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

• ClinicalTrials.gov Identifier: NCT05125016
• Recruitment Status: Recruiting
• First Posted: November 18, 2021
• Last Update Posted: May 22, 2023
• Sponsor: Regeneron Pharmaceuticals
• Information provided by (Responsible Party): Regeneron Pharmaceuticals

Study Description

Brief Summary:

The primary objective of the study is:

Dose Escalation:

• To assess the safety, tolerability, and pharmacokinetics (PK) and to determine recommended phase 2 dosing regimen (RP2DR) of REGN4336 separately as monotherapy or in combination with cemiplimab

Dose Expansion:

• To assess preliminary anti-tumor activity of REGN4336 as monotherapy or in combination with cemiplimab as measured by objective response rate (ORR) per modified Prostate Cancer Working Group (PCWG3) criteria

The secondary objectives of the study are:

Dose Escalation:

• To assess preliminary anti-tumor activity of REGN4336 as monotherapy or in combination with cemiplimab as measured by ORR per modified PCWG3 criteria

Dose Expansion:

• To characterize the safety profile in each expansion cohort
• To characterize the PK of REGN4336 as monotherapy or in combination with cemiplimab

In both Dose Escalation and Dose Expansion:

• To assess preliminary anti-tumor activity of REGN4336 as monotherapy or in combination with cemiplimab as measured by prostate specific antigen (PSA) decline
• To evaluate immunogenicity of REGN4336 in Module 1 and immunogenicity of REGN4336 and cemiplimab in Module 2

Condition or disease	Intervention/treatment	Phase
Metastatic Castration-resistant Prostate Cancer	Drug: REGN4336; Drug: Cemiplimab; Other: 18F-DCFPyL	Phase 1; Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 199 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: The study contains 2 separate modules in parallel: monotherapy with REGN4336 (Module 1) and combination therapy with REGN4336 and cemiplimab (Module 2). Both modules contain independent dose escalation cohorts and up to 2 recommended phase 2 dose regimens during dose expansion.
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase 1/2 Study of REGN4336 (a PSMAXCD3 Bispecific Antibody) Administered Alone or in Combination With Cemiplimab in Patients With Metastatic Castration-Resistant Prostate Cancer
• Actual Study Start Date: November 30, 2021
• Estimated Primary Completion Date: August 4, 2026
• Estimated Study Completion Date: August 4, 2026

Arms and Interventions

Arm	Intervention/treatment
Experimental: Module 1- Monotherapy; REGN4336	Drug: REGN4336; Administered once weekly (QW) or every 3 weeks (Q3W) by subcutaneous (SC) injection.; Other: 18F-DCFPyL; Prostate-specific membrane antigen (PSMA) Positron emission tomography (PET)/Computer tomography (CT) imaging agent to be used at select sites
Experimental: Module 2-Combo Therapy; REGN4336 + Cemiplimab	Drug: REGN4336; Administered once weekly (QW) or every 3 weeks (Q3W) by subcutaneous (SC) injection.; Drug: Cemiplimab; Administered concomitantly every 3 weeks (Q3W) by IV infusion; Other Names: REGN2810; Libtayo; Other: 18F-DCFPyL; Prostate-specific membrane antigen (PSMA) Positron emission tomography (PET)/Computer tomography (CT) imaging agent to be used at select sites

Outcome Measures

Primary Outcome Measures :

1. Incidence of dose-limiting toxicities (DLTs) [ Time Frame: 28 days, up to 42 days ]
   Dose escalation
2. Incidence and severity of treatment-emergent adverse events (TEAEs) [ Time Frame: Up to 5 years ]
   Dose escalation
3. Incidence and severity of Immune-mediated Adverse Events (imAEs) [ Time Frame: Up to 5 years ]
   Dose escalation
4. Incidence and severity of SAEs [ Time Frame: Up to 5 years ]
   Dose escalation
5. Incidence and severity of adverse event of special interests (AESIs) [ Time Frame: Up to 5 years ]
   Dose escalation
6. Number of patients with grade ≥3 laboratory abnormalities [ Time Frame: Up to 5 years ]
   Dose escalation
7. REGN4336 concentrations in serum [ Time Frame: Up to 5 years ]

   Dose escalation:

   As monotherapy or in combination with cemiplimab

8. ORR per modified per modified Prostate Cancer Working Group 3 (PCWG3) criteria [ Time Frame: Up to 5 years ]
   Dose expansion

Secondary Outcome Measures :

1. ORR per modified per modified PCWG3 criteria [ Time Frame: Up to 5 years ]
   Dose Escalation:
2. Incidence of dose-limiting toxicities (DLTs) [ Time Frame: Up to 28 days ]
   Dose expansion
3. Incidence and severity of TEAEs [ Time Frame: Up to 5 years ]
   Dose expansion
4. Incidence and severity of Immune-mediated Adverse Events [ Time Frame: Up to 5 years ]
   Dose expansion
5. Incidence and severity of SAEs [ Time Frame: Up to 5 years ]
   Dose expansion
6. Incidence and severity of adverse event of special interests (AESIs) [ Time Frame: Up to 5 years ]
   Dose expansion
7. Number of patients with grade ≥3 laboratory abnormalities [ Time Frame: Up to 5 years ]
   Dose expansion
8. REGN4336 concentrations in serum [ Time Frame: Up to 5 years ]

   Dose expansion:

   As monotherapy or in combination with cemiplimab

9. Percentage of patients with ≥50% reduction prostate specific antigen (PSA) from baseline, confirmed by a second PSA test ≥4 weeks later [ Time Frame: Up to 5 years ]
   Dose escalation and expansion
10. Percentage of patients with ≥90% reduction prostate specific antigen (PSA) from baseline, confirmed by a second PSA test ≥4 weeks later [ Time Frame: UP to 5 years ]
    Dose escalation and expansion
11. Anti-drug antibodies (ADA) to REGN4336 [ Time Frame: Up to 5 years ]
    Module 1
12. ADA to REGN4336 and cemiplimab [ Time Frame: Up to 5 years ]
    Module 2

Eligibility Criteria

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

Criteria

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 that has progressed within 6 months prior to screening as defined in the protocol
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 therapy within 3 weeks of dosing or has not yet recovered (ie, grade ≤1 or baseline) from any acute toxicities
2. Has received any previous systemic biologic therapy within 5 half-lives of first dose of study therapy
3. Has received prior PSMA-targeting therapy
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 or hepatitis C infection; or diagnosis of immunodeficiency

NOTE: Other protocol defined Inclusion/Exclusion Criteria apply

Contacts and Locations

Contacts

Contact: Clinical Trials Administrator; 844-734-6643; clinicaltrials@regeneron.com

Locations

United States, California

Stanford Cancer Center; Recruiting

Palo Alto, California, United States, 94304

United States, Kentucky

Norton Cancer Institute; Recruiting

Louisville, Kentucky, United States, 40207

United States, Maryland

University of Maryland, Greenebaum Comprehensive Cancer Center; Recruiting

Baltimore, Maryland, United States, 21201

United States, New Jersey

Rutgers Cancer Institute of New Jersey; Recruiting

New Brunswick, New Jersey, United States, 08901

United States, New York

Roswell Park Cancer Institute; Recruiting

Buffalo, New York, United States, 14263

United States, Ohio

James Cancer Hospital and Solove Research Institute at The Ohio State University Comprehensive Cancer Center; Recruiting

Columbus, Ohio, United States, 43210

United States, Pennsylvania

University of Pennsylvania Perelman Center for Advanced Medicine; Recruiting

Philadelphia, Pennsylvania, United States, 19104

Thomas Jefferson University, Sidney Kimmel Center, Clinical Research Organization; Recruiting

Philadelphia, Pennsylvania, United States, 19107

Fox Chase Cancer Center; Withdrawn

Philadelphia, Pennsylvania, United States, 19111

United States, Wisconsin

Froedtert and Medical College of Wisconsin; Recruiting

Milwaukee, Wisconsin, United States, 53226

Sponsors and Collaborators

Regeneron Pharmaceuticals

Investigators

• Study Director: Clinical Trial Management; Regeneron Pharmaceuticals

More Information

• Responsible Party: Regeneron Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT05125016
• Other Study ID Numbers: R4336-ONC-20104; 2022-502130-17-00 ( Other Identifier: EUCT Number )
• First Posted: November 18, 2021
• Last Update Posted: May 22, 2023
• Last Verified: August 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: All Individual Patient Data (IPD) that underlie publicly available results will be considered for sharing
• Supporting Materials: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (CSR); Analytic Code
• 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, has made the study results publicly available (e.g., scientific publication, scientific conference, clinical trial registry), has the legal authority to share the data, and has ensured the ability to protect participant privacy.
• 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
• URL: https://vivli.org/

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Regeneron Pharmaceuticals:

Treatment-experienced metastatic castration-resistant prostate cancer (mCRPC)

Additional relevant MeSH terms:

Prostatic Neoplasms; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases; Cemiplimab; Antineoplastic Agents, Immunological; Antineoplastic Agents