A Trial to Find Out if REGN4336 is Safe and How Well it Works Alone and in Combination With REGN5678 for Adult Participants With Advanced Prostate Cancer

Phase 1/2 Study of REGN4336 (a PSMAxCD3 Bispecific Antibody) Administered Alone or in Combination With REGN5678 (a PSMAxCD28 Bispecific Antibody) in Patients With Metastatic Castration-Resistant Prostate Cancer

This study is researching an investigational drug called REGN4336 both alone or together with another investigational drug called REGN5678. The study is focused on participants with previously treated metastatic prostate cancer.

The main purpose of the study is to look at the safety, tolerability (how the body reacts to the drug) and effectiveness (how well the drug works to shrink tumors) of REGN4336 when given in combination with REGN5678.

The study has 2 parts. The purpose of Part 1 is to determine a safe dose(s) of REGN4336 to be given alone or in combination with REGN5678. Part 1 is known as the "dose escalation" phase.

The purpose of Part 2, (known as the "dose expansion" phase), is to use the doses of REGN4336 and REGN5678 selected in Part 1 to further test how well the combination treatment with REGN4336 and REGN5678 works to shrink tumors.

The study is looking at several other research questions, including:

• What side effects may happen from taking REGN4336 alone or in combination with REGN5678
• How well does REGN4336 in combination with REGN5678 reduce tumor size
• How much REGN4336 is in the blood at different times when it is given alone or in combination with REGN5678
• Does the body make antibodies against the study drugs (REGN4336 or REGN5678)

Study Overview

• Status: Recruiting
• Conditions: Metastatic Castration-resistant Prostate Cancer
• Intervention / Treatment: Drug: REGN4336; Drug: REGN5678

• Study Type: Interventional
• Enrollment (Estimated): 228
• Phase: Phase 2; Phase 1

Contacts and Locations

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

Study Locations

• United States
  • California
    • Palo Alto, California, United States, 94304
      • Recruiting
      • Stanford University Medical Center - Blake Wilbur Drive
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Recruiting
      • Yale University Hospital
  • Kentucky
    • Louisville, Kentucky, United States, 40207
      • Recruiting
      • Norton Cancer Institute
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • Recruiting
      • University of Maryland Greenebaum Cancer Center
  • New Jersey
    • New Brunswick, New Jersey, United States, 08901
      • Recruiting
      • Rutgers Cancer Institute of New Jersey
  • New York
    • Buffalo, New York, United States, 14263
      • Recruiting
      • Roswell Park Cancer Institute
  • North Carolina
    • Charlotte, North Carolina, United States, 28204
      • Recruiting
      • Atrium Health Levine Cancer Institute
  • Ohio
    • Columbus, Ohio, United States, 43210
      • Recruiting
      • The Ohio State University James Cancer Hospital
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Recruiting
      • Thomas Jefferson University Hospital
    • Philadelphia, Pennsylvania, United States, 19111
      • Recruiting
      • Fox Chase Cancer Center
    • Philadelphia, Pennsylvania, United States, 19111
      • Withdrawn
      • Fox Chase Cancer Center
    • Philadelphia, Pennsylvania, United States, 19104
      • Recruiting
      • Penn Medicine University of Pennsylvania Health System
  • Texas
    • Houston, Texas, United States, 77030
      • Recruiting
      • MD Anderson Cancer Center
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Recruiting
      • Medical College of Wisconsin

Participation Criteria

Eligibility Criteria

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

Description

Key Inclusion Criteria:

1. Histologically or cytologically confirmed adenocarcinoma of the prostate without pure small cell carcinoma

2. Metastatic, Castration-Resistant Prostate Cancer (mCRPC) with PSA value at screening ≥4 ng/mL and that has progressed within 6 months prior to screening, according to at least 1 of the following:

   1. PSA progression as defined by a rising PSA level confirmed with an interval of ≥1 week between each assessment
   2. Radiographic disease progression in soft tissue based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 criteria with or without PSA progression
   3. Radiographic disease progression in bone defined as the appearance of 2 or more new bone lesions on bone scan with or without PSA progression NOTE: Measurable disease per RECIST version 1.1 per local reading at screening is not an eligibility criterion for enrollment
3. Has progressed upon or intolerant to ≥2 lines prior systemic therapy approved in the metastatic and/or castration-resistant setting (in addition to Androgen Deprivation Therapy [ADT]) including at least one second-generation anti-androgen therapy (e.g. abiraterone, enzalutamide, apalutamide, or darolutamide)

Key Exclusion Criteria:

1. Has received treatment with an approved systemic biologic therapy within 3 weeks of dosing or has not yet recovered (ie, grade ≤1 or baseline) from any acute toxicities except for laboratory changes as described in inclusion criteria
2. Has received any previous systemic biologic or anti-cancer immunotherapy within 5 half-lives of first dose of study therapy, as described in the protocol
3. Has received prior Prostate-Specific Membrane Antigen (PSMA)-targeting therapy NOTE: Prior therapy with PSMA-targeting radioligand(s) (eg, 177Lu-PSMA-617) is permitted. However, a period of 12 weeks must elapse between the last dose of the PSMA- targeting radioligand and the first dose of study drug
4. Any condition that requires ongoing/continuous corticosteroid therapy (>10 mg prednisone/day or anti-inflammatory equivalent) within 1 week prior to the first dose of study therapy
5. Ongoing or recent (within 5 years) evidence of significant autoimmune disease that required treatment with systemic immunosuppressive treatments
6. Encephalitis, meningitis, neurodegenerative disease (with the exception of mild dementia that does not interfere with Activities of Daily Living [ADLs]) or uncontrolled seizures in the year prior to first dose of study therapy
7. Uncontrolled infection with Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV), or Hepatitis C Virus (HCV) infection; or diagnosis of immunodeficiency, as described in the protocol.

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: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Module 1- Monotherapy	Drug: REGN4336; Administered per the protocol
Experimental: Module 3-Combo Therapy	Drug: REGN4336; Administered per the protocol; Drug: REGN5678; Administered per the protocol

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence and severity of Serious Adverse Events (SAEs)	Dose escalation	Up to 5 years
REGN4336 monotherapy concentrations in serum	Dose escalation	Up to 5 years
REGN4336 concentrations in serum in combination with REGN5678	Dose escalation	Up to 5 years
Incidence of Dose-Limiting Toxicities (DLTs)	Dose escalation	up to 21 days
Incidence and severity of Treatment-Emergent Adverse Events (TEAEs)	Dose escalation	Up to 5 years
Incidence and severity of Adverse Events of Special Interest (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
Incidence and severity of TEAEs	Dose expansion	Up to 5 years
Incidence and severity of SAEs	Dose expansion	Up to 5 years
Incidence and severity of AESIs	Dose expansion	Up to 5 years
REGN4336 concentrations in serum in combination with REGN5678	Dose expansion	Up to 5 years
CRR of ≥50% decline of PSA and/or confirmed radiographic response of CR or PR	Dose escalation	Up to 5 years
Anti-Drug Antibodies (ADA) to REGN4336	Dose escalation	Up to 5 years
ADA to REGN4336 and REGN5678	Dose escalation and dose expansion	Up to 5 years
Percentage of patients 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 patients with ≥90% reduction in PSA confirmed by a second PSA test ≥3 weeks later	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 (Actual): November 30, 2021
• Primary Completion (Estimated): March 28, 2030
• Study Completion (Estimated): March 28, 2030

Study Registration Dates

• First Submitted: October 25, 2021
• First Submitted That Met QC Criteria: November 10, 2021
• First Posted (Actual): November 18, 2021

Study Record Updates

• Last Update Posted (Actual): May 5, 2026
• Last Update Submitted That Met QC Criteria: April 30, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Treatment-experienced metastatic Castration-Resistant Prostate Cancer (mCRPC)
• 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; Antineoplastic Agents, Immunological; Antineoplastic Agents; cemiplimab; sarilumab
• Other Study ID Numbers: R4336-ONC-20104; 2022-502130-17-00 (Ctis: EUCT Number)

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