A Trial to Find Out if REGN5678 (Nezastomig) is Safe and How Well it Works Alone or in Combination With Cemiplimab for Adult Participants With Metastatic Castration-Resistant Prostate Cancer and Other Tumors

A Phase 1/2 Study of REGN5678 (Anti-PSMAxCD28) With or Without Cemiplimab (Anti-PD-1) in Patients With Metastatic Castration-Resistant Prostate Cancer and Other Tumors Associated With PSMA Expression

The main purpose of this study is to determine the safety, tolerability (how the body reacts to the drug[s]) and effectiveness (ability to treat the cancer) of REGN5678 (Nezastomig) alone, or in combination with cemiplimab.

The study has 2 parts. The goal of Part 1 (dose escalation) is to determine a safe dose(s) of REGN5678 when it is given alone or in combination with cemiplimab. The goal of Part 2 (dose expansion) is to use the REGN5678 drug dose(s) found in Part 1 to see how well REGN5678 alone or in combination with cemiplimab works to shrink tumors.

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

1. Side effects that may be experienced by taking REGN5678 alone or in combination with cemiplimab
2. How REGN5678 alone or in combination with cemiplimab works in the body
3. How much REGN5678 and/or cemiplimab are present in the blood
4. To see if REGN5678 alone or in combination with cemiplimab works to reduce the size of the tumor by helping the immune system destroy the tumor

Study Overview

• Status: Recruiting
• Conditions: Metastatic Castration-Resistant Prostate Cancer (mCRPC); Clear Cell Renal Cell Carcinoma (ccRCC)
• Intervention / Treatment: Drug: REGN5678; Drug: Cemiplimab

• Study Type: Interventional
• Enrollment (Estimated): 345
• 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
  • Arizona
    • Gilbert, Arizona, United States, 85234
      • Recruiting
      • Banner MD Anderson Cancer Center
    • Phoenix, Arizona, United States, 85054
      • Recruiting
      • Mayo Clinic
    • Tucson, Arizona, United States, 85724
      • Recruiting
      • University of Arizona
  • California
    • Santa Monica, California, United States, 90404
      • Recruiting
      • John Wayne Cancer Institute (JWCI)
  • Colorado
    • Denver, Colorado, United States, 80218
      • Recruiting
      • Sarah Cannon Research Institute (SCRI)
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Recruiting
      • Yale University Hospital
  • Florida
    • Jacksonville, Florida, United States, 32224
      • Recruiting
      • Mayo Clinic Jacksonville
    • Tampa, Florida, United States, 33612
      • Recruiting
      • Moffitt Cancer Center - McKinley Drive
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Recruiting
      • Massachusetts General Hospital
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Recruiting
      • Mayo Clinic
  • New York
    • New York, New York, United States, 10029
      • Recruiting
      • Icahn School of Medicine at Mount Sinai
    • New York, New York, United States, 10461
      • Recruiting
      • Montefiore Medical Center
    • New York, New York, United States, 10016
      • Recruiting
      • NYU Langone Health Perlmutter Cancer Center
    • New York, New York, United States, 10032
      • Recruiting
      • Columbia University - The Trustees of Columbia University in the City of New York
    • Rochester, New York, United States, 14642
      • Recruiting
      • University of Rochester Medical Center (URMC) - Wilmot Cancer Institute (WCI) (James P. Wilmot Cancer Center) - Rochester
  • Oregon
    • Portland, Oregon, United States, 97213
      • Withdrawn
      • Providence Portland Medical Center
    • Portland, Oregon, United States, 97239
      • Recruiting
      • Oregon Health & Science University (3485 S. Bond)
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Recruiting
      • Thomas Jefferson University Hospital
  • Rhode Island
    • Providence, Rhode Island, United States, 02903
      • Recruiting
      • Lifespan Cancer Institute
  • Texas
    • Houston, Texas, United States, 77030
      • Recruiting
      • MD Anderson Cancer Center
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • Recruiting
      • Emily Couric Clinical Cancer Center

Participation Criteria

Eligibility Criteria

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

Description

Key Inclusion Criteria:

mCRPC cohorts (men):

1. Men with histologically or cytologically confirmed adenocarcinoma of the prostate without pure small cell carcinoma.
2. PSA value at screening ≥4 ng/mL that has progressed within 6 months prior to screening as defined in the protocol.

3. Has received ≥2 lines prior systemic therapy approved in the metastatic and/or castration-resistant setting (in addition to Androgen Deprivation Therapy [ADT]) including at least:

   1. one second-generation anti-androgen therapy (eg, abiraterone, enzalutamide, apalutamide, or darolutamide)
   2. 177Lu-PSMA-617 radiotherapy, or another lutetium-based PSMA targeted radioligand, as described in the protocol

ccRCC cohorts (men and women):

1. Histologically or cytologically confirmed RCC with a clear-cell component.
2. Diagnosis of metastatic ccRCC with at least one measurable lesion via RECIST 1.1 criteria
3. Has progressed on or after ≥1 line prior systemic therapy approved in the metastatic setting. Prior treatment must include an anti-Programmed Death-1 (receptor) [PD-1]/Programmed Death-Ligand 1 (PD-L1) therapy and either ipilimumab and/or a tyrosine kinase inhibitor

Key Exclusion Criteria:

1. Has received treatment with an approved systemic therapy within 3 weeks of dosing or has not yet recovered (ie, grade ≤1 or baseline) from any acute toxicities, as described in the protocol
2. Has received any previous systemic biologic therapy within 5 half-lives of first dose of study therapy, as described in the protocol
3. Has received prior PSMA-targeting therapy with the exception of a PSMA targeting radioligand (eg. 177Lu-PSMA-617) in mCRPC
4. Dose Escalation: Has had prior anti-cancer immunotherapy (other than sipuleucel-T) within 5 half-lives prior to study therapy.
5. Dose Expansion (mCRPC only): Has had prior anti-cancer immunotherapy, as described in the protocol
6. 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
7. Ongoing or recent (within 5 years) evidence of significant autoimmune disease that required treatment with systemic immunosuppressive treatments, as described in the protocol
8. 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
9. Uncontrolled infection with Human Immunodeficiency Virus (HIV), hepatitis B or hepatitis C infection; or diagnosis of immunodeficiency

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

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: mCRPC - dose escalation cohort; REGN5678 with or without cemiplimab	Drug: REGN5678; Administered as per the protocol; Other Names: Nezastomig; Drug: Cemiplimab; Administered as per the protocol; Other Names: REGN2810; LIBTAYO
Experimental: mCRPC - dose expansion cohort; REGN5678 with or without cemiplimab	Drug: REGN5678; Administered as per the protocol; Other Names: Nezastomig
Experimental: ccRCC - dose escalation cohort; REGN5678 with or without cemiplimab	Drug: REGN5678; Administered as per the protocol; Other Names: Nezastomig; Drug: Cemiplimab; Administered as per the protocol; Other Names: REGN2810; LIBTAYO
Experimental: ccRCC - dose expansion cohort; REGN5678 with or without cemiplimab	Drug: REGN5678; Administered as per the protocol; Other Names: Nezastomig

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence and severity of Treatment-Emergent Adverse Events (TEAEs)	Dose Escalation Phase	Through study completion, up to 5 years
Incidence and severity of Adverse Event of Special Interests (AESIs)	Dose Escalation Phase	Through study completion, up to 5 years
Incidence and severity of Serious Adverse Events (SAEs)	Dose Escalation Phase	Through study completion, up to 5 years
Number of participants with Grade ≥3 laboratory abnormalities	Dose Escalation Phase	Through study completion, up to 5 years
Incidence of Dose-Limiting Toxicities (DLTs)	Dose Escalation Phase	First dose through day 42 of last participant in each dose level
Concentration of REGN5678 in serum over time	Dose Escalation Phase	Through study completion, up to 5 years
Concentration of REGN5678 in combination with cemiplimab in serum over time	Dose Escalation Phase	Through study completion, up to 5 years
Composite Response Rate (CRR) of 50% decline of Prostate Specific Antigen (PSA) and/or confirmed radiographic response of complete (CR) or partial response (PR)	Dose Expansion Phase - mCRPC cohort	Through study completion, up to 5 years
Objective Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria	Dose Expansion Phase - ccRCC cohort	Through study completion, up to 5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
CRR of 50% decline of PSA and/or confirmed radiographic of CR or PR	Dose Escalation Phase - mCRPC cohort	Through study completion, up to 5 years
ORR per RECIST 1.1 criteria	Dose Escalation Phase - ccRCC cohort	Through study completion, up to 5 years
Incidence and severity of TEAEs	Dose Expansion Phase	Through study completion, up to 5 years
Incidence and severity of AESIs	Dose Expansion Phase	Through study completion, up to 5 years
Incidence and severity of SAEs	Dose Expansion Phase	Through study completion, up to 5 years
Number of participants with grade ≥3 laboratory abnormalities	Dose Expansion Phase	Through study completion, up to 5 years
Concentration of REGN5678 in serum over time	Dose Expansion Phase	Through study completion, up to 5 years
Concentration of REGN5678 in combination with cemiplimab in serum over time	Dose Expansion Phase	Through study completion, up to 5 years
Percentage of participants with ≥50% decline of PSA	Dose Escalation and Dose Expansion Phases - mCRPC cohorts	Through study completion, up to 5 years
Percentage of participants with ≥90% decline of PSA	Dose Escalation and Dose Expansion Phases- mCRPC cohorts	Through study completion, up to 5 years
Presence or absence of antibodies against REGN5678	Dose Escalation and Dose Expansion Phases	Through study completion, up to 5 years
Presence or absence of antibodies against cemiplimab	Dose Escalation and Dose Expansion Phases	Through study completion, up to 5 years

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): August 12, 2019
• Primary Completion (Estimated): November 15, 2027
• Study Completion (Estimated): November 15, 2027

Study Registration Dates

• First Submitted: May 30, 2019
• First Submitted That Met QC Criteria: May 30, 2019
• First Posted (Actual): June 3, 2019

Study Record Updates

• Last Update Posted (Estimated): November 6, 2025
• Last Update Submitted That Met QC Criteria: November 5, 2025
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Urologic Neoplasms; Carcinoma; Kidney Neoplasms; Carcinoma, Renal Cell; Antineoplastic Agents, Immunological; Antineoplastic Agents; cemiplimab
• Other Study ID Numbers: R5678-ONC-1879; 2022-502131-19-00 (Other Identifier: 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