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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

Primary Purpose

Castration-Resistant Prostatic Neoplasms

Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
Cetrelimab 480 mg
Apalutamide 240 mg
Sponsored by
Janssen Research & Development, LLC
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Castration-Resistant Prostatic Neoplasms

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)MaleDoes not accept healthy volunteers

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

Sites / Locations

  • University of California San Francisco (UCSF) - Prostate Cancer Center
  • Regional Urology LLC
  • University of Michigan Health System
  • Washington University
  • New York University Langone Medical Center
  • Icahn School of Medicine at Mount Sinai - The Derald H. Ruttenberg
  • Levine Cancer Institute, Carolinas HealthCare System
  • Centers for Advanced Urology, LLC; d/b/a MidLantic Urology
  • Thomas Jefferson University
  • University of Texas, MD Anderson Cancer Center
  • Virginia Oncology Associates
  • Grand Hôpital de Charleroi, site Notre Dame
  • AZ Maria Middelares
  • Cross Cancer Institute
  • University of Toronto
  • Centre de Recherche du CHUM
  • Istituto Europeo di Oncologia Servizio Radioterapia
  • NKI-AVL, Amsterdam
  • UMC Radboud
  • Sint Franciscus Gasthuis
  • Moscow City Clinical Hospital # 62
  • Hertzen Oncology Research Institute
  • Clinical Oncology Dispensary
  • Non-State Healthcare Institution 'Road Clinical Hospital of Russian Railways'
  • Russian Scientific Center of Radiology and Surgical Technologies
  • Hosp. Univ. Vall D Hebron
  • Hosp. Gral. Univ. Gregorio Marañon
  • Hosp. Univ. Ramon Y Cajal
  • Hosp. Univ. Fund. Jimenez Diaz
  • Hosp. Univ. Hm Sanchinarro
  • Hosp. Virgen de La Victoria
  • Hosp. Quiron Madrid Pozuelo
  • Hosp. Univ. Marques de Valdecilla
  • Instituto Valenciano de Oncologia

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm Type

Experimental

Experimental

Experimental

Experimental

Experimental

Arm Label

Cohort 1

Cohort 2

Cohort 3

Cohort 4

Cohort 5

Arm Description

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).

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.

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).

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).

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).

Outcomes

Primary Outcome Measures

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.
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.
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.

Secondary Outcome Measures

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

Full Information

First Posted
May 30, 2018
Last Updated
February 24, 2022
Sponsor
Janssen Research & Development, LLC
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1. Study Identification

Unique Protocol Identification Number
NCT03551782
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
Study Type
Interventional

2. Study Status

Record Verification Date
February 2022
Overall Recruitment Status
Completed
Study Start Date
June 28, 2018 (Actual)
Primary Completion Date
November 11, 2021 (Actual)
Study Completion Date
November 11, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Janssen Research & Development, LLC

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Castration-Resistant Prostatic Neoplasms

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
33 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Cohort 1
Arm Type
Experimental
Arm Description
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).
Arm Title
Cohort 2
Arm Type
Experimental
Arm Description
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.
Arm Title
Cohort 3
Arm Type
Experimental
Arm Description
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).
Arm Title
Cohort 4
Arm Type
Experimental
Arm Description
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).
Arm Title
Cohort 5
Arm Type
Experimental
Arm Description
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).
Intervention Type
Drug
Intervention Name(s)
Cetrelimab 480 mg
Other Intervention Name(s)
JNJ-63723283
Intervention Description
Cetrelimab 480 mg will be administered intravenously (IV) on Cycle 1 Day 1, then every 4 weeks thereafter (Q4W).
Intervention Type
Drug
Intervention Name(s)
Apalutamide 240 mg
Other Intervention Name(s)
JNJ-56021927
Intervention Description
Apalutamide 240 mg (4*60 mg) tablets per day will be administered orally.
Primary Outcome Measure Information:
Title
Number of Participants With Adverse Events (AEs)
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.
Time Frame
Approximately 2 years
Title
Number of Participants with AEs by Severity
Description
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.
Time Frame
Approximately 2 years
Title
Percentage of Participants with Prostate-Specific Antigen (PSA) Response at Week 12
Description
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.
Time Frame
Week 12
Secondary Outcome Measure Information:
Title
Maximal PSA Decline
Description
Maximal PSA decline is defined as maximal percent decrease in PSA at any time during treatment.
Time Frame
Approximately 2 years
Title
Percentage of Participants with Circulating Tumor Cell (CTC) Response
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.
Time Frame
Approximately 2 years

10. Eligibility

Sex
Male
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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, 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Janssen Research & Development, LLC Clinical Trial
Organizational Affiliation
Janssen Research & Development, LLC
Official's Role
Study Director
Facility Information:
Facility Name
University of California San Francisco (UCSF) - Prostate Cancer Center
City
San Francisco
State/Province
California
ZIP/Postal Code
94158-2350
Country
United States
Facility Name
Regional Urology LLC
City
Shreveport
State/Province
Louisiana
ZIP/Postal Code
71106
Country
United States
Facility Name
University of Michigan Health System
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109-5000
Country
United States
Facility Name
Washington University
City
Bay Saint Louis
State/Province
Mississippi
ZIP/Postal Code
63110
Country
United States
Facility Name
New York University Langone Medical Center
City
New York
State/Province
New York
ZIP/Postal Code
10016
Country
United States
Facility Name
Icahn School of Medicine at Mount Sinai - The Derald H. Ruttenberg
City
New York
State/Province
New York
ZIP/Postal Code
10029-6542
Country
United States
Facility Name
Levine Cancer Institute, Carolinas HealthCare System
City
Charlotte
State/Province
North Carolina
ZIP/Postal Code
28204
Country
United States
Facility Name
Centers for Advanced Urology, LLC; d/b/a MidLantic Urology
City
Bala-Cynwyd
State/Province
Pennsylvania
ZIP/Postal Code
19004
Country
United States
Facility Name
Thomas Jefferson University
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19107
Country
United States
Facility Name
University of Texas, MD Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Virginia Oncology Associates
City
Norfolk
State/Province
Virginia
ZIP/Postal Code
23502
Country
United States
Facility Name
Grand Hôpital de Charleroi, site Notre Dame
City
Charleroi
ZIP/Postal Code
6000
Country
Belgium
Facility Name
AZ Maria Middelares
City
Gent
ZIP/Postal Code
9000
Country
Belgium
Facility Name
Cross Cancer Institute
City
Edmonton
State/Province
Alberta
ZIP/Postal Code
T6G 1Z2
Country
Canada
Facility Name
University of Toronto
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 2M9
Country
Canada
Facility Name
Centre de Recherche du CHUM
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H2X 0A9
Country
Canada
Facility Name
Istituto Europeo di Oncologia Servizio Radioterapia
City
Milano
ZIP/Postal Code
20141
Country
Italy
Facility Name
NKI-AVL, Amsterdam
City
Amsterdam
ZIP/Postal Code
1066 CX
Country
Netherlands
Facility Name
UMC Radboud
City
Nijmegen
ZIP/Postal Code
6525AG
Country
Netherlands
Facility Name
Sint Franciscus Gasthuis
City
Rotterdam
ZIP/Postal Code
3045 PM
Country
Netherlands
Facility Name
Moscow City Clinical Hospital # 62
City
Moscow
ZIP/Postal Code
125130
Country
Russian Federation
Facility Name
Hertzen Oncology Research Institute
City
Moscow
ZIP/Postal Code
125284
Country
Russian Federation
Facility Name
Clinical Oncology Dispensary
City
Omsk
ZIP/Postal Code
644013
Country
Russian Federation
Facility Name
Non-State Healthcare Institution 'Road Clinical Hospital of Russian Railways'
City
Saint Petersburg
ZIP/Postal Code
195271
Country
Russian Federation
Facility Name
Russian Scientific Center of Radiology and Surgical Technologies
City
Sankt-Peterburg
ZIP/Postal Code
197758
Country
Russian Federation
Facility Name
Hosp. Univ. Vall D Hebron
City
Barcelona
ZIP/Postal Code
8035
Country
Spain
Facility Name
Hosp. Gral. Univ. Gregorio Marañon
City
Madrid
ZIP/Postal Code
28009
Country
Spain
Facility Name
Hosp. Univ. Ramon Y Cajal
City
Madrid
ZIP/Postal Code
28034
Country
Spain
Facility Name
Hosp. Univ. Fund. Jimenez Diaz
City
Madrid
ZIP/Postal Code
28040
Country
Spain
Facility Name
Hosp. Univ. Hm Sanchinarro
City
Madrid
ZIP/Postal Code
28050
Country
Spain
Facility Name
Hosp. Virgen de La Victoria
City
Málaga
ZIP/Postal Code
29010
Country
Spain
Facility Name
Hosp. Quiron Madrid Pozuelo
City
Pozuelo de Alarcon
ZIP/Postal Code
28223
Country
Spain
Facility Name
Hosp. Univ. Marques de Valdecilla
City
Santander
ZIP/Postal Code
39008
Country
Spain
Facility Name
Instituto Valenciano de Oncologia
City
Valencia
ZIP/Postal Code
46009
Country
Spain

12. IPD Sharing Statement

Learn more about this trial

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

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