Clinical trial NCT03551782: 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: Castration-Resistant Prostatic Neoplasms
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2018-06-11
Enrollment: 33
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Number of Participants With Adverse Events (AEs)
timeFrame: Approximately 2 years
measure: Number of Participants with AEs by Severity
timeFrame: Approximately 2 years
measure: Percentage of Participants with Prostate-Specific Antigen (PSA) Response at Week 12
timeFrame: Week 12
Secondary outcomes:
measure: Maximal PSA Decline
timeFrame: Approximately 2 years
measure: Percentage of Participants with Circulating Tumor Cell (CTC) Response
timeFrame: Approximately 2 years
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: University of California San Francisco (UCSF) - Prostate Cancer Center
state: California
city: Shreveport
country: United States
facility: Regional Urology LLC
state: Louisiana
city: Ann Arbor
country: United States
facility: University of Michigan Health System
state: Michigan
city: Bay Saint Louis
country: United States
facility: Washington University
state: Mississippi
city: New York
country: United States
facility: New York University Langone Medical Center
state: New York
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai - The Derald H. Ruttenberg
state: New York
city: Charlotte
country: United States
facility: Levine Cancer Institute, Carolinas HealthCare System
state: North Carolina
city: Bala-Cynwyd
country: United States
facility: Centers for Advanced Urology, LLC; d/b/a MidLantic Urology
state: Pennsylvania
city: Philadelphia
country: United States
facility: Thomas Jefferson University
state: Pennsylvania
city: Houston
country: United States
facility: University of Texas, MD Anderson Cancer Center
state: Texas
city: Norfolk
country: United States
facility: Virginia Oncology Associates
state: Virginia
city: Charleroi
country: Belgium
facility: Grand Hôpital de Charleroi, site Notre Dame
city: Gent
country: Belgium
facility: AZ Maria Middelares
city: Edmonton
country: Canada
facility: Cross Cancer Institute
state: Alberta
city: Toronto
country: Canada
facility: University of Toronto
state: Ontario
city: Montreal
country: Canada
facility: Centre de Recherche du CHUM
state: Quebec
city: Milano
country: Italy
facility: Istituto Europeo di Oncologia Servizio Radioterapia
city: Amsterdam
country: Netherlands
facility: NKI-AVL, Amsterdam
city: Nijmegen
country: Netherlands
facility: UMC Radboud
city: Rotterdam
country: Netherlands
facility: Sint Franciscus Gasthuis
city: Moscow
country: Russian Federation
facility: Moscow City Clinical Hospital # 62
city: Moscow
country: Russian Federation
facility: Hertzen Oncology Research Institute
city: Omsk
country: Russian Federation
facility: Clinical Oncology Dispensary
city: Saint Petersburg
country: Russian Federation
facility: Non-State Healthcare Institution 'Road Clinical Hospital of Russian Railways'
city: Sankt-Peterburg
country: Russian Federation
facility: Russian Scientific Center of Radiology and Surgical Technologies
city: Barcelona
country: Spain
facility: Hosp. Univ. Vall D Hebron
city: Madrid
country: Spain
facility: Hosp. Gral. Univ. Gregorio Marañon
city: Madrid
country: Spain
facility: Hosp. Univ. Ramon Y Cajal
city: Madrid
country: Spain
facility: Hosp. Univ. Fund. Jimenez Diaz
city: Madrid
country: Spain
facility: Hosp. Univ. Hm Sanchinarro
city: Málaga
country: Spain
facility: Hosp. Virgen de La Victoria
city: Pozuelo de Alarcon
country: Spain
facility: Hosp. Quiron Madrid Pozuelo
city: Santander
country: Spain
facility: Hosp. Univ. Marques de Valdecilla
city: Valencia
country: Spain
facility: Instituto Valenciano de Oncologia
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References: