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

NCT03473743

Description:

The purpose of this study is to identify the recommended Phase 2 dose (RP2D) and schedule of erdafitinib in combination with JNJ-63723283 (Phase 1b) and to evaluate the safety and clinical activity of erdafitinib alone and in combination with JNJ-63723283 (Phase 2).

Related Conditions:
  • Urothelial Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Study to Evaluate Safety, Efficacy, Pharmacokinetics, and Pharmacodynamics of Erdafitinib Plus JNJ-63723283, an Anti-PD-1 Monoclonal Antibody, in Participants With Metastatic or Surgically Unresectable Urothelial Cancer With Selected FGFR Gene Alterations
  • Official Title: A Phase 1b-2 Study to Evaluate Safety, Efficacy, Pharmacokinetics, and Pharmacodynamics of Erdafitinib Plus JNJ-63723283, an Anti-PD-1 Monoclonal Antibody, in Subjects With Metastatic or Surgically Unresectable Urothelial Cancer With Selected FGFR Gene Alterations

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
JNJ-63723283Phase 1b: Dose Escalation

Purpose

The purpose of this study is to identify the recommended Phase 2 dose (RP2D) and schedule of erdafitinib in combination with JNJ-63723283 (Phase 1b) and to evaluate the safety and clinical activity of erdafitinib alone and in combination with JNJ-63723283 (Phase 2).

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 JNJ-63723283 in participants with advanced urothelial cancer with selected fibroblast
      growth factor receptor (FGFR) gene alterations who have progressed on or after one or more
      prior lines of systemic therapy, will consists of 2 parts. Part 1 (Phase 1b: Dose Escalation)
      will establish recommended Phase 2 dose (RP2D) for erdafitinib in combination with
      JNJ-63723283, 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.
    

Trial Arms

NameTypeDescriptionInterventions
Phase 1b: Dose EscalationExperimentalTwo 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 JNJ-63723283 intravenously (IV).
  • Erdafitinib
  • JNJ-63723283
Phase 2: Dose ExpansionExperimentalThe participants will be randomized in a 1:2 manner to receive either erdafitinib alone (orally) or the identified RP2D of Phase 1b for erdafitinib (orally) in combination with JNJ-63723283 (IV).
  • Erdafitinib
  • JNJ-63723283

Eligibility Criteria

        Inclusion Criteria:

          -  Histologic demonstration of transitional cell carcinoma of the urothelium. Minor
             components (less than [<] 50 percent [%] overall) of variant histology such as
             glandular or squamous differentiation, or evolution to more aggressive phenotypes such
             as sarcomatoid or micropapillary change are acceptable

          -  Stage IV disease

          -  Documented progression of disease per Response Evaluation Criteria in Solid Tumors
             (RECIST) 1.1, defined as any progression that requires a change in treatment, prior to
             randomization

          -  Prior systemic therapy: (a) Phase 1b: Any number of lines of prior therapy; (b) Phase
             2: Progressed after 1 or 2 lines of prior chemotherapy

          -  Eastern Cooperative Oncology Group (ECOG) performance status (PS) grade of: 0 or 1

        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

          -  Active malignancies (that is, requiring treatment change in the last 24 months) other
             than urothelial cancer (except skin cancers within the last 24 months that are
             considered completely cured)

          -  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:Approximately 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 JNJ-63723283
Time Frame:Up to Follow-up (approximately up to 2 years)
Safety Issue:
Description:Serum concentrations will be reported for JNJ-63723283.
Measure:Phase 1b and Phase 2: Number of Participants with Anti-JNJ-63723283 Antibodies
Time Frame:Up to Follow-up (approximately up to 2 years)
Safety Issue:
Description:Number of participants with anti-JNJ-63723283 antibodies will be reported.
Measure:Phase 2: Number of Participants with Serious Adverse Events (SAEs)
Time Frame:Approximately 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:Approximately 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:Approximately 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:Approximately 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:Approximately 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:Approximately 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.
Measure:Phase 2: Overall Response Rate (ORR) per Immune-Related RECIST (iRECIST) Criteria
Time Frame:Approximately up to 2 years
Safety Issue:
Description:ORR is defined as the percentage of participants who achieve CR or PR, as defined by iRECIST, as assessed by the investigator.

Details

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

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