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

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

This study is researching an investigational drug called REGN4336. Some participants may receive additional investigational drugs in combination with REGN4336. These additional drugs include REGN5678, cemiplimab and sarilumab.

The main purpose of this study is to determine the safety, tolerability (how the body reacts to the drug) and effectiveness of REGN4336 alone, in combination with cemiplimab, or in combination with REGN5678. REGN4336, cemiplimab and REGN5678 are a type of treatment for cancer called immunotherapy,and are intended to activate T-cells to attack cancer cells.

This study has 2 parts. The purpose of Part 1 is to determine a safe dose of REGN4336 when given alone or when given in combination with cemiplimab or REGN5678. The purpose of Part 2 is to use the REGN4336 dose(s) determined in Part 1 to further test how well REGN4336 works to shrink tumors either when given alone or in combination with cemiplimab or REGN5678.

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

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

Study Overview

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

• Study Type: Interventional
• Enrollment (Estimated): 370
• 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 Cancer Center
  • Kentucky
    • Louisville, Kentucky, United States, 40207
      • Recruiting
      • Norton Cancer Institute
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • Recruiting
      • University of Maryland, Greenebaum Comprehensive 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
  • Ohio
    • Columbus, Ohio, United States, 43210
      • Recruiting
      • James Cancer Hospital and Solove Research Institute at The Ohio State University Comprehensive Cancer Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Recruiting
      • University of Pennsylvania Perelman Center for Advanced Medicine
    • Philadelphia, Pennsylvania, United States, 19111
      • Withdrawn
      • Fox Chase Cancer Center
    • Philadelphia, Pennsylvania, United States, 19107
      • Recruiting
      • Thomas Jefferson University, Sidney Kimmel Center, Clinical Research Organization
  • Texas
    • Houston, Texas, United States, 77030
      • Recruiting
      • MD Anderson Cancer Center
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Recruiting
      • Froedtert and 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 that has progressed within 6 months prior to screening, according to 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 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 or immune-modulating therapy (except for Sipuleucel-T) within 5 half-lives of first dose of study therapy, as described in the protocol
3. Has received prior PSMA-targeting therapy. Exception: Prior therapy with approved PSMA-targeted radioligand(s) is permitted
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, 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

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Module 1- Monotherapy; REGN4336	Drug: REGN4336; Administered once weekly (QW) by subcutaneous (SC) injection, or intravenous (IV) infusion; Drug: Sarilumab; Administered once by IV infusion as prophylaxis prior to REGN4336 IV; Other Names: SAR153191; REGN88
Experimental: Module 2-Combo Therapy; REGN4336 + Cemiplimab	Drug: Cemiplimab; Administered concomitantly every 3 weeks (Q3W) by IV infusion; Other Names: REGN2810; Drug: REGN4336; Administered once weekly (QW) by subcutaneous (SC) injection, or intravenous (IV) infusion; Drug: Sarilumab; Administered once by IV infusion as prophylaxis prior to REGN4336 IV; Other Names: SAR153191; REGN88
Experimental: Module 3-Combo Therapy; REGN4336 + REGN5678	Drug: REGN4336; Administered once weekly (QW) by subcutaneous (SC) injection, or intravenous (IV) infusion; Drug: Sarilumab; Administered once by IV infusion as prophylaxis prior to REGN4336 IV; Other Names: SAR153191; REGN88; Drug: REGN5678; Administered concomitantly QW by IV infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of dose-limiting toxicities (DLTs)	Dose escalation	28 days, up to 42 days
Incidence and severity of treatment-emergent adverse events (TEAEs)	Dose escalation	Up to 5 years
Number of patients with grade ≥3 laboratory abnormalities	Dose escalation	Up to 5 years
Incidence and severity of Immune-mediated Adverse Events (imAEs)	Dose escalation	Up to 5 years
Incidence and severity of Serious Adverse Events (SAEs)	Dose escalation	Up to 5 years
Incidence and severity of adverse event of special interest (AESIs)	Dose escalation	Up to 5 years
REGN4336 monotherapy concentrations in serum	Dose escalation	Up to 5 years
REGN4336 concentrations in serum in combination with cemiplimab	Dose escalation	Up to 5 years
REGN4336 concentrations in serum in combination with REGN5678	Dose escalation	Up to 5 years
Objective response rate (ORR) per modified per modified Prostate Cancer Working Group 3 (PCWG3) criteria	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
Number of patients with grade ≥3 laboratory abnormalities	Dose expansion	Up to 5 years
Anti-drug antibodies (ADA) to REGN4336	Module 1	Up to 5 years
ADA to REGN4336 and cemiplimab	Module 2	Up to 5 years
ORR per modified per modified PCWG3 criteria	Dose Escalation	Up to 5 years
Incidence and severity of imAEs	Dose expansion	Up to 5 years
Incidence and severity of AESIs	Dose expansion	Up to 5 years
REGN4336 monotherapy concentrations in serum	Dose expansion	Up to 5 years
REGN4336 concentrations in serum in combination with cemiplimab	Dose expansion	Up to 5 years
REGN4336 concentrations in serum in combination with REGN5678	Dose expansion	Up to 5 years
Percentage of patients with ≥50% reduction in prostate specific antigen (PSA) from baseline, confirmed by a second PSA test ≥3 weeks later	Dose escalation and expansion	Up to 5 years
Percentage of patients with ≥90% reduction in PSA from baseline, confirmed by a second PSA test ≥3 weeks later	Dose escalation and expansion	UP to 5 years
ADA to REGN4336 and REGN5678	Module 3	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): January 14, 2027
• Study Completion (Estimated): January 14, 2027

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 (Estimated): February 7, 2024
• Last Update Submitted That Met QC Criteria: February 5, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Treatment-experienced metastatic castration-resistant prostate cancer (mCRPC)
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Urogenital Diseases; Male Urogenital Diseases; Genital Diseases, Male; Genital Diseases; Prostatic Neoplasms; Antineoplastic Agents; Antineoplastic Agents, Immunological; Cemiplimab
• Other Study ID Numbers: R4336-ONC-20104; 2022-502130-17-00 (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, 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.
• 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