REGN21353 Alone or in Combination With Nezastomig for Metastatic Castration-Resistant Prostate Cancer in Adult Participants

Phase 1/2 Trial of REGN21353 (a STEAP1xCD3 Bispecific Antibody) Administered Alone or in Combination With Nezastomig (a PSMAxCD28 Bispecific Antibody) in Participants With Metastatic Castration-Resistant Prostate Cancer (mCRPC)

This study will test an experimental Regeneron drug called REGN21353 ("study drug") to see if it can help treat previously treated prostate cancer that has spread (also called metastatic castration-resistant prostate cancer or mCRPC). Some participants may get additional experimental drugs in combination with REGN21353. These additional drugs are nezastomig and sarilumab. "Experimental" means that the drugs are being tested and have not been approved for use in prostate cancer by a country's national health agency that gives approval for new medicines to be prescribed.

The study is looking at:

• What is the best dose of REGN21353 alone and together with nezastomig for treating prostate cancer
• What side effects REGN21353 alone and together with nezastomig might cause
• How well REGN21353 alone and together with nezastomig works
• How much REGN21353 alone and together with nezastomig is in the blood at different times
• If the body reacts to REGN21353 alone or together with nezastomig, in a way that may cause them to not work as well
• How REGN21353 alone and together with nezastomig could affect prostate cancer, which can help researchers understand why REGN21353 alone or together with nezastomig work better in some than others

Study Overview

• Status: Not yet recruiting
• Conditions: mCRPC; Metastatic Castration-Resistant Prostate Cancer
• Intervention / Treatment: Drug: REGN21353; Drug: Sarilumab Prophylaxis (Contingency); Drug: Nezastomig

• Study Type: Interventional
• Enrollment (Estimated): 192
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Clinical Trials Administrator; Phone Number: 844-734-6643; Email: clinicaltrials@regeneron.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Key Inclusion Criteria:

1. Is male with histologically or cytologically confirmed adenocarcinoma of the prostate without pure small cell carcinoma
2. Has metastatic castration-resistant prostate cancer with prostate-specific antigen value as described in the protocol and that has progressed within 6 months prior to screening
3. Has received ≥2 lines of prior systemic therapy approved in the metastatic and/or castration-resistant setting (in addition to androgen deprivation therapy) including at least one androgen receptor pathway inhibitor (eg, abiraterone, enzalutamide, apalutamide, or darolutamide)
4. Has had either orchiectomy or be on luteinizing hormone-releasing hormone (LHRH) agonist or antagonist therapy with serum testosterone levels as described in the protocol and agree to stay on LHRH agonist or antagonist therapy during the trial
5. Is able and willing to provide tumor tissue, either archival or newly obtained
6. Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
7. Has adequate organ, bone marrow, renal and hepatic function

Key Exclusion Criteria:

1. Has not recovered (ie, grade ≤1 or baseline) from immune-mediated adverse event within 3 months prior to initiation of trial intervention therapy except for endocrinopathies adequately managed with hormone replacement
2. Has permanently discontinued anti-cancer immune modulating therapies due to immune-mediated adverse events
3. Has another malignancy that is progressing or requires active treatment, except non-melanoma skin cancer that has undergone potentially curative therapy or any tumor that has been deemed to be effectively treated with definitive local control
4. Has ongoing or recent (within 5 years) evidence of significant autoimmune disease (including any history of systemic vasculitis) that required treatment with systemic immunosuppressive treatments
5. Has active liver metastases
6. Has current evidence of or history of central nervous system metastases as described in the protocol
7. Has encephalitis, meningitis, neurodegenerative disease (with the exception of mild dementia that does not interfere with activities of daily living), or uncontrolled seizures in the year prior to first dose of trial intervention
8. Has a known history of, or any evidence of, interstitial lung disease or active, noninfectious pneumonitis (past 5 years). A history of radiation pneumonitis in the radiation field is permitted
9. Has active or recent infection requiring hospitalization or treatment with intravenous anti-infectives within 2 weeks of first dose of trial intervention
10. Has significant cardiovascular disease

Note: Other protocol defined Inclusion/ Exclusion criteria apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Module 1: monotherapy	Drug: REGN21353; Administered per the protocol; Drug: Sarilumab Prophylaxis (Contingency); May be administered as pretreatment, per the protocol; Other Names: SAR153191; REGN88; KEVZARA®
Experimental: Module 2: combination	Drug: REGN21353; Administered per the protocol; Drug: Sarilumab Prophylaxis (Contingency); May be administered as pretreatment, per the protocol; Other Names: SAR153191; REGN88; KEVZARA®; Drug: Nezastomig; Administered per the protocol; Other Names: REGN5678

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Occurrence of Treatment Emergent Adverse Events (TEAEs)	Dose escalation	Up to 5 years
Occurrence of Dose-Limiting Toxicities (DLTs)	Dose escalation	Up to 42 days
Occurrence of Serious Adverse Events (SAEs)	Dose escalation	Up to 5 years
Occurrence of Adverse Events of Special Interests (AESIs)	Dose escalation	Up to 5 years
Composite Response Rate (CRR) of ≥50% decline of prostate specific antigen (PSA) and/or confirmed radiographic response of complete response (CR) or partial response (PR)	Dose expansion	Up to 5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
(CRR) of ≥50% decline of prostate specific antigen (PSA) and/or confirmed radiographic response of complete response (CR) or partial response (PR)	Dose escalation	Up to 5 years
Occurrence of TEAEs	Dose expansion	Up to 5 years
Occurrence of SAEs	Dose expansion	Up to 5 years
Occurrence of AESIs	Dose expansion	Up to 5 years
Percentage of participants with ≥50% reduction in PSA confirmed by a second PSA test ≥3 weeks later	Dose Escalation and Dose Expansion	Up to 5 years
Percentage of participants with ≥90% reduction in PSA confirmed by a second PSA test ≥3 weeks later	Dose Escalation and Dose Expansion	Up to 5 years
REGN21353 serum concentrations	Dose Escalation and Dose Expansion	Up to 5 years
Nezastomig serum concentrations	Dose Escalation and Dose Expansion	Up to 5 years
Occurrence of Anti-Drug Antibodies (ADA) to REGN21353	Dose Escalation and Dose Expansion	Up to 5 years
Occurrence of ADA to nezastomig	Dose Escalation and Dose Expansion	Up to 5 years
Magnitude of ADA to REGN21353	Dose Escalation and Dose Expansion	Up to 5 years
Magnitude of ADA to nezastomig	Dose Escalation and Dose Expansion	Up to 5 years

Collaborators and Investigators

• Sponsor: Regeneron Pharmaceuticals
• Investigators: Study Director: Clinical Trial Management, Regeneron Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Estimated): June 28, 2027
• Primary Completion (Estimated): July 28, 2031
• Study Completion (Estimated): July 28, 2031

Study Registration Dates

• First Submitted: September 23, 2026
• First Submitted That Met QC Criteria: September 23, 2026
• First Posted (Actual): September 30, 2026

Study Record Updates

• Last Update Posted (Actual): September 30, 2026
• Last Update Submitted That Met QC Criteria: September 23, 2026
• Last Verified: September 1, 2026

More Information

Terms related to this study

• Keywords: Metastatic prostate cancer; Prostate cancer; Luteinizing hormone-releasing hormone (LHRH); Hormone refractory prostate cancer; Advanced prostate cancer; Androgen deprivation therapy (ADT); Castration resistant prostate cancer; Androgen-independent prostate cancer; PSA progression; Stage 4 prostate cancer; Prostate cancer that has spread; Androgen-resistant prostate cancer; Androgen receptor pathway inhibitor (ARPI)
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Prostatic Diseases; Male Urogenital Diseases; Prostatic Neoplasms; sarilumab
• Other Study ID Numbers: R21353-ONC-25105

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

All Individual Patient Data (IPD) that underlie publicly available results will be considered for sharing

IPD Sharing Time Frame

When Regeneron has:

• received marketing authorization from major health authorities (e.g., FDA, European Medicines Agency (EMA), Pharmaceuticals and Medical Devices Agency (PMDA), etc.) for the product and indication or has globally discontinued development of the product for all indications on or after April 2020 and has no plans for future development
• made the study results publicly available (e.g., scientific publication, scientific conference, clinical trial registry)
• the legal authority to share the data, and
• ensured the ability to protect participant privacy

IPD Sharing Access Criteria

Qualified researchers can submit a proposal for access to individual patient or aggregate level data from a Regeneron-sponsored clinical trial through Vivli. Regeneron's Independent Research Request Evaluation Criteria can be found at: https://www.regeneron.com/sites/default/files/Regeneron-External-Data-Sharing-Policy-and-Independent-Research-Request-Evaluation-Criteria.pdf

• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No