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

NCT ID: NCT03551782

Last Updated: 2022-02-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 33 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-06-28
• Study Completion Date: 2021-11-11

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.

Conditions

Castration-Resistant Prostatic Neoplasms

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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).

Group Type: EXPERIMENTAL

Cetrelimab 480 mg

Intervention Type: DRUG

Cetrelimab 480 mg will be administered intravenously (IV) on Cycle 1 Day 1, then every 4 weeks thereafter (Q4W).

Apalutamide 240 mg

Intervention Type: DRUG

Apalutamide 240 mg (4\*60 mg) tablets per day will be administered orally.

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.

Group Type: EXPERIMENTAL

Cetrelimab 480 mg

Intervention Type: DRUG

Cetrelimab 480 mg will be administered intravenously (IV) on Cycle 1 Day 1, then every 4 weeks thereafter (Q4W).

Apalutamide 240 mg

Intervention Type: DRUG

Apalutamide 240 mg (4\*60 mg) tablets per day will be administered orally.

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).

Group Type: EXPERIMENTAL

Cetrelimab 480 mg

Intervention Type: DRUG

Cetrelimab 480 mg will be administered intravenously (IV) on Cycle 1 Day 1, then every 4 weeks thereafter (Q4W).

Apalutamide 240 mg

Intervention Type: DRUG

Apalutamide 240 mg (4\*60 mg) tablets per day will be administered orally.

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).

Group Type: EXPERIMENTAL

Cetrelimab 480 mg

Intervention Type: DRUG

Cetrelimab 480 mg will be administered intravenously (IV) on Cycle 1 Day 1, then every 4 weeks thereafter (Q4W).

Apalutamide 240 mg

Intervention Type: DRUG

Apalutamide 240 mg (4\*60 mg) tablets per day will be administered orally.

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).

Group Type: EXPERIMENTAL

Cetrelimab 480 mg

Intervention Type: DRUG

Cetrelimab 480 mg will be administered intravenously (IV) on Cycle 1 Day 1, then every 4 weeks thereafter (Q4W).

Apalutamide 240 mg

Intervention Type: DRUG

Apalutamide 240 mg (4\*60 mg) tablets per day will be administered orally.

Interventions

Cetrelimab 480 mg

Cetrelimab 480 mg will be administered intravenously (IV) on Cycle 1 Day 1, then every 4 weeks thereafter (Q4W).

Intervention Type: DRUG

Apalutamide 240 mg

Apalutamide 240 mg (4\*60 mg) tablets per day will be administered orally.

Intervention Type: DRUG

Other Intervention Names

JNJ-63723283; JNJ-56021927

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

Janssen Research & Development, LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Janssen Research & Development, LLC Clinical Trial

Role: STUDY_DIRECTOR

Janssen Research & Development, LLC

Locations

University of California San Francisco (UCSF) - Prostate Cancer Center

San Francisco, California, United States

Regional Urology LLC

Shreveport, Louisiana, United States

University of Michigan Health System

Ann Arbor, Michigan, United States

Washington University

Bay Saint Louis, Mississippi, United States

New York University Langone Medical Center

New York, New York, United States

Icahn School of Medicine at Mount Sinai - The Derald H. Ruttenberg

New York, New York, United States

Levine Cancer Institute, Carolinas HealthCare System

Charlotte, North Carolina, United States

Centers for Advanced Urology, LLC; d/b/a MidLantic Urology

Bala-Cynwyd, Pennsylvania, United States

Thomas Jefferson University

Philadelphia, Pennsylvania, United States

University of Texas, MD Anderson Cancer Center

Houston, Texas, United States

Virginia Oncology Associates

Norfolk, Virginia, United States

Grand Hôpital de Charleroi, site Notre Dame

Charleroi, , Belgium

AZ Maria Middelares

Ghent, , Belgium

Cross Cancer Institute

Edmonton, Alberta, Canada

University of Toronto

Toronto, Ontario, Canada

Centre de Recherche du CHUM

Montreal, Quebec, Canada

Istituto Europeo di Oncologia Servizio Radioterapia

Milan, , Italy

NKI-AVL, Amsterdam

Amsterdam, , Netherlands

UMC Radboud

Nijmegen, , Netherlands

Sint Franciscus Gasthuis

Rotterdam, , Netherlands

Moscow City Clinical Hospital # 62

Moscow, , Russia

Hertzen Oncology Research Institute

Moscow, , Russia

Clinical Oncology Dispensary

Omsk, , Russia

Non-State Healthcare Institution 'Road Clinical Hospital of Russian Railways'

Saint Petersburg, , Russia

Russian Scientific Center of Radiology and Surgical Technologies

Saint Petersburg, , Russia

Hosp. Univ. Vall D Hebron

Barcelona, , Spain

Hosp. Gral. Univ. Gregorio Marañon

Madrid, , Spain

Hosp. Univ. Ramon Y Cajal

Madrid, , Spain

Hosp. Univ. Fund. Jimenez Diaz

Madrid, , Spain

Hosp. Univ. Hm Sanchinarro

Madrid, , Spain

Hosp. Virgen de La Victoria

Málaga, , Spain

Hosp. Quiron Madrid Pozuelo

Pozuelo de Alarcón, , Spain

Hosp. Univ. Marques de Valdecilla

Santander, , Spain

Instituto Valenciano de Oncologia

Valencia, , Spain

Countries

United States; Belgium; Canada; Italy; Netherlands; Russia; Spain

Other Identifiers

2018-000182-37

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

56021927PCR2032

Identifier Type: OTHER

Identifier Source: secondary_id

CR108476

Identifier Type: -

Identifier Source: org_study_id