REGN15505 (PSMAx4-1BB) Alone or in Combination With Cemiplimab or REGN4336 (PSMAxCD3) in Adult Patients With Metastatic Castration-Resistant Prostate Cancer and Clear Cell Renal Cell Carcinoma

Phase 1/2 Study of REGN15505 (a PSMAx4-1BB Bispecific Antibody) Administered Alone or in Combination With Cemiplimab or REGN4336 (a PSMAxCD3 Bispecific Antibody) in Patients With Metastatic Castration-Resistant Prostate Cancer and Clear Cell Renal Cell Carcinoma

This study is researching a new drug called REGN15505 when used alone or in combination with cemiplimab or in combination with REGN4336 in adult patients with mCRPC and ccRCC. The goal is to explore new ways to treat these cancers by helping immune cells target and destroy cancer cells.

The study will evaluate the use of REGN15505 when administered alone, in combination with cemiplimab, or in combination with REGN4336 for:

• Any side effects of study drugs
• How well the study drugs work
• How much REGN15505, cemiplimab, and REGN4336 are in the blood at different times
• If the body makes antibodies to REGN15505 or REGN4336, which may mean the study drugs will not work as well as expected
• What is the best dose of REGN15505 when administered alone and with cemiplimab and the best dose of REGN15505 and REGN4336 when used in combination

Study Overview

• Status: Not yet recruiting
• Conditions: Metastatic Castration-Resistant Prostate Cancer (mCRPC); Clear Cell Renal Cell Carcinoma (ccRCC)
• Intervention / Treatment: Drug: REGN15505; Drug: REGN15505+Cemiplimab; Drug: REGN15505+REGN4336

• Study Type: Interventional
• Enrollment (Estimated): 265
• 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: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

Participants with mCRPC:

1. Men with histologically or cytologically confirmed adenocarcinoma of the prostate without pure small cell carcinoma
2. mCRPC with PSA value at screening ≥4 ng/mL and that has progressed within 6 months prior to screening as described in the protocol
3. Has received ≥2 lines of prior systemic therapy approved in the metastatic and/or castration-resistant setting as described in the protocol

4. Have had either Orchiectomy or be on Luteinizing Hormone-Releasing Hormone (LHRH) agonist or antagonist therapy with serum testosterone <50 ng/dL AND agree to stay on LHRH agonist or antagonist therapy during the study

   Participants with ccRCC:

5. Men and women with histologically or cytologically confirmed Renal Cell Carcinoma (RCC) with a clear-cell component
6. Diagnosis of metastatic ccRCC with at least 1 measurable lesion via Response evaluation criteria in solid tumors (RECIST) 1.1 criteria
7. Has progressed on or after ≥1 line of prior systemic therapy approved in the metastatic setting. Prior treatment must include an Anti Program Cell Death 1 (PD-1)/ Program Death Ligand 1 (PD-L1) therapy and either ipilimumab and/or a Tyrosine Kinase Inhibitor (TKI)

Key Exclusion Criteria:

For Both mCRPC and ccRCC Cohorts:

1. Has received treatment with an approved systemic therapy (including sipuleucel-T for mCRPC patients) 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 the protocol

   mCRPC Cohort Only:

2. Has received prior Prostate Specific Membrane Antigen (PSMA)-targeting therapy with the exception of a PSMA-targeting radioligand (eg, 177Lu-PSMA-617)

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

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Module 1: Monotherapy; REGN15505	Drug: REGN15505; Administered per protocol
Experimental: Module 2: Combination 1; REGN15505 and Cemiplimab	Drug: REGN15505+Cemiplimab; Administered per protocol; Other Names: REGN2810; Libtayo
Experimental: Module 3: Combination 2; REGN15505 and REGN4336	Drug: REGN15505+REGN4336; Administered per protocol

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Occurrence of Dose Limiting Toxicities (DLTs)	Dose Escalation	Up to 5 years
Occurrence of Treatment-Emergent Adverse Events (TEAEs)	Dose Escalation	Up to 5 years
Occurrence of Serious Adverse Events (SAEs)	Dose Escalation	Up to 5 years
Occurrence of Adverse Events of Special Interest (AESIs)	Dose Escalation	Up to 5 years
Composite Response (CompR) based on ≥50% decline of Prostate Specific Antigen (PSA) and/or confirmed radiographic assessment of complete response (CR) or partial response (PR)	Dose Expansion-mCRPC	Up to 5 years
Objective response per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1	Dose Expansion-ccRCC	Up to 5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
CompR based on ≥50% decline of PSA from baseline and/or confirmed radiographic assessment of CR or PR	Dose Escalation-mCRPC	Up to 5 years
Percentage of participants with ≥50% reduction of PSA	Dose Escalation and Dose Expansion Phases - mCRPC cohorts	Up to 5 years
Percentage of participants with ≥90% reduction in PSA	Dose Escalation and Dose Expansion - mCRPC cohorts	Up to 5 years
Concentration of REGN15505 in serum	Dose Escalation and Expansion	Up to 5 years
Occurrence of Anti Drug Antibodies (ADA) against REGN15505	Dose Escalation and Expansion	Up to 5 years
Occurrence of ADA against REGN4336	Dose Escalation and Expansion	Up to 5 years
Magnitude of ADA against REGN15505	Dose Escalation and Expansion	Up to 5 years
Magnitude of ADA against REGN4336	Dose Escalation and Expansion	Up to 5 years

Collaborators and Investigators

• Sponsor: Regeneron Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Estimated): May 25, 2026
• Primary Completion (Estimated): September 20, 2030
• Study Completion (Estimated): September 20, 2030

Study Registration Dates

• First Submitted: May 11, 2026
• First Submitted That Met QC Criteria: May 11, 2026
• First Posted (Actual): May 18, 2026

Study Record Updates

• Last Update Posted (Actual): May 18, 2026
• Last Update Submitted That Met QC Criteria: May 11, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: PSMA; 4-1BB; Cemiplimab; REGN4336; REGN15505
• 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; cemiplimab
• Other Study ID Numbers: R15505-ONC-24144

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