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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

Sponsor
Janssen Research & Development, LLC (Industry)
Overall Status
Completed
CT.gov ID
NCT03551782
Collaborator
(none)
33
Enrollment
34
Locations
5
Arms
40.5
Actual Duration (Months)
1
Patients Per Site
0
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease Intervention/Treatment Phase
  • Drug: Cetrelimab 480 mg
  • Drug: Apalutamide 240 mg
 Phase 1

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, darolutamide, 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 an Optional Pre-screening Period, 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.

Study Design

Study Type:
Interventional
Actual Enrollment :
33 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
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
Actual Study Start Date :
Jun 28, 2018
Actual Primary Completion Date :
Nov 11, 2021
Actual Study Completion Date :
Nov 11, 2021

Arms and Interventions

Arm Intervention/Treatment
Experimental: Cohort 1

Biomarker-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).

Drug: Cetrelimab 480 mg
Cetrelimab 480 mg will be administered intravenously (IV) on Cycle 1 Day 1, then every 4 weeks thereafter (Q4W).
Other Names:
  • JNJ-63723283

    • Drug: Apalutamide 240 mg
    Apalutamide 240 mg (4*60 mg) tablets per day will be administered orally.
    Other Names:
  • JNJ-56021927

    		•
    Experimental: Cohort 2

    Biomarker-negative or biomarker-unknown participants with adenocarcinoma (and not t-SCNC) who progressed on apalutamide, darolutamide, or enzalutamide will be enrolled in this cohort. Participants will receive cetrelimab 480 mg plus apalutamide 240 mg daily starting Cycle 1.

    Drug: Cetrelimab 480 mg
    Cetrelimab 480 mg will be administered intravenously (IV) on Cycle 1 Day 1, then every 4 weeks thereafter (Q4W).
    Other Names:
  • JNJ-63723283

    • Drug: Apalutamide 240 mg
    Apalutamide 240 mg (4*60 mg) tablets per day will be administered orally.
    Other Names:
  • JNJ-56021927

    		•
    Experimental: Cohort 3

    Biomarker-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).

    Drug: Cetrelimab 480 mg
    Cetrelimab 480 mg will be administered intravenously (IV) on Cycle 1 Day 1, then every 4 weeks thereafter (Q4W).
    Other Names:
  • JNJ-63723283

    • Drug: Apalutamide 240 mg
    Apalutamide 240 mg (4*60 mg) tablets per day will be administered orally.
    Other Names:
  • JNJ-56021927

    		•
    Experimental: Cohort 4

    Biomarker-positive participants who progressed on apalutamide, darolutamide, 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).

    Drug: Cetrelimab 480 mg
    Cetrelimab 480 mg will be administered intravenously (IV) on Cycle 1 Day 1, then every 4 weeks thereafter (Q4W).
    Other Names:
  • JNJ-63723283

    • Drug: Apalutamide 240 mg
    Apalutamide 240 mg (4*60 mg) tablets per day will be administered orally.
    Other Names:
  • JNJ-56021927

    		•
    Experimental: Cohort 5

    Biomarker-negative participants with t-SCNC who progressed on treatment with AA-P, apalutamide, darolutamide, 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).

    Drug: Cetrelimab 480 mg
    Cetrelimab 480 mg will be administered intravenously (IV) on Cycle 1 Day 1, then every 4 weeks thereafter (Q4W).
    Other Names:
  • JNJ-63723283

    • Drug: Apalutamide 240 mg
    Apalutamide 240 mg (4*60 mg) tablets per day will be administered orally.
    Other Names:
  • JNJ-56021927

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Number of Participants With Adverse Events (AEs) [Approximately 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.

    2. Number of Participants with AEs by Severity [Approximately 2 years]

      Severity of AEs will be assessed using National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE). Any AE not listed in the NCI CTCAE will be graded according to the investigator clinical judgment by using the standard grades as follows: Grade 1 Mild: Awareness of symptoms that are easily tolerated, causing minimal discomfort and not interfering with everyday activities; Grade 2 Moderate: Sufficient discomfort is present to cause interference with normal activity; Grade 3 Severe: Extreme distress, causing significant impairment of functioning or incapacitation. Prevents normal everyday activities; Grade 4: Life-threatening or disabling AE; Grade 5: Death related to the AE.

    3. Percentage of Participants with Prostate-Specific Antigen (PSA) Response at Week 12 [Week 12]

      Percentage of participants with baseline in PSA level response (greater than or equal to [>=]50 percent [%] decrease from baseline in PSA) will be reported at Week 12.

    Secondary Outcome Measures

    1. Maximal PSA Decline [Approximately 2 years]

      Maximal PSA decline is defined as maximal percent decrease in PSA at any time during treatment.

    2. Percentage of Participants with Circulating Tumor Cell (CTC) Response [Approximately 2 years]

      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.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    Male
    Accepts Healthy Volunteers:
    No
    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, darolutamide, 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, darolutamide, or enzalutamide; Cohort 3: Biomarker-positive participants who progressed on AA-P; Cohort 4: Biomarker-positive participants who progressed on apalutamide, darolutamide, or enzalutamide; Cohort 5: Biomarker-negative participants with t-SCNC who progressed on treatment with AA-P, apalutamide, darolutamide, 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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 University of California San Francisco (UCSF) - Prostate Cancer Center San Francisco California United States 94158-2350
    2 Regional Urology LLC Shreveport Louisiana United States 71106
    3 University of Michigan Health System Ann Arbor Michigan United States 48109-5000
    4 Washington University Bay Saint Louis Mississippi United States 63110
    5 New York University Langone Medical Center New York New York United States 10016
    6 Icahn School of Medicine at Mount Sinai - The Derald H. Ruttenberg New York New York United States 10029-6542
    7 Levine Cancer Institute, Carolinas HealthCare System Charlotte North Carolina United States 28204
    8 Centers for Advanced Urology, LLC; d/b/a MidLantic Urology Bala-Cynwyd Pennsylvania United States 19004
    9 Thomas Jefferson University Philadelphia Pennsylvania United States 19107
    10 University of Texas, MD Anderson Cancer Center Houston Texas United States 77030
    11 Virginia Oncology Associates Norfolk Virginia United States 23502
    12 Grand Hôpital de Charleroi, site Notre Dame Charleroi Belgium 6000
    13 AZ Maria Middelares Gent Belgium 9000
    14 Cross Cancer Institute Edmonton Alberta Canada T6G 1Z2
    15 University of Toronto Toronto Ontario Canada M5G 2M9
    16 Centre de Recherche du CHUM Montreal Quebec Canada H2X 0A9
    17 Istituto Europeo di Oncologia Servizio Radioterapia Milano Italy 20141
    18 NKI-AVL, Amsterdam Amsterdam Netherlands 1066 CX
    19 UMC Radboud Nijmegen Netherlands 6525AG
    20 Sint Franciscus Gasthuis Rotterdam Netherlands 3045 PM
    21 Moscow City Clinical Hospital # 62 Moscow Russian Federation 125130
    22 Hertzen Oncology Research Institute Moscow Russian Federation 125284
    23 Clinical Oncology Dispensary Omsk Russian Federation 644013
    24 Non-State Healthcare Institution 'Road Clinical Hospital of Russian Railways' Saint Petersburg Russian Federation 195271
    25 Russian Scientific Center of Radiology and Surgical Technologies Sankt-Peterburg Russian Federation 197758
    26 Hosp. Univ. Vall D Hebron Barcelona Spain 8035
    27 Hosp. Gral. Univ. Gregorio Marañon Madrid Spain 28009
    28 Hosp. Univ. Ramon Y Cajal Madrid Spain 28034
    29 Hosp. Univ. Fund. Jimenez Diaz Madrid Spain 28040
    30 Hosp. Univ. Hm Sanchinarro Madrid Spain 28050
    31 Hosp. Virgen de La Victoria Málaga Spain 29010
    32 Hosp. Quiron Madrid Pozuelo Pozuelo de Alarcon Spain 28223
    33 Hosp. Univ. Marques de Valdecilla Santander Spain 39008
    34 Instituto Valenciano de Oncologia Valencia Spain 46009

    Sponsors and Collaborators

    • Janssen Research & Development, LLC

    Investigators

    • Study Director: Janssen Research & Development, LLC Clinical Trial, Janssen Research & Development, LLC

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Janssen Research & Development, LLC
    ClinicalTrials.gov Identifier:
    NCT03551782
    Other Study ID Numbers:
    • CR108476
    • 2018-000182-37
    • 56021927PCR2032
    First Posted:
    Jun 11, 2018
    Last Update Posted:
    Feb 25, 2022
    Last Verified:
    Feb 1, 2022
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:
    Prostatic Neoplasms
    Prostatic Neoplasms, Castration-Resistant

    Study Results

    No Results Posted as of Feb 25, 2022