Apalutamide Plus Cetrelimab in Patients With Treatment-Emergent Small Cell Neuroendocrine Prostate Cancer

NCT04926181 | Terminated Phase 2 Results DMC FDA Drug

• 2 other identifiers: 21553NCI-2021-05986
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

Brief Summary

Despite the low androgen receptor (AR) transcriptional activity of treatment-emergent small cell neuroendocrine prostate cancer, there is persistent AR expression observed in the majority of treatment-emergent small-cell neuroendocrine prostate cancer (t-SCNC) biopsies. This indicates that epigenetic dysregulation leads to reprogramming away from an AR-driven transcriptional program. Therefore, continuation of AR blockade in the form of apalutamide may provide additive benefit compared to immune checkpoint blockade alone. The investigators hypothesize that the combination of apalutamide plus cetrelimab will achieve a clinically significant composite response rate with sufficient durability of response in mCRPC patients with evidence of treatment-emergent small cell neuroendocrine prostate cancer

Conditions

Small Cell Neuroendocrine Carcinoma; Prostate Cancer; Small Cell Carcinoma

Keywords

Immunotherapy; Androgen receptor

Outcome Measures

Primary Outcomes (1)

• Composite Response Rate

  The composite response rate is determined by a combination of a decline from baseline in serum PSA of \>= 50%, confirmed by repeat measurement ≥ 4 weeks later (PSA50) AND a complete response (CR) or partial response (PR) as determined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 criteria confirmed by repeat scan ≥ 4 weeks later.

  Up to 2 years

Secondary Outcomes (8)

• Proportion of Participants With Treatment-related Adverse Events (AEs)

  Up to 2 years

• Median Radiographic Progression-free Survival (PFS)

  Up to 2 years

• Proportion of Participants With a >=50% Decline in PSA

  Up to 2 years

• Proportion of Participants With a >=90% Decline in PSA

  Up to 2 years

• Median PSA Progression-free Survival (PFS)

  Up to 2 years

Study Arms (1)

Single Arm: Apalutamide + Cetrelimab

EXPERIMENTAL

Participants will be given Apalutamide tablets combined with infusions of Cetrelimab in 28-day cycles, for up maximum of two years.

Drug: Apalutamide; Biological: Cetrelimab

Interventions

Apalutamide DRUG

240 mg once daily, for a 28 day cycle

Also known as: Erleada, Androgen Receptor Inhibitorsv(ARI), Apalutamide Oral Tablet

Single Arm: Apalutamide + Cetrelimab

Cetrelimab BIOLOGICAL

480 mg given through intravenous infusion (IV) on day 1 of every 28-day treatment cycle and administered over a 60-minute infusion

Also known as: JNJ-63723283, Anti-PD-1 antibody cetrelimab (JNJ-63723283), CET

Single Arm: Apalutamide + Cetrelimab

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants must have histologically confirmed prostate adenocarcinoma at the time of diagnosis, with subsequent development of metastatic castration-resistant prostate cancer. Prostate adenocarcinoma with neuroendocrine features (e.g. positive chromogranin and/or synaptophysin expression by IHC) is allowed.
• Evidence of disease progression (PD) by PSA and/or radiographic progression by Prostate Cancer Clinical Trials Working Group 3 (PCWG3) criteria at the time of study entry.
• Prior progression on at least one androgen signaling inhibitor (e.g. abiraterone acetate, apalutamide, enzalutamide, darolutamide ). Treatment with prior androgen signaling inhibitor may have been initiated in either the castration-sensitive prostate cancer (CSPC) and/or CRPC setting.
• Patients must be evaluable for the primary endpoint of composite response and must have either serum Prostate-specific antigen (PSA) \> 2 ng/mL during screening and/or measurable disease by RECIST 1.1 criteria.
• Participants must have clinicogenomic evidence of treatment emergent small cell neuroendocrine prostate cancer as defined by one or more of the following:
• Histologic evidence of small cell neuroendocrine prostate cancer on evaluation of castrate resistant prostate cancer (CRPC) tissue by centralized pathology review and/or
• Presence of loss-of-function mutation or deletion of Retinoblastoma (RB1) gene on a Clinical Laboratory Improvement Amendments (CLIA)-approved genomic-sequencing platform. Either monoallelic or biallelic mutations in RB1 are allowed.
• No more than one prior line of taxane-based chemotherapy administered in the metastatic castrate resistant prostate cancer (mCRPC) setting. Chemotherapy administered in the castration-sensitive setting does not count towards this limit. Prior carboplatin is allowed and does not count as an additional line of therapy when given in conjunction with taxane.
• Castrate level of serum testosterone at study entry (\<50 ng/dL). Patients without prior bilateral orchiectomy are required to remain on Luteinizing hormone-releasing hormone (LHRH) analogue treatment for duration of study.
• No other systemic anti-cancer therapies administered other than LHRH analogue within 14 days or, 5 half-lives, whichever is shorter, prior to initiation of study treatment. Adverse Events (AEs) related to prior anti-cancer treatment must have recovered to Grade \<= 1 with the exception of any grade alopecia and Grade \<= 2 neuropathy.
• a. Patients receiving apalutamide prior to study entry may continue treatment at their current apalutamide dose level without requirement for wash-out period.
• Age \>= 18 years
• Eastern Cooperative Oncology Group (ECOG) performance status \<= 1 (Karnofsky performance status \>= 70%)
• Demonstrates adequate organ function as defined below:
• Absolute neutrophil count \>= 1,500/microliter (mcL)

You may not qualify if:

• De novo small cell carcinoma of the prostate.
• Has participated in a study of an investigational product and received study treatment or used an investigational device other than those specified in the protocol within 2 weeks of C1D1.
• Hypersensitivity to cetrelimab, apalutamide, or any of its excipients.
• Has received prior radiotherapy within 2 weeks of C1D1. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (\<=2 weeks of radiotherapy) to non-central nervous system (CNS) disease.
• Receipt of prior cetrelimab or another immune checkpoint inhibitor targeting PD-1/PD-L1 and/or cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) (e.g. pembrolizumab, nivolumab, ipilimumab). Prior treatment with sipuleucel-T is allowed.
• Has an active autoimmune disease that has required systemic treatment in the past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Patients on low dose oral weekly methotrexate are allowed. Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) or treatment with drugs (e.g. methimazole, neomercazole, carbimazole, etc.) that function to decrease the generation of thyroid hormone by a hyper-functioning thyroid gland (e.g., in Graves' disease) is not considered a form of systemic treatment of an autoimmune disease.
• Has received a live vaccine within 30 days prior to the first dose of study drug. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g., FluMist®) are live attenuated vaccines and are not allowed. Coronavirus-2019 (COVID-19) vaccine is allowed.
• Individuals with concurrent second malignancy requiring active treatment at study entry that could affect safety or efficacy endpoints. Non-melanoma skin cancer, non-muscle invasive bladder cancer, and other carcinomas-in-situ are allowable exceptions.
• Cardiac condition as defined as one or more of the following:
• Uncontrolled supraventricular arrhythmia or ventricular arrhythmia requiring treatment
• New York Heart Association (NYHA) congestive heart failure class III or IV
• History of unstable angina, myocardial infarction, or cerebrovascular accident within 6 months prior to C1D1
• Uncontrolled hypertension defined as systolic BP (SBP) \>= 160 mm Hg and/or diastolic BP (DBP) \>= 100 mmHg. Treatment and re-screening are permitted.
• History of seizure or pre-disposing condition (e.g. brain metastases). Medications known to lower seizure threshold must be discontinued at least 4 weeks prior to C1D1.
• Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy at a prednisone equivalent dose of \> 10 mg daily or other form of immunosuppressive therapy within 7 days prior to first dose of study drug.

Sponsors & Collaborators

• Rahul Aggarwal: lead
• Janssen Scientific Affairs, LLC: collaborator

Study Sites (1)

University of California, San Francisco

San Francisco, California, 94143, United States

Location

MeSH Terms

Conditions

Small Cell Lung Carcinoma; Prostatic Neoplasms; Carcinoma, Small Cell; Bulbo-Spinal Atrophy, X-Linked

Interventions

apalutamide

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Genital Neoplasms, Male; Urogenital Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Muscular Atrophy, Spinal; Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Motor Neuron Disease; Neuromuscular Diseases; Genetic Diseases, X-Linked; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Limitations and Caveats

Study was terminated and closed earlier than expected due to lack of funding. The timing of study closure and patient-related events prevented the collection of confirmatory response data needed for objective response determination.

Results Point of Contact

• Title: Dr. Rahul Aggarwal, MD
• Organization: University of California, San Francisco

Rahul.Aggarwal@ucsf.edu

(415) 476-1000

Study Officials

• Rahul Aggarwal, MD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: June 8, 2021
• First Posted: June 15, 2021
• Study Start: March 16, 2022
• Primary Completion: March 31, 2024
• Study Completion: March 31, 2024
• Last Updated: May 15, 2025
• Results First Posted: May 15, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)