Back to resultsA 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
Primary Purpose
Metastatic Castration-resistant Prostate Cancer
Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
REGN4336
Cemiplimab
18F-DCFPyL
Sponsored by
About this trial
This is an interventional treatment trial for Metastatic Castration-resistant Prostate Cancer focused on measuring Treatment-experienced metastatic castration-resistant prostate cancer (mCRPC)
Eligibility Criteria
Key Inclusion Criteria:
- Histologically or cytologically confirmed adenocarcinoma of the prostate without pure small cell carcinoma
- 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
- 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:
- 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
- Has received any previous systemic biologic therapy within 5 half-lives of first dose of study therapy
- Has received prior PSMA-targeting therapy
- 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
- Ongoing or recent (within 5 years) evidence of significant autoimmune disease that required treatment with systemic immunosuppressive treatments
- 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
- 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
Sites / Locations
- Stanford Cancer CenterRecruiting
- Norton Cancer InstituteRecruiting
- University of Maryland, Greenebaum Comprehensive Cancer CenterRecruiting
- Rutgers Cancer Institute of New JerseyRecruiting
- Roswell Park Cancer InstituteRecruiting
- James Cancer Hospital and Solove Research Institute at The Ohio State University Comprehensive Cancer CenterRecruiting
- University of Pennsylvania Perelman Center for Advanced MedicineRecruiting
- Thomas Jefferson University, Sidney Kimmel Center, Clinical Research OrganizationRecruiting
- Fox Chase Cancer Center
- Froedtert and Medical College of WisconsinRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Module 1- Monotherapy
Module 2-Combo Therapy
Arm Description
REGN4336
REGN4336 + Cemiplimab
Outcomes
Primary Outcome Measures
Incidence of dose-limiting toxicities (DLTs)
Dose escalation
Incidence and severity of treatment-emergent adverse events (TEAEs)
Dose escalation
Incidence and severity of Immune-mediated Adverse Events (imAEs)
Dose escalation
Incidence and severity of SAEs
Dose escalation
Incidence and severity of adverse event of special interests (AESIs)
Dose escalation
Number of patients with grade ≥3 laboratory abnormalities
Dose escalation
REGN4336 concentrations in serum
Dose escalation:
As monotherapy or in combination with cemiplimab
ORR per modified per modified Prostate Cancer Working Group 3 (PCWG3) criteria
Dose expansion
Secondary Outcome Measures
ORR per modified per modified PCWG3 criteria
Dose Escalation:
Incidence of dose-limiting toxicities (DLTs)
Dose expansion
Incidence and severity of TEAEs
Dose expansion
Incidence and severity of Immune-mediated Adverse Events
Dose expansion
Incidence and severity of SAEs
Dose expansion
Incidence and severity of adverse event of special interests (AESIs)
Dose expansion
Number of patients with grade ≥3 laboratory abnormalities
Dose expansion
REGN4336 concentrations in serum
Dose expansion:
As monotherapy or in combination with cemiplimab
Percentage of patients with ≥50% reduction prostate specific antigen (PSA) from baseline, confirmed by a second PSA test ≥4 weeks later
Dose escalation and expansion
Percentage of patients with ≥90% reduction prostate specific antigen (PSA) from baseline, confirmed by a second PSA test ≥4 weeks later
Dose escalation and expansion
Anti-drug antibodies (ADA) to REGN4336
Module 1
ADA to REGN4336 and cemiplimab
Module 2
Full Information
NCT ID
NCT05125016
First Posted
October 25, 2021
Last Updated
September 6, 2023
Sponsor
Regeneron Pharmaceuticals
1. Study Identification
Unique Protocol Identification Number
NCT05125016
Brief Title
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
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
Study Type
Interventional
2. Study Status
Record Verification Date
July 2023
Overall Recruitment Status
Recruiting
Study Start Date
November 30, 2021 (Actual)
Primary Completion Date
August 4, 2026 (Anticipated)
Study Completion Date
August 4, 2026 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Regeneron Pharmaceuticals
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. 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
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Metastatic Castration-resistant Prostate Cancer
Keywords
Treatment-experienced metastatic castration-resistant prostate cancer (mCRPC)
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
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)
Allocation
Non-Randomized
Enrollment
199 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Module 1- Monotherapy
Arm Type
Experimental
Arm Description
REGN4336
Arm Title
Module 2-Combo Therapy
Arm Type
Experimental
Arm Description
REGN4336 + Cemiplimab
Intervention Type
Drug
Intervention Name(s)
REGN4336
Intervention Description
Administered once weekly (QW) or every 3 weeks (Q3W) by subcutaneous (SC) injection.
Intervention Type
Drug
Intervention Name(s)
Cemiplimab
Other Intervention Name(s)
REGN2810, Libtayo
Intervention Description
Administered concomitantly every 3 weeks (Q3W) by IV infusion
Intervention Type
Other
Intervention Name(s)
18F-DCFPyL
Intervention Description
Prostate-specific membrane antigen (PSMA) Positron emission tomography (PET)/Computer tomography (CT) imaging agent to be used at select sites
Primary Outcome Measure Information:
Title
Incidence of dose-limiting toxicities (DLTs)
Description
Dose escalation
Time Frame
28 days, up to 42 days
Title
Incidence and severity of treatment-emergent adverse events (TEAEs)
Description
Dose escalation
Time Frame
Up to 5 years
Title
Incidence and severity of Immune-mediated Adverse Events (imAEs)
Description
Dose escalation
Time Frame
Up to 5 years
Title
Incidence and severity of SAEs
Description
Dose escalation
Time Frame
Up to 5 years
Title
Incidence and severity of adverse event of special interests (AESIs)
Description
Dose escalation
Time Frame
Up to 5 years
Title
Number of patients with grade ≥3 laboratory abnormalities
Description
Dose escalation
Time Frame
Up to 5 years
Title
REGN4336 concentrations in serum
Description
Dose escalation:
As monotherapy or in combination with cemiplimab
Time Frame
Up to 5 years
Title
ORR per modified per modified Prostate Cancer Working Group 3 (PCWG3) criteria
Description
Dose expansion
Time Frame
Up to 5 years
Secondary Outcome Measure Information:
Title
ORR per modified per modified PCWG3 criteria
Description
Dose Escalation:
Time Frame
Up to 5 years
Title
Incidence of dose-limiting toxicities (DLTs)
Description
Dose expansion
Time Frame
Up to 28 days
Title
Incidence and severity of TEAEs
Description
Dose expansion
Time Frame
Up to 5 years
Title
Incidence and severity of Immune-mediated Adverse Events
Description
Dose expansion
Time Frame
Up to 5 years
Title
Incidence and severity of SAEs
Description
Dose expansion
Time Frame
Up to 5 years
Title
Incidence and severity of adverse event of special interests (AESIs)
Description
Dose expansion
Time Frame
Up to 5 years
Title
Number of patients with grade ≥3 laboratory abnormalities
Description
Dose expansion
Time Frame
Up to 5 years
Title
REGN4336 concentrations in serum
Description
Dose expansion:
As monotherapy or in combination with cemiplimab
Time Frame
Up to 5 years
Title
Percentage of patients with ≥50% reduction prostate specific antigen (PSA) from baseline, confirmed by a second PSA test ≥4 weeks later
Description
Dose escalation and expansion
Time Frame
Up to 5 years
Title
Percentage of patients with ≥90% reduction prostate specific antigen (PSA) from baseline, confirmed by a second PSA test ≥4 weeks later
Description
Dose escalation and expansion
Time Frame
UP to 5 years
Title
Anti-drug antibodies (ADA) to REGN4336
Description
Module 1
Time Frame
Up to 5 years
Title
ADA to REGN4336 and cemiplimab
Description
Module 2
Time Frame
Up to 5 years
10. Eligibility
Sex
Male
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Key Inclusion Criteria:
Histologically or cytologically confirmed adenocarcinoma of the prostate without pure small cell carcinoma
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
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:
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
Has received any previous systemic biologic therapy within 5 half-lives of first dose of study therapy
Has received prior PSMA-targeting therapy
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
Ongoing or recent (within 5 years) evidence of significant autoimmune disease that required treatment with systemic immunosuppressive treatments
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
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Clinical Trials Administrator
Phone
844-734-6643
Email
clinicaltrials@regeneron.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Trial Management
Organizational Affiliation
Regeneron Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
Stanford Cancer Center
City
Palo Alto
State/Province
California
ZIP/Postal Code
94304
Country
United States
Individual Site Status
Recruiting
Facility Name
Norton Cancer Institute
City
Louisville
State/Province
Kentucky
ZIP/Postal Code
40207
Country
United States
Individual Site Status
Recruiting
Facility Name
University of Maryland, Greenebaum Comprehensive Cancer Center
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21201
Country
United States
Individual Site Status
Recruiting
Facility Name
Rutgers Cancer Institute of New Jersey
City
New Brunswick
State/Province
New Jersey
ZIP/Postal Code
08901
Country
United States
Individual Site Status
Recruiting
Facility Name
Roswell Park Cancer Institute
City
Buffalo
State/Province
New York
ZIP/Postal Code
14263
Country
United States
Individual Site Status
Recruiting
Facility Name
James Cancer Hospital and Solove Research Institute at The Ohio State University Comprehensive Cancer Center
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43210
Country
United States
Individual Site Status
Recruiting
Facility Name
University of Pennsylvania Perelman Center for Advanced Medicine
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Individual Site Status
Recruiting
Facility Name
Thomas Jefferson University, Sidney Kimmel Center, Clinical Research Organization
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19107
Country
United States
Individual Site Status
Recruiting
Facility Name
Fox Chase Cancer Center
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19111
Country
United States
Individual Site Status
Withdrawn
Facility Name
Froedtert and Medical College of Wisconsin
City
Milwaukee
State/Province
Wisconsin
ZIP/Postal Code
53226
Country
United States
Individual Site Status
Recruiting
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing 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 URL
https://vivli.org/
Learn more about this trial
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
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