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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03473743
Recruitment Status : Recruiting
First Posted : March 22, 2018
Last Update Posted : September 21, 2020
Sponsor:
Information provided by (Responsible Party):
Janssen Research & Development, LLC

Study Description
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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.

Condition or disease Intervention/treatment Phase
Urothelial Carcinoma Drug: Erdafitinib Drug: Cetrelimab Drug: Cisplatin Drug: Carboplatin Phase 1 Phase 2

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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 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) in which the erdafitinib monotherapy and the RP2D regimen of the erdafitinib + cetrelimab combination are evaluated 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 Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 160 participants
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : April 5, 2018
Estimated Primary Completion Date : June 17, 2021
Estimated Study Completion Date : March 17, 2023

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Arms and Interventions
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Arm Intervention/treatment
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.
 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 cisplatin by intravenous infusion as a part of platinum chemotherapy.
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).
 Drug: Erdafitinib
Participants will receive erdafitinib orally.
Other Name: JNJ-42756493

Drug: Cetrelimab
Participants will receive cetrelimab by intravenous infusion.
Other Name: JNJ-63723283


Outcome Measures
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Primary Outcome Measures :
  1. Phase 1b: Percentage of Participants with Dose-Limiting Toxicity (DLT) [ Time Frame: 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.

  2. Phase 2: Overall Response Rate (ORR) (Partial Response [PR] or Better) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 by Investigator Assessment [ Time Frame: 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.

  3. Phase 2: Number of Participants with Adverse Event (AEs) [ Time Frame: 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.


Secondary Outcome Measures :
  1. 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.

  2. Phase 1b and Phase 2: Serum Concentration of Cetrelimab [ Time Frame: Up to Follow-up (approximately up to 2 years) ]
    Serum concentrations will be reported for cetrelimab.

  3. Phase 1b and Phase 2: Number of Participants with Anti-Cetrelimab Antibodies [ Time Frame: Up to Follow-up (approximately up to 2 years) ]
    Number of participants with anti-cetrelimab antibodies will be reported.

  4. Phase 2: Number of Participants with Serious Adverse Events (SAEs) [ Time Frame: 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.

  5. Phase 2: Number of Participants with Abnormal Laboratory Values [ Time Frame: Up to 2 years ]
    Number of participants with abnormal laboratory values will be reported.

  6. Phase 2: Duration of Response (DoR) [ Time Frame: 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.

  7. Phase 2: Time to Response (TTR) [ Time Frame: 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).

  8. Phase 2: Progression-Free Survival (PFS) [ Time Frame: 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.

  9. Phase 2: Overall Survival (OS) [ Time Frame: Up to 2 years ]
    OS is defined as the time from the date of randomization to the date of the participant's death.


Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 (>) 50 milliliter per minute (mL/min) 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) ˂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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03473743


Contacts
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Contact: Study Contact 844-434-4210 JNJ.CT@sylogent.com

Locations
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Sponsors and Collaborators
Janssen Research & Development, LLC
Investigators
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Study Director: Janssen Research & Development, LLC Clinical Trial Janssen Research & Development, LLC
More Information
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Additional Information:

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Responsible Party: Janssen Research & Development, LLC
ClinicalTrials.gov Identifier: NCT03473743    
Other Study ID Numbers: CR108445
2017-001980-19 ( EudraCT Number )
42756493BLC2002 ( Other Identifier: Janssen Research & Development, LLC )
First Posted: March 22, 2018    Key Record Dates
Last Update Posted: September 21, 2020
Last Verified: September 2020

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Carcinoma, Transitional Cell
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
 Neoplasms
Carboplatin
Antineoplastic Agents