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

NCT02365597 | Active Not Recruiting Phase 2 Results DMC

• 4 other identifiers: CR10506542756493BLC20012014-002408-262023-510273-34-00
• Study Type: interventional
• Target: 239
• Locations: 15 countries
• Sites: 105

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.

Conditions

Urothelial Cancer

Keywords

Urothelial Cancer; JNJ-42756493; Erdafitinib; Tyrosine Kinase Inhibitor

Outcome Measures

Primary Outcomes (13)

• 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.

  From Cycle 1 Day 1 up to 6 years 2 months

• 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.

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

• 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.

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

• 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

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

• 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.

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

• 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.

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

• 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

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

• 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.

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

• 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.

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

• 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.

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

• 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.

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

• 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.

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

• 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

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

Secondary Outcomes (6)

• Main Study: Progression-free Survival (PFS)

  From screening up to 6 years 2 months

• Main Study: Duration of Response (DoR)

  From screening up to 6 years 2 months

• Main Study: Overall Survival

  From screening up to 6 years 2 months

• Main Study: Percentage of Participants With Treatment-emergent Adverse Event (TEAEs)

  From Day 1 up to 6 years 2 months

• 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)

Study Arms (1)

Erdafitinib (8 milligram)

EXPERIMENTAL

Prior to interim analysis 1 (IA1), there were 2 treatment regimens: Regimen 1 (10 milligram \[mg\] once daily, 7 days on/7 days off); and Regimen 2 (6 mg once daily for 28 days). Following IA1, Regimen 1 is closed for further enrollment and starting dose of Regimen 2 is increased to 8 mg once daily for 28 days on a 28-day cycle (referred to as Regimen 3). Participants who enrolled in DDI substudy will receive pretreatment with single doses of midazolam (Day -2) and metformin (Day -1). Participants enrolled in DDI substudy will receive 8 mg erdafitinib treatment from Day 1 to Day 15, single doses of midazolam 2.5 mg (Day 13) and metformin 1000 mg (Day 14) and erdafitinib treatment will continued until disease progression. Participants who completed the DDI substudy and continue to benefit from erdafitinib treatment, will continue to receive erdafitinib in long-term extension (LTE) phase.

Drug: Erdafitinib; Drug: Midazolam; Drug: Metformin

Interventions

Erdafitinib DRUG

8 mg orally once daily for 28 days on a 28 day cycle.

Also known as: JNJ-42756493

Erdafitinib (8 milligram)

Midazolam DRUG

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.

Erdafitinib (8 milligram)

Metformin DRUG

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.

Erdafitinib (8 milligram)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Janssen Research & Development, LLC: lead

Study Sites (105)

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Sedona, Arizona, United States

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Los Angeles, California, United States

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Orange, California, United States

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Sacramento, California, United States

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Stanford, California, United States

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Aurora, Colorado, United States

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Washington D.C., District of Columbia, United States

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Chicago, Illinois, United States

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Iowa City, Iowa, United States

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Louisville, Kentucky, United States

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Minneapolis, Minnesota, United States

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Omaha, Nebraska, United States

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Las Vegas, Nevada, United States

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New York, New York, United States

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Charlotte, North Carolina, United States

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Medford, Oregon, United States

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Tualatin, Oregon, United States

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Hershey, Pennsylvania, United States

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Pittsburgh, Pennsylvania, United States

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Myrtle Beach, South Carolina, United States

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Nashville, Tennessee, United States

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Dallas, Texas, United States

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Denton, Texas, United States

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Houston, Texas, United States

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Hampton, Virginia, United States

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Graz, Austria

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Linz, Austria

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Vienna, Austria

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Aalst, Belgium

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Brussels, Belgium

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Charleroi, Belgium

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Ghent, Belgium

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Wilrijk, Belgium

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Angers, France

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Bordeaux, France

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Caen Cédex 05, France

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Dijon, France

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Lyon, France

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Nice, France

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Nîmes, France

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Paris, France

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Saint-Herblain, France

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Suresnes, France

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Villejuif, France

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Berlin, Germany

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Erlangen, Germany

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Essen, Germany

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Freiburg im Breisgau, Germany

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Göttingen, Germany

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Greifswald, Germany

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Hamburg, Germany

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Hanover, Germany

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Heidelberg, Germany

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München, Germany

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Münster, Germany

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Regensburg, Germany

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Straubing, Germany

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Weiden/Opf, Germany

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Bangalore, India

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Kolkata, India

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Mira Road (East), India

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Nadiād, India

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Beer Yaakov, Israel

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Beersheba, Israel

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Haifa, Israel

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Kfar Saba, Israel

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Petah Tikva, Israel

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Tel Aviv, Israel

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Chisinau, Moldova

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Bucharest, Romania

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Cluj-Napoca, Romania

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Craiova, Romania

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Iași, Romania

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Barnaul, Russia

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Moscow, Russia

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Omsk, Russia

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Pyatigorsk, Russia

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Saint Petersburg, Russia

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Ufa, Russia

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Daejeon, South Korea

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Goyang-si, South Korea

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Incheon, South Korea

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Seoul, South Korea

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Badalona, Spain

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Barcelona, Spain

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Madrid, Spain

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Málaga, Spain

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Pamplona, Spain

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Sabadell, Spain

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Santander, Spain

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Santiago de Compostela, Spain

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Seville, Spain

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Valencia, Spain

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Taichung, Taiwan

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Tainan, Taiwan

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Taipei, Taiwan

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Taoyuan, Taiwan

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Istanbul, Turkey (Türkiye)

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Blackburn, United Kingdom

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Dundee, United Kingdom

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Essex, United Kingdom

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London, United Kingdom

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Metropolitan Borough of Wirral, United Kingdom

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Plymouth, United Kingdom

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Sutton, United Kingdom

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Related Publications (3)

• Siefker-Radtke AO, Necchi A, Park SH, Garcia-Donas J, Huddart RA, Burgess EF, Fleming MT, Rezazadeh Kalebasty A, Mellado B, Varlamov S, Joshi M, Duran I, Tagawa ST, Zakharia Y, Akapame S, Santiago-Walker AE, Monga M, O'Hagan A, Loriot Y; BLC2001 Study Group. Efficacy and safety of erdafitinib in patients with locally advanced or metastatic urothelial carcinoma: long-term follow-up of a phase 2 study. Lancet Oncol. 2022 Feb;23(2):248-258. doi: 10.1016/S1470-2045(21)00660-4. Epub 2022 Jan 11.

  PMID: 35030333 DERIVED

• Dosne AG, Valade E, Goeyvaerts N, De Porre P, Avadhani A, O'Hagan A, Li LY, Ouellet D, Perez Ruixo JJ. Exposure-response analyses of erdafitinib in patients with locally advanced or metastatic urothelial carcinoma. Cancer Chemother Pharmacol. 2022 Feb;89(2):151-164. doi: 10.1007/s00280-021-04381-4. Epub 2022 Jan 3.

  PMID: 34977972 DERIVED

• Loriot Y, Necchi A, Park SH, Garcia-Donas J, Huddart R, Burgess E, Fleming M, Rezazadeh A, Mellado B, Varlamov S, Joshi M, Duran I, Tagawa ST, Zakharia Y, Zhong B, Stuyckens K, Santiago-Walker A, De Porre P, O'Hagan A, Avadhani A, Siefker-Radtke AO; BLC2001 Study Group. Erdafitinib in Locally Advanced or Metastatic Urothelial Carcinoma. N Engl J Med. 2019 Jul 25;381(4):338-348. doi: 10.1056/NEJMoa1817323.

  PMID: 31340094 DERIVED

MeSH Terms

Interventions

erdafitinib; Midazolam; Metformin

Intervention Hierarchy (Ancestors)

Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Biguanides; Guanidines; Amidines; Organic Chemicals

Results Point of Contact

• Title: Executive Medical Director
• Organization: Janssen Research & Development, LLC

ClinicalTrialDisclosure@its.jnj.com

844-434-4210

Study Officials

• Janssen Research & Development, LLC Clinical Trial

  Janssen Research & Development, LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR
• Expanded Access: Yes

Study Record Dates

• First Submitted: January 29, 2015
• First Posted: February 19, 2015
• Study Start: April 22, 2015
• Primary Completion: September 15, 2022
• Study Completion (Estimated): March 31, 2027
• Last Updated: June 5, 2026
• Results First Posted: October 10, 2023

Record last verified: 2026-06

Locations

FR (11); TU (1); IL (6); GB (7); RO (4); ES (10); AU (3); RU (6); MO (1); IN (4); US (25); KR (4); BE (5); TW (4); DE (14)