primary Outcome 10 - Measure: 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

Primary Outcome 10 - Timeframe: Cycle 1 Day -1 (predose) up to Day 14 post dose (each cycle length=28 days)

Primary Outcome 11 - Measure: 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

Primary Outcome 11 - Timeframe: Cycle 1 Day -2 (predose) up to Day 13 post dose (each cycle length=28 days)

Primary Outcome 12 - Measure: 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

Primary Outcome 12 - Timeframe: Cycle 1 Day -2 (predose) up to Day 13 post dose (each cycle length=28 days)

Primary Outcome 13 - Measure: 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

Primary Outcome 13 - Timeframe: Cycle 1 Day -1 (predose) up to Day 14 post dose (each cycle length=28 days)

CONDITION

• Urothelial Cancer

ELIGIBILITY

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)

Gender: All

Minimum Age: 18 Years

Maximum Age: N/A

Healthy Volunteers: No

OFFICIAL INFORMATION

Name: Janssen Research & Development, LLC Clinical Trial

Role: Study Director

Affiliation: Janssen Research & Development, LLC

Overall Contact

Name: N/A

Phone: N/A

Email: N/A

LOCATION