A Study of Erdafitinib in Participants With Metastatic or Locally Advanced Urothelial Cancer

• ClinicalTrials.gov Identifier: NCT03473743
• Recruitment Status: Active, not recruiting
• First Posted: March 22, 2018
• Results First Posted: October 25, 2023
• Last Update Posted: April 25, 2024
• Sponsor: Janssen Research & Development, LLC
• Information provided by (Responsible Party): Janssen Research & Development, LLC

Tracking Information

• First Submitted Date: March 14, 2018
• First Posted Date: March 22, 2018
• Results First Submitted Date: September 29, 2023
• Results First Posted Date: October 25, 2023
• Last Update Posted Date: April 25, 2024
• Actual Study Start Date: April 5, 2018
• Actual Primary Completion Date: September 30, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: September 29, 2023)

• Phase 1b: Number of Participants With Dose-Limiting Toxicity (DLTs) [ Time Frame: Up to 8 weeks ]
  Number of participants with DLTs were reported. The DLTs as per National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI-CTCAE version 5.0) are specific adverse events defined as grade 3 (severe), grade 4 (life-threatening), and grade 5 (death) non-hematological toxicity or hematological toxicity.
• Phase 2: Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 by Investigator Assessment [ Time Frame: From Day 1 up to 36 months ]
  ORR is defined as the percentage of participants who achieved confirmed complete response (CR) or confirmed partial response (PR), according to response evaluation criteria in solid tumors (RECIST) version1.1. As per RECIST version 1.1, CR: disappearance of all lesions; all lymph nodes were non-pathological in size and normalization of tumor marker level; PR: greater than or equal to (>=) 30 percent (%) decrease in the sum of the diameters of all target lesions compared with baseline, in absence of new lesions or unequivocal progression of nontarget lesions.
• Phase 2: Number of Participants With Treatment-emergent Adverse Event (TEAEs) [ Time Frame: From Day 1 up to 36 months ]
  Number of participants with TEAEs were reported. An adverse event is any untoward medical event that occurs in a participant administered an investigational product and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product. TEAEs were defined as adverse events with onset or worsening on or after date of first dose of study treatment.

Original Primary Outcome Measures (submitted: March 21, 2018)

• Phase 1b: Percentage of Participants with Dose-Limiting Toxicity (DLT) [ Time Frame: Approximately up to 8 weeks ]
  The Dose Limiting Toxicities (DLTs) are based on drug related adverse events and defined as any of the following events: hematological / non hematological toxicity of Grade 3 or higher.
• Phase 1b: Number of Participants with Adverse Events (AEs) [ Time Frame: Approximately up to 2 years ]
  An AE is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.
• Phase 2: Overall Response Rate (ORR) (Partial Response [PR] or Better) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 [ Time Frame: Approximately up to 2 years ]
  ORR is defined as the percentage of participants with PR or complete response (CR) as defined by RECIST 1.1, as assessed by the investigator.
• Phase 2: Number of Participants with AEs [ Time Frame: Approximately up to 2 years ]
  An AE is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.

Current Secondary Outcome Measures (submitted: September 29, 2023)

• Phase 1b and Phase 2: Plasma Concentration of Erdafitinib [ Time Frame: Up to 6 years 1 month ]
• Phase 1b and Phase 2: Serum Concentration of Cetrelimab [ Time Frame: Up to 6 years 1 month ]
• Phase 1b: Plasma Concentration of Platinum (Cisplatin and Carboplatin) Chemotherapy [ Time Frame: Up to 6 years 1 month ]
• Phase 1b and Phase 2: Number of Participants With Anti-Cetrelimab Antibodies [ Time Frame: Up to 6 years 1 month ]
• Phase 2: Number of Participants With Serious Adverse Events (SAEs) [ Time Frame: Up to 6 years 1 month ]
• Phase 2: Number of Participants With Abnormal Laboratory Values [ Time Frame: Up to 6 years 1 month ]
• Phase 2: Duration of Response (DoR) [ Time Frame: Up to 6 years 1 month ]
• Phase 2: Time to Response (TTR) [ Time Frame: Up to 6 years 1 month ]
• Phase 2: Progression-free Survival (PFS) [ Time Frame: Up to 6 years 1 month ]
• Phase 2: Overall Survival (OS) [ Time Frame: Up to 6 years 1 month ]

Original Secondary Outcome Measures (submitted: March 21, 2018)

• Phase 1b and Phase 2: Plasma Concentration of Erdafitinib [ Time Frame: Cycle(C)1 Day(D)1 up to C3D1 (each cycle of 28 days) ]
  Plasma concentrations will be reported for erdafitinib.
• Phase 1b and Phase 2: Serum Concentration of JNJ-63723283 [ Time Frame: Up to Follow-up (approximately up to 2 years) ]
  Serum concentrations will be reported for JNJ-63723283.
• Phase 1b and Phase 2: Number of Participants with Anti-JNJ-63723283 Antibodies [ Time Frame: Up to Follow-up (approximately up to 2 years) ]
  Number of participants with anti-JNJ-63723283 antibodies will be reported.
• Phase 2: Number of Participants with Serious Adverse Events (SAEs) [ Time Frame: Approximately up to 2 years ]
  An SAE is any AE that results in: death, persistent or significant disability/incapacity, requires inpatient hospitalization or prolongation of existing hospitalization, is life-threatening experience, is a congenital anomaly/birth defect and may jeopardize participant and/or may require medical or surgical intervention to prevent one of the outcomes listed above.
• Phase 2: Number of Participants with Abnormal Laboratory Values [ Time Frame: Approximately up to 2 years ]
  Number of participants with abnormal laboratory values will be reported.
• Phase 2: Duration of Response (DoR) [ Time Frame: Approximately up to 2 years ]
  DoR is defined as the time from the date of initial documentation of a response (CR or PR) to the date of first documented evidence of progressive disease (or relapse for participants who experience CR during the study) or death.
• Phase 2: Time to Response (TTR) [ Time Frame: Approximately up to 2 years ]
  TTR is defined as the time from the date of randomization to the date of initial documentation of a response (CR or PR).
• Phase 2: Progression-Free Survival (PFS) [ Time Frame: Approximately up to 2 years ]
  PFS is defined as the duration from the date of randomization until the date of first documented evidence of progressive disease (or relapse for participants who experience CR during the study) or death, whichever comes first.
• Phase 2: Overall Survival (OS) [ Time Frame: Approximately up to 2 years ]
  OS is defined as the time from the date of randomization to the date of the participant's death.
• Phase 2: Overall Response Rate (ORR) per Immune-Related RECIST (iRECIST) Criteria [ Time Frame: Approximately up to 2 years ]
  ORR is defined as the percentage of participants who achieve CR or PR, as defined by iRECIST, as assessed by the investigator.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study of Erdafitinib in Participants With Metastatic or Locally Advanced Urothelial Cancer
• Official Title: A Phase 1b-2 Study to Evaluate Safety, Efficacy, Pharmacokinetics, and Pharmacodynamics of Various Regimens of Erdafitinib in Subjects With Metastatic or Locally Advanced Urothelial Cancer
• Brief Summary: The purpose of this study is to: (a) characterize the safety and tolerability of and to identify the recommended Phase 2 dose (RP2D) and schedule for erdafitinib in combination with cetrelimab, and for erdafitinib in combination with cetrelimab and platinum (cisplatin and carboplatin) chemotherapy and; (b) to evaluate the safety and clinical activity of erdafitinib alone and in combination with cetrelimab in cisplatin-ineligible participants with metastatic or locally advanced urothelial cancer (UC) with select fibroblast growth factor receptor (FGFR) gene alterations and no prior systemic therapy for metastatic disease.
• Detailed Description: This open-label (all people know identity of intervention) and multicenter (when more than one hospital or medical school team work on a medical research study) study to establish the recommended phase 2 dose (RP2D) for erdafitinib and cetrelimab and/or platinum (cisplatin or carboplatin) chemotherapy, and to evaluate the safety of erdafitinib in combination with cetrelimab and platinum chemotherapy in Phase 1b and to evaluate the safety and efficacy of the RP2D of erdafitinib plus cetrelimab versus erdafitinib in Phase 2 in participants with advanced urothelial cancer with select fibroblast growth factor receptor (FGFR) gene alterations. Participants enrolled in Phase 1b erdafitinib + cetrelimab cohort may have received any number of lines of prior therapy, and participants enrolled in Phase 1b erdafitinib + cetrelimab + platinum chemotherapy cohort will have had no prior systemic therapy for metastatic disease and participants enrolled in Phase 2 will have had no prior systemic therapy for metastatic disease and will be cis-ineligible. Part 1 (Phase 1b: Dose Escalation) will identify safety and RP2Ds of erdafitinib + cetrelimab and erdafitinib + cetrelimab + platinum (cisplatin or carboplatin) chemotherapy, and Part 2 (Phase 2: Dose Expansion) will evaluate erdafitinib monotherapy and the RP2D regimen of the erdafitinib + cetrelimab combination to further characterize safety and clinical activity. The study will be conducted in 3 phases: screening phase, treatment phase, and follow-up phase. Study evaluations include efficacy, pharmacokinetics, pharmacodynamics, immunogenicity, biomarkers, and safety.
• Study Type: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Sequential Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Urothelial Carcinoma

Intervention

• Drug: Erdafitinib
  Participants will receive erdafitinib orally.
  Other Name: JNJ-42756493
• Drug: Cetrelimab
  Participants will receive cetrelimab by intravenous infusion.
  Other Name: JNJ-63723283
• Drug: Cisplatin
  Participants will receive cisplatin by intravenous infusion as a part of platinum chemotherapy.
• Drug: Carboplatin
  Participants will receive carboplatin by intravenous infusion as a part of platinum chemotherapy.

Study Arms

• Experimental: Phase 1b: Dose Escalation
  Two dosing cohorts (erdafitinib and cetrelimab; and erdafitinib, cetrelimab and cisplatin/carboplatin) are explored in Phase 1b of the study. Participants will receive erdafitinib orally followed by cetrelimab intravenously (IV) and carboplatin/cisplatin IV as a part of platinum chemotherapy. The dose levels will be escalated sequentially based on the decisions of the Study Evaluation Team (SET) until the recommended Phase 2 Dose (RP2D) has been identified.
  Interventions:

  • Drug: Erdafitinib
  • Drug: Cetrelimab
  • Drug: Cisplatin
  • Drug: Carboplatin
• Experimental: Phase 2: Dose Expansion
  The participants will be randomized in a 1:1 manner to receive either erdafitinib alone (orally) or the identified RP2D of Phase 1b for erdafitinib (orally) in combination with cetrelimab (IV).
  Interventions:

  • Drug: Erdafitinib
  • Drug: Cetrelimab

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: October 5, 2022): 125
• Original Estimated Enrollment (submitted: March 21, 2018): 102
• Estimated Study Completion Date: June 30, 2025
• Actual Primary Completion Date: September 30, 2022 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Histologic demonstration of transitional cell carcinoma of the urothelium. Variant urothelial carcinoma histologies such as glandular or squamous differentiation, or evolution to more aggressive phenotypes such as sarcomatoid or micropapillary change are acceptable
• Metastatic or locally advanced urothelial cancer
• Must have measurable disease by radiological imaging according to the Response Evaluation Criteria in Solid Tumors (RECIST, version 1.1) at baseline
• Prior systemic therapy for metastatic urothelial cancer: (a) For Phase 1b erdafitinib + cetrelimab cohort: Any number of lines of prior therapy; (b) For Phase 1b erdafitinib + cetrelimab + platinum chemotherapy cohort: No prior systemic therapy for metastatic disease; and renal function for participants must have a creatinine clearance (CrCl) greater than (>) 30 milliliter per minute (mL/min) to receive carboplatin and >60 mL/min to receive cisplatin as calculated by Cockcroft Gault and (c) Phase 2: No prior systemic therapy for metastatic disease and cisplatin-ineligible based on: ECOG PS 0-1 and at least one of the following criteria: Renal function defined as creatinine clearance (CrCl) less than (˂) 60 mL/min as calculated by Cockcroft-Gault; Grade 2 or higher peripheral neuropathy per NCI-CTCAE version 5.0; Grade 2 or higher hearing loss per NCI-CTCAE version 5.0 OR ECOG PS 2
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) grade of: (a) Phase 1b erdafitinib + cetrelimab cohort: ECOG 0-2; (b) Phase 1b erdafitinib + cetrelimab + platinum chemotherapy cohort: ECOG 0-1 for cisplatin and 0-2 for carboplatin (c) Phase 2: ECOG 0-2

Exclusion Criteria:

• Treatment with any other investigational agent or participation in another clinical study with therapeutic intent within 30 days prior to Cycle 1 Day 1. For Phase 1b, participants who have received the following prior antitumor therapy: received nitrosoureas and mitomycin C within 6 weeks
• Phase 1b erdafitinib + cetrelimab cohort: Chemotherapy within 3 weeks of Cycle 1 Day 1; Phase 1b erdafitinib + cetrelimab + platinum chemotherapy cohort and Phase 2: Prior neoadjuvant/adjuvant chemotherapy is allowed if the last dose was given >12 months prior to recurrent disease progression and did not result in drug-related toxicity leading to treatment discontinuation
• Prior anti-programmed death receptor-1 (PD-1), anti-programmed death ligand-1 (PD-L1), or anti-programmed death ligand-2 (PD-L2) therapy. Prior neoadjuvant/adjuvant checkpoint inhibitor therapy is allowed if the last dose was given more than (>)12 months prior to recurrent disease progression and did not result in drug-related toxicity leading to treatment discontinuation. PD-1 for non-muscle invasive bladder cancer is also allowed
• Active malignancies requiring concurrent therapy other than urothelial cancer
• Symptomatic central nervous system metastases

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Belarus, Belgium, Brazil, France, Italy, Korea, Republic of, Poland, Russian Federation, Spain, Taiwan, Turkey, United Kingdom, United States
• Removed Location Countries: Georgia

Administrative Information

• NCT Number: NCT03473743
• Other Study ID Numbers: CR108445; 2017-001980-19 ( EudraCT Number ); 42756493BLC2002 ( Other Identifier: Janssen Research & Development, LLC ); 2023-510295-31-00 ( Registry Identifier: EUCT number )
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Janssen Research & Development, LLC
• Original Responsible Party: Same as current
• Current Study Sponsor: Janssen Research & Development, LLC
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Janssen Research & Development, LLC Clinical Trial; Janssen Research & Development, LLC

• PRS Account: Janssen Research & Development, LLC
• Verification Date: April 2024