Description:
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.
Title
- 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
Clinical Trial IDs
- ORG STUDY ID:
CR108476
- SECONDARY ID:
2018-000182-37
- SECONDARY ID:
56021927PCR2032
- NCT ID:
NCT03551782
Conditions
- Castration-Resistant Prostatic Neoplasms
Interventions
Drug | Synonyms | Arms |
---|
Cetrelimab 480 mg | JNJ-63723283 | Cohort 1 |
Apalutamide 240 mg | JNJ-56021927 | Cohort 1 |
Purpose
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.
Trial Arms
Name | Type | Description | Interventions |
---|
Cohort 1 | Experimental | 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). | - Cetrelimab 480 mg
- Apalutamide 240 mg
|
Cohort 2 | Experimental | 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. | - Cetrelimab 480 mg
- Apalutamide 240 mg
|
Cohort 3 | Experimental | 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). | - Cetrelimab 480 mg
- Apalutamide 240 mg
|
Cohort 4 | Experimental | 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). | - Cetrelimab 480 mg
- Apalutamide 240 mg
|
Cohort 5 | Experimental | 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). | - Cetrelimab 480 mg
- Apalutamide 240 mg
|
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
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | Male |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Number of Participants With Adverse Events (AEs) |
Time Frame: | Approximately 2 years |
Safety Issue: | |
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. |
Secondary Outcome Measures
Measure: | Maximal PSA Decline |
Time Frame: | Approximately 2 years |
Safety Issue: | |
Description: | Maximal PSA decline is defined as maximal percent decrease in PSA at any time during treatment. |
Measure: | Percentage of Participants with Circulating Tumor Cell (CTC) Response |
Time Frame: | Approximately 2 years |
Safety Issue: | |
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. |
Details
Phase: | Phase 1 |
Primary Purpose: | Interventional |
Overall Status: | Active, not recruiting |
Lead Sponsor: | Janssen Research & Development, LLC |
Last Updated
May 24, 2021