Clinical Trials /

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

NCT03473743

Description:

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.

Related Conditions:
  • Urothelial Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • 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

Clinical Trial IDs

  • ORG STUDY ID: CR108445
  • SECONDARY ID: 2017-001980-19
  • SECONDARY ID: 42756493BLC2002
  • NCT ID: NCT03473743

Conditions

  • Urothelial Carcinoma

Interventions

DrugSynonymsArms
ErdafitinibJNJ-42756493Phase 1b: Dose Escalation
CetrelimabJNJ-63723283Phase 1b: Dose Escalation
CisplatinPhase 1b: Dose Escalation
CarboplatinPhase 1b: Dose Escalation

Purpose

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 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.
    

Trial Arms

NameTypeDescriptionInterventions
Phase 1b: Dose EscalationExperimentalTwo 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.
  • Erdafitinib
  • Cetrelimab
  • Cisplatin
  • Carboplatin
Phase 2: Dose ExpansionExperimentalThe 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).
  • Erdafitinib
  • Cetrelimab

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 (>) 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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Phase 1b: Percentage of Participants with Dose-Limiting Toxicity (DLT)
Time Frame:Up to 8 weeks
Safety Issue:
Description: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.

Secondary Outcome Measures

Measure: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)
Safety Issue:
Description:Plasma concentrations will be reported for erdafitinib.
Measure:Phase 1b and Phase 2: Serum Concentration of Cetrelimab
Time Frame:Up to Follow-up (approximately up to 2 years)
Safety Issue:
Description:Serum concentrations will be reported for cetrelimab.
Measure:Phase 1b and Phase 2: Number of Participants with Anti-Cetrelimab Antibodies
Time Frame:Up to Follow-up (approximately up to 2 years)
Safety Issue:
Description:Number of participants with anti-cetrelimab antibodies will be reported.
Measure:Phase 2: Number of Participants with Serious Adverse Events (SAEs)
Time Frame:Up to 2 years
Safety Issue:
Description: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.
Measure:Phase 2: Number of Participants with Abnormal Laboratory Values
Time Frame:Up to 2 years
Safety Issue:
Description:Number of participants with abnormal laboratory values will be reported.
Measure:Phase 2: Duration of Response (DoR)
Time Frame:Up to 2 years
Safety Issue:
Description: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.
Measure:Phase 2: Time to Response (TTR)
Time Frame:Up to 2 years
Safety Issue:
Description:TTR is defined as the time from the date of randomization to the date of initial documentation of a response (CR or PR).
Measure:Phase 2: Progression-Free Survival (PFS)
Time Frame:Up to 2 years
Safety Issue:
Description: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.
Measure:Phase 2: Overall Survival (OS)
Time Frame:Up to 2 years
Safety Issue:
Description:OS is defined as the time from the date of randomization to the date of the participant's death.

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Janssen Research & Development, LLC

Last Updated

July 24, 2020