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
- Conditions
- Metastatic Castration-resistant Prostate Cancer
- Interventions
- Registration Number
- NCT05125016
- Lead Sponsor
- Regeneron Pharmaceuticals
- Brief Summary
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)?
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- Male
- Target Recruitment
- 370
-
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, according to 1 of the following:
- PSA progression as defined by a rising PSA level confirmed with an interval of ≥1 week between each assessment
- Radiographic disease progression in soft tissue based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 criteria with or without PSA progression
- 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
-
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
- 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 or immune-modulating therapy (except for Sipuleucel-T) within 5 half-lives of first dose of study therapy, as described in the protocol
- Has received prior PSMA-targeting therapy. Exception: Prior therapy with approved PSMA-targeted radioligand(s) is permitted
- 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, as described in the protocol.
NOTE: Other protocol defined Inclusion/Exclusion Criteria apply
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Module 3-Combo Therapy Sarilumab REGN4336 + REGN5678 Module 1- Monotherapy REGN4336 REGN4336 Module 1- Monotherapy Sarilumab REGN4336 Module 2-Combo Therapy REGN4336 REGN4336 + Cemiplimab Module 2-Combo Therapy Sarilumab REGN4336 + Cemiplimab Module 3-Combo Therapy REGN4336 REGN4336 + REGN5678 Module 3-Combo Therapy REGN5678 REGN4336 + REGN5678 Module 2-Combo Therapy Cemiplimab REGN4336 + Cemiplimab
- Primary Outcome Measures
Name Time Method Incidence and severity of Immune-mediated Adverse Events (imAEs) Up to 5 years Dose escalation
Incidence and severity of Serious Adverse Events (SAEs) Up to 5 years Dose escalation
Incidence and severity of adverse event of special interest (AESIs) Up to 5 years Dose escalation
Number of patients with grade ≥3 laboratory abnormalities Up to 5 years Dose escalation
Incidence of dose-limiting toxicities (DLTs) 28 days, up to 42 days Dose escalation
Incidence and severity of treatment-emergent adverse events (TEAEs) Up to 5 years Dose escalation
REGN4336 monotherapy concentrations in serum Up to 5 years Dose escalation
REGN4336 concentrations in serum in combination with cemiplimab Up to 5 years Dose escalation
REGN4336 concentrations in serum in combination with REGN5678 Up to 5 years Dose escalation
Objective response rate (ORR) per modified per modified Prostate Cancer Working Group 3 (PCWG3) criteria Up to 5 years Dose expansion
- Secondary Outcome Measures
Name Time Method Incidence and severity of AESIs Up to 5 years Dose expansion
REGN4336 monotherapy concentrations in serum Up to 5 years Dose expansion
Anti-drug antibodies (ADA) to REGN4336 Up to 5 years Module 1
ADA to REGN4336 and REGN5678 Up to 5 years Module 3
Incidence and severity of TEAEs Up to 5 years Dose expansion
ORR per modified per modified PCWG3 criteria Up to 5 years Dose Escalation
Incidence and severity of imAEs Up to 5 years Dose expansion
Incidence and severity of SAEs Up to 5 years Dose expansion
REGN4336 concentrations in serum in combination with cemiplimab Up to 5 years Dose expansion
REGN4336 concentrations in serum in combination with REGN5678 Up to 5 years Dose expansion
Percentage of patients with ≥50% reduction in prostate specific antigen (PSA) from baseline, confirmed by a second PSA test ≥3 weeks later Up to 5 years Dose escalation and expansion
ADA to REGN4336 and cemiplimab Up to 5 years Module 2
Percentage of patients with ≥90% reduction in PSA from baseline, confirmed by a second PSA test ≥3 weeks later UP to 5 years Dose escalation and expansion
Number of patients with grade ≥3 laboratory abnormalities Up to 5 years Dose expansion
Trial Locations
- Locations (12)
Atrium Health Levine Cancer Institute
🇺🇸Charlotte, North Carolina, United States
Stanford University Medical Center - Blake Wilbur Drive
🇺🇸Palo Alto, California, United States
Norton Cancer Institute
🇺🇸Louisville, Kentucky, United States
University of Maryland Greenebaum Cancer Center
🇺🇸Baltimore, Maryland, United States
Rutgers Cancer Institute of New Jersey
🇺🇸New Brunswick, New Jersey, United States
Roswell Park Cancer Institute
🇺🇸Buffalo, New York, United States
The Ohio State University James Cancer Hospital
🇺🇸Columbus, Ohio, United States
Penn Medicine University of Pennsylvania Health System
🇺🇸Philadelphia, Pennsylvania, United States
Thomas Jefferson University Hospital
🇺🇸Philadelphia, Pennsylvania, United States
Fox Chase Cancer Center
🇺🇸Philadelphia, Pennsylvania, United States
MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
Medical College of Wisconsin
🇺🇸Milwaukee, Wisconsin, United States