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

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

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.

Study Overview

• Status: Completed
• Conditions: Castration-Resistant Prostatic Neoplasms
• Intervention / Treatment: Drug: Cetrelimab 480 mg; Drug: Apalutamide 240 mg

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 Type: Interventional
• Enrollment (Actual): 33
• Phase: Phase 1

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Adverse Events (AEs)	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.	Approximately 2 years
Number of Participants with AEs by Severity	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.	Approximately 2 years
Percentage of Participants with Prostate-Specific Antigen (PSA) Response at 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.	Week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximal PSA Decline	Maximal PSA decline is defined as maximal percent decrease in PSA at any time during treatment.	Approximately 2 years
Percentage of Participants with Circulating Tumor Cell (CTC) Response	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.	Approximately 2 years

Collaborators and Investigators

• Sponsor: Janssen Research & Development, LLC

Study record dates

Study Major Dates

• Study Start (Actual): June 28, 2018
• Primary Completion (Actual): November 11, 2021
• Study Completion (Actual): November 11, 2021

Study Registration Dates

• First Submitted: May 30, 2018
• First Submitted That Met QC Criteria: May 30, 2018
• First Posted (Actual): June 11, 2018

Study Record Updates

• Last Update Posted (Actual): February 25, 2022
• Last Update Submitted That Met QC Criteria: February 24, 2022
• Last Verified: February 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Prostatic Neoplasms; Prostatic Neoplasms, Castration-Resistant
• Other Study ID Numbers: CR108476; 2018-000182-37 (EudraCT Number); 56021927PCR2032 (Other Identifier: Janssen Research & Development, LLC)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No