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A Study of TAR-200 in Combination With Cetrelimab, TAR-200 Alone, or Cetrelimab Alone in Participants With Non-Muscle Invasive Bladder Cancer (NMIBC) Unresponsive to Intravesical Bacillus Calmette-Guerin Who Are Ineligible for or Elected Not to Undergo Radical Cystectomy

NCT04640623

Description:

The purpose of this study is to evaluate the overall complete response (CR) rate in participants treated with TAR-200 in combination with cetrelimab (Cohort 1), or TAR-200 alone (Cohort 2), or cetrelimab alone (Cohort 3) with Carcinoma in Situ (CIS), with or without concomitant high-grade Ta or T1 papillary disease.

Related Conditions:
  • Bladder Urothelial Carcinoma In Situ
Recruiting Status:

Not yet recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Study of TAR-200 in Combination With Cetrelimab, TAR-200 Alone, or Cetrelimab Alone in Participants With Non-Muscle Invasive Bladder Cancer (NMIBC) Unresponsive to Intravesical Bacillus Calmette-Guerin Who Are Ineligible for or Elected Not to Undergo Radical Cystectomy
  • Official Title: Phase 2b Clinical Study Evaluating Efficacy and Safety of TAR-200 in Combination With Cetrelimab, TAR-200 Alone, or Cetrelimab Alone in Participants With High-Risk Non-Muscle Invasive Bladder Cancer (NMIBC) Unresponsive to Intravesical Bacillus Calmette-Guerin (BCG) Who Are Ineligible for or Elected Not to Undergo Radical Cystectomy

Clinical Trial IDs

  • ORG STUDY ID: CR108921
  • SECONDARY ID: 2020-002646-16
  • SECONDARY ID: 17000139BLC2001
  • NCT ID: NCT04640623

Conditions

  • Urinary Bladder Neoplasms

Interventions

DrugSynonymsArms
TAR-200JNJ-17000139, Gemcitabine-Releasing Intravesical SystemCohort 1: TAR-200 and Cetrelimab
CetrelimabJNJ-63723283Cohort 1: TAR-200 and Cetrelimab

Purpose

The purpose of this study is to evaluate the overall complete response (CR) rate in participants treated with TAR-200 in combination with cetrelimab (Cohort 1), or TAR-200 alone (Cohort 2), or cetrelimab alone (Cohort 3) with Carcinoma in Situ (CIS), with or without concomitant high-grade Ta or T1 papillary disease.

Detailed Description

      Bladder cancer is the tenth most common malignancy worldwide. The natural history of
      high-risk Non-Muscle Invasive Bladder Cancer (NMIBC) is unpredictable; rates of recurrence
      vary from 15 percent (%) to 78%, and rates of progression to muscle invasion and metastasis
      vary from less than (<) 1 to 45%. The TAR-200/gemcitabine (JNJ-17000139-AAC) product
      (hereafter, TAR-200) is an intravesical drug delivery system regulated as an investigational
      drug. The drug constituent consists of gemcitabine minitablets, and osmotic minitablets
      containing urea as the osmotic agent. Cetrelimab (JNJ-63723283) is a fully human
      immunoglobulin G4 (IgG4) kappa monoclonal antibody (mAb) that binds PD-1. This study consists
      3 periods: screening phase (up to 30 days); treatment phase (up to 2 years); follow up phase
      (up to 5 years). Total duration of study is up to 5 years. Efficacy, safety, pharmacokinetics
      (PK), and biomarkers will be assessed at specified time points during this study.
    

Trial Arms

NameTypeDescriptionInterventions
Cohort 1: TAR-200 and CetrelimabExperimentalTAR-200 is placed into the bladder through an inserter on Day 0 and will be dosed every 21 days for up to the first 24 weeks (6 months), then every 12 weeks through Week 96 (Study Year 2). In addition, Cetrelimab will be administered.
  • TAR-200
  • Cetrelimab
Cohort 2: TAR-200ExperimentalTAR-200 is placed into the bladder through an inserter on Day 0 and will be dosed every 21 days for up to the first 24 weeks (6 months), then every 12 weeks through Week 96 (Study Year 2).
  • TAR-200
Cohort 3: CetrelimabExperimentalParticipants will receive Cetrelimab.
  • Cetrelimab

Eligibility Criteria

        Inclusion Criteria:

          -  Histologically confirmed diagnosis of high-risk, non-muscle invasive urothelial
             carcinoma in situ (CIS; Tis), with or without papillary disease (T1, high-grade Ta)
             within 12 months of completion of adequate Bacillus Calmette-Guerin (BCG) therapy.
             Mixed histology tumours are allowed if urothelial differentiation (transitional cell
             histology) is predominant (example, less than (<) 20 percent (%) variant histologic
             subtype). However, the presence of neuroendocrine, micropapillary, signet ring cell,
             plasmacytoid, or sarcomatoid features will make a participant ineligible. For
             participants with lamina propria invasion (T1) on the screening biopsy/ transurethral
             resection of bladder tumor (TURBT), muscularis propria must be present in order to
             rule out Muscle Invasive Bladder Cancer (MIBC)

          -  Visible papillary disease must be fully resected (absent) prior to randomization
             (residual CIS acceptable) and documented at screening cystoscopy

          -  Participants must be ineligible for or have elected not to undergo radical cystectomy

          -  BCG-unresponsive high-risk NMIBC after treatment with adequate BCG therapy defined as
             a minimum of 5 of 6 doses of an induction course (adequate induction) plus 2 of 3
             doses of a maintenance course, or 2 of 6 doses of a second induction course

          -  Eastern Cooperative Oncology Group (ECOG) performance status Grade 0, 1, or 2

        Exclusion Criteria:

          -  Histologically confirmed, muscle-invasive, locally advanced, nonresectable, or
             metastatic urothelial carcinoma (that is, T2, T3, T4, and/or Stage IV

          -  Concurrent extra-vesical (that is, urethra, ureter, or renal pelvis) non-muscle
             invasive transitional cell carcinoma of the urothelium

          -  Participants with an active, known or suspected autoimmune disease. Participants with
             autoimmune disorders not requiring systemic treatment (example, skin conditions such
             as vitiligo, psoriasis, alopecia) or conditions requiring hormonal replacement
             therapies such as type 1 diabetes mellitus or hypothyroidism are permitted to enroll

          -  Known active hepatitis B or C infection (for example, participants with history of
             hepatitis C infection but normal hepatitis C virus polymerase chain reaction test and
             participants with hepatitis B with positive hepatitis B surface antigen (HBsAg)
             antibody are allowed)

          -  Prior therapy with an anti-programmed cell death 1 (PD-1), anti-PD-ligand 2 (L2)
             agent, or with an agent directed to another co-inhibitory T-cell receptor
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Overall Clinical Response (CR) Rate
Time Frame:Up to 5 years
Safety Issue:
Description:Overall CR rate, is defined as the percentage of participants achieving a CR at any time post-treatment. It will be measured by determining the percentage of participants without presence of high-grade disease using results from cystoscopy and centrally read urine cytology at any time point.

Secondary Outcome Measures

Measure:Durability of Response (DOR)
Time Frame:Up to 5 years
Safety Issue:
Description:DOR is defined from the time of first CR achieved to first evidence of recurrence or progression or death (whichever is earlier) for participants who achieve a CR.
Measure:Overall Survival (OS)
Time Frame:Up to 5 years
Safety Issue:
Description:OS, defined as the time from first dose of study treatment to death; if a participant has not died at the time of analysis, the participant will be censored at the date last known alive.
Measure:Cohort 1 and 2: Concentrations of Gemcitabine and 2',2' difluorodeoxyuridine (dFdU) in Urine and Plasma
Time Frame:Up to Week 21
Safety Issue:
Description:Concentrations of gemcitabine and its metabolite dFdU in urine and plasma will be assessed.
Measure:Cohort 1 and 3: Serum Concentration of Anti-cetrelimab Antibodies
Time Frame:Predose, up to 3 years
Safety Issue:
Description:Serum concentration of anti-cetrelimab antibodies will be assessed using a validated immunoassay for anti-drug antibody (ADA) analysis.
Measure:Number of Participants with Anti-cetrelimab Antibodies
Time Frame:Predose, up to 3 years
Safety Issue:
Description:Number of participants with anti-cetrelimab antibodies will be reported.
Measure:Change from Baseline in European Organisation for Research and Treatment of Cancer Quality-of-life Questionnaire (EORTC QLQ) -C30 Scores
Time Frame:Baseline, up to 3 years and 4 months
Safety Issue:
Description:EORTC QLQ-C30 is a core 30-item questionnaire for evaluating the health-related quality of life (HRQoL) of participants participating in cancer clinical studies. It incorporates 5 functional scales (physical, role, cognitive, emotional, and social functioning), 3 symptom scales (fatigue, pain, and nausea or vomiting), and a global health status or HRQoL scale. Ratings for each item range from 1 (not at all) to 4 (very much).
Measure:Change from Baseline in EORTC QLQ- Non-Muscle-Invasive Bladder Cancer (NMIBC) 24 Scores
Time Frame:Baseline, up to 3 years and 4 months
Safety Issue:
Description:EORTC QLQ-NMIBC24 is a 24-item questionnaire for evaluating the HRQoL of participants with superficial (non-muscle-invasive) bladder cancer. The questionnaire is designed to supplement the QLQ-C30 and incorporates 6 multi-item scales and 5 single items. Ratings for each item range from 1 (not at all) to 4 (very much).
Measure:Number of Participants with Adverse Events (AEs) by Severity Grades
Time Frame:Up to 5 years
Safety Issue:
Description:An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. Severity grades ranges from Grade 1 (Mild) to Grade 5 (Death). Grade 1= Mild, Grade 2= Moderate, Grade 3= Severe, Grade 4= Life-threatening and Grade 5= Death related to adverse event.
Measure:Number of Product Quality Complaints (PQC)
Time Frame:Up to 3 years and 1 month
Safety Issue:
Description:A PQC is defined as any suspicion of a product defect related to manufacturing, labeling, or packaging, that is, any dissatisfaction relative to the identity, quality, durability, reliability, or performance of a distributed product, including its labeling, drug delivery system, or package integrity.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Janssen Research & Development, LLC

Last Updated

November 23, 2020