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A Study to Evaluate Safety, Efficacy, Pharmacokinetics, and Pharmacodynamics of Erdafitinib Plus JNJ-63723283 (Cetrelimab), an Anti-PD-1 Monoclonal Antibody, in Participants With Metastatic or Locally Advanced Urothelial Cancer With Selected FGFR Gene Alterations

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ClinicalTrials.gov Identifier: NCT03473743
Recruitment Status : Recruiting
First Posted : March 22, 2018
Last Update Posted : May 20, 2020
Sponsor:
Information provided by (Responsible Party):
Janssen Research & Development, LLC

Brief Summary:
The purpose of this study is to identify the recommended Phase 2 dose (RP2D) and schedule of erdafitinib in combination with cetrelimab (Phase 1b) and to evaluate the safety and clinical activity of erdafitinib alone and in combination with cetrelimab in first line metastatic urothelial carcinoma (mUC) setting (Phase 2).

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

Expanded Access : An investigational treatment associated with this study has been approved for sale to the public.   More info ...

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 of erdafitinib plus cetrelimab in participants with advanced urothelial cancer with selected fibroblast growth factor receptor (FGFR) gene alterations, will consists of 2 parts. Participants enrolled in Part 1 may have received any number of lines of prior therapy, and participants enrolled in Part 2 will have had no prior systemic therapy for metastatic disease and cis-ineligible. Part 1 (Phase 1b: Dose Escalation) will establish recommended Phase 2 dose (RP2D) for erdafitinib in combination with cetrelimab, and Part 2 (Phase 2: Dose Expansion) will evaluate safety and efficacy of RP2D. 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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 150 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 Erdafitinib Plus JNJ-63723283 (Cetrelimab), an Anti-PD-1 Monoclonal Antibody, in Subjects With Metastatic or Locally Advanced Urothelial Cancer With Selected FGFR Gene Alterations
Actual Study Start Date : April 5, 2018
Estimated Primary Completion Date : June 17, 2021
Estimated Study Completion Date : September 22, 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Phase 1b: Dose Escalation
Two dosing cohorts (standard and alternative) are explored in Phase 1b of the study. The participants will receive erdafitinib orally, 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. Whereas, the participants will receive a fixed dose of cetrelimab intravenously (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

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




Primary Outcome Measures :
  1. 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.

  2. 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.

  3. 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: 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.

  4. 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.


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: 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.

  5. 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.

  6. 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.

  7. 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).

  8. 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.

  9. 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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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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) Phase 1b: Any number of lines of prior therapy; (b) Phase 2: No prior systemic therapy for metastatic disease and cisplatin-ineligible
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) grade of: 0, 1, or 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
  • Chemotherapy within 3 weeks of Cycle 1 Day 1
  • 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
  • Active malignancies requiring concurrent therapy other than urothelial cancer
  • Symptomatic central nervous system metastases

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
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: May 20, 2020
Last Verified: May 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