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A Study of Cetrelimab (JNJ-63723283), a Programmed Cell Death Receptor-1 (PD-1) Inhibitor, Administered in Combination With Apalutamide in Participants With Metastatic Castration-Resistant Prostate Cancer

NCT03551782

Description:

The purpose of this study is to evaluate the safety of the combination of cetrelimab, with apalutamide and to define a population of participants with metastatic castration-resistant prostate cancer (mCRPC) who respond to treatment with the combination of cetrelimab and apalutamide.

Related Conditions:
  • Prostate Adenocarcinoma
  • Prostate Small Cell Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Study of Cetrelimab (JNJ-63723283), a Programmed Cell Death Receptor-1 (PD-1) Inhibitor, Administered in Combination With Apalutamide in Participants With Metastatic Castration-Resistant Prostate Cancer
  • Official Title: An Open-label, Multicenter, Phase 1b Study of JNJ-63723283, a PD-1 Inhibitor, Administered in Combination With Apalutamide in Subjects With Metastatic Castration-Resistant Prostate Cancer

Clinical Trial IDs

  • ORG STUDY ID: CR108476
  • SECONDARY ID: 2018-000182-37
  • SECONDARY ID: 56021927PCR2032
  • NCT ID: NCT03551782

Conditions

  • Castration-Resistant Prostatic Neoplasms

Interventions

DrugSynonymsArms
Cetrelimab 480 mgJNJ-63723283Cohort 1
Apalutamide 240 mgJNJ-56021927Cohort 1

Purpose

The purpose of this study is to evaluate the safety of the combination of cetrelimab, with apalutamide and to define a population of participants with metastatic castration-resistant prostate cancer (mCRPC) who respond to treatment with the combination of cetrelimab and apalutamide.

Detailed Description

      This study is of participants originally diagnosed with adenocarcinoma of the prostate who
      have now developed mCRPC and who have progressed on therapy with abiraterone acetate plus
      prednisone/prednisolone (AA-P), apalutamide, or enzalutamide. Participants with
      treatment-emergent small-cell neuroendocrine prostate cancer (t-SCNC) assessed by the
      screening biopsy may be considered for this study. Participants must have confirmed
      prostate-specific antigen (PSA) progression per Prostate Cancer Clinical Trials Working Group
      (PCWG3) criteria. The primary hypothesis is that treatment with cetrelimab and apalutamide is
      safe and leads to improvement in the 12-week PSA response rate. The study consists of
      Screening period (28 days prior to Cycle 1 Day 1), Treatment Period, End-of-Treatment Visit
      (performed after the last dose of study drug is administered), and Follow-up Period
      (participants will have Follow-up assessment every 12 weeks after the End-of-Treatment
      Visit). The efficacy, safety, and pharmacokinetics of cetrelimab in combination with
      apalutamide will be evaluated.
    

Trial Arms

NameTypeDescriptionInterventions
Cohort 1ExperimentalBiomarker-negative or biomarker-unknown participants with adenocarcinoma (and not treatment-emergent small-cell neuroendocrine prostate cancer [t-SCNC]) who progressed on abiraterone acetate plus prednisone/prednisolone (AA-P) will be enrolled in this cohort. Participants will receive cetrelimab 480 milligram (mg) plus apalutamide 240 mg daily starting Cycle 1 (each cycle of 28 days).
  • Cetrelimab 480 mg
  • Apalutamide 240 mg
Cohort 2ExperimentalBiomarker-negative or biomarker-unknown participants with adenocarcinoma (and not t-SCNC) who progressed on apalutamide or enzalutamide will be enrolled in this cohort. Participants will receive cetrelimab 480 mg plus apalutamide 240 mg daily starting Cycle 1.
  • Cetrelimab 480 mg
  • Apalutamide 240 mg
Cohort 3ExperimentalBiomarker-positive participants who progressed on AA-P will be enrolled in this cohort. Participants will receive cetrelimab 480 mg plus apalutamide 240 mg daily starting Cycle 1 (each cycle of 28 days).
  • Cetrelimab 480 mg
  • Apalutamide 240 mg
Cohort 4ExperimentalBiomarker-positive participants who progressed on apalutamide or enzalutamide will be enrolled in this cohort. Participants will receive cetrelimab 480 mg plus apalutamide 240 mg daily starting Cycle 1 (each cycle of 28 days).
  • Cetrelimab 480 mg
  • Apalutamide 240 mg
Cohort 5ExperimentalBiomarker-negative participants with t-SCNC who progressed on treatment with AA-P, apalutamide or enzalutamide will be enrolled in this cohort. Participants will receive cetrelimab 480 mg plus apalutamide 240 mg daily starting Cycle 1 (each cycle of 28 days).
  • Cetrelimab 480 mg
  • Apalutamide 240 mg

Eligibility Criteria

        Inclusion Criteria:

          -  Pathologically confirmed adenocarcinoma of the prostate. Treatment-emergent small-cell
             neuroendocrine prostate cancer (t-SCNC) on screening biopsy may be eligible for cohort
             5

          -  Metastatic disease as documented by technetium-99m (99mTc) bone scan or metastatic
             lesions by computed tomography (CT) or magnetic resonance imaging (MRI) scans
             (visceral or lymph node disease). CT-portion of positron emission tomography (PET)/CT
             scan may be used for eligibility. If lymph node metastasis is the only evidence of
             metastatic disease, it must be greater than (>=) 1.0 centimeter (cm) in the short axis
             and above the level of the iliac bifurcation

          -  Progressed while on therapy with abiraterone acetate plus prednisone/prednisolone
             (AA-P), enzalutamide or apalutamide for mCRPC. No washout is required and no
             additional therapy may have been administered between discontinuation of AR-targeted
             the agent and study treatment. Participants will be assigned to cohorts based on the
             results of the biomarker panel. Cohort 1: Biomarker-negative or biomarker-unknown
             participants with adenocarcinoma (and not t-SCNC) who progressed on abiraterone
             acetate plus prednisone/prednisolone (AA-P); Cohort 2: Biomarker-negative or
             biomarker-unknown participants with adenocarcinoma (and not t-SCNC) who progressed on
             apalutamide or enzalutamide; Cohort 3: Biomarker-positive participants who progressed
             on AA-P; Cohort 4: Biomarker-positive participants who progressed on apalutamide or
             enzalutamide; Cohort 5: Biomarker-negative participants with t-SCNC who progressed on
             treatment with AA-P, apalutamide or enzalutamide

          -  Surgical or medical castration, with testosterone levels of less than (<)50 nanogram
             per deciliter (ng/dL). If the participant is being treated with gonadotropin-releasing
             hormone (GnRH) analogs (participant who has not undergone bilateral orchiectomy), this
             therapy must have been initiated at least 4 weeks prior to first dose of study drug
             and must be continued throughout the study

          -  Eastern Cooperative Oncology Group Performance Status (ECOG) prostate-specific (PS)
             grade of 0 or 1

        Exclusion Criteria:

          -  Initial diagnosis of primary prostatic neuroendocrine or small cell carcinoma

          -  Brain metastases

          -  Prior treatment with an anti-programmed cell death receptor-1 (PD-1), anti-programmed
             cell death ligand 1 (PD-L1), or anti-cytotoxic T-lymphocyte antigen 4 (CTLA-4)
             antibody

          -  Prior chemotherapy, except for docetaxel for hormone-sensitive prostate cancer (HSPC)

          -  Prior therapy with poly adenosine diphosphate (ADP)-ribose polymerase (PARP)
             inhibitors
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Male
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number of Participants With Adverse Events (AEs)
Time Frame:Approximately 2 years
Safety Issue:
Description: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

Measure:Maximal PSA Decline
Time Frame:Approximately 2 years
Safety Issue:
Description:Maximal PSA decline is defined as maximal percent decrease in PSA at any time during treatment.
Measure:Percentage of Participants with Circulating Tumor Cell (CTC) Response
Time Frame:Approximately 2 years
Safety Issue:
Description:Percentage of participants with CTC response (either CTC less than [<]5 cells/7.5 milliliter [mL] with CTC >=5 at baseline or CTC = 0 cells/7.5 mL with CTC >=1 at baseline) will be reported.

Details

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

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