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 Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
370
Administered once weekly (QW) by subcutaneous (SC) injection, or intravenous (IV) infusion
Administered concomitantly every 3 weeks (Q3W) by IV infusion
Administered concomitantly QW by IV infusion
Administered once by IV infusion as prophylaxis prior to REGN4336 IV
Stanford University Medical Center - Blake Wilbur Drive
Palo Alto, California, United States
RECRUITINGNorton Cancer Institute
Louisville, Kentucky, United States
RECRUITINGUniversity of Maryland Greenebaum Cancer Center
Baltimore, Maryland, United States
RECRUITINGRutgers Cancer Institute of New Jersey
New Brunswick, New Jersey, United States
RECRUITINGRoswell Park Cancer Institute
Buffalo, New York, United States
RECRUITINGAtrium Health Levine Cancer Institute
Charlotte, North Carolina, United States
RECRUITINGThe Ohio State University James Cancer Hospital
Columbus, Ohio, United States
RECRUITINGPenn Medicine University of Pennsylvania Health System
Philadelphia, Pennsylvania, United States
RECRUITINGThomas Jefferson University Hospital
Philadelphia, Pennsylvania, United States
RECRUITINGFox Chase Cancer Center
Philadelphia, Pennsylvania, United States
WITHDRAWN...and 3 more locations
Incidence of dose-limiting toxicities (DLTs)
Dose escalation
Time frame: 28 days, up to 42 days
Incidence and severity of treatment-emergent adverse events (TEAEs)
Dose escalation
Time frame: Up to 5 years
Incidence and severity of Immune-mediated Adverse Events (imAEs)
Dose escalation
Time frame: Up to 5 years
Incidence and severity of Serious Adverse Events (SAEs)
Dose escalation
Time frame: Up to 5 years
Incidence and severity of adverse event of special interest (AESIs)
Dose escalation
Time frame: Up to 5 years
Number of patients with grade ≥3 laboratory abnormalities
Dose escalation
Time frame: Up to 5 years
REGN4336 monotherapy concentrations in serum
Dose escalation
Time frame: Up to 5 years
REGN4336 concentrations in serum in combination with cemiplimab
Dose escalation
Time frame: Up to 5 years
REGN4336 concentrations in serum in combination with REGN5678
Dose escalation
Time frame: Up to 5 years
Objective response rate (ORR) per modified per modified Prostate Cancer Working Group 3 (PCWG3) criteria
Dose expansion
Time frame: Up to 5 years
ORR per modified per modified PCWG3 criteria
Dose Escalation
Time frame: Up to 5 years
Incidence and severity of TEAEs
Dose expansion
Time frame: Up to 5 years
Incidence and severity of imAEs
Dose expansion
Time frame: Up to 5 years
Incidence and severity of SAEs
Dose expansion
Time frame: Up to 5 years
Incidence and severity of AESIs
Dose expansion
Time frame: Up to 5 years
Number of patients with grade ≥3 laboratory abnormalities
Dose expansion
Time frame: Up to 5 years
REGN4336 monotherapy concentrations in serum
Dose expansion
Time frame: Up to 5 years
REGN4336 concentrations in serum in combination with cemiplimab
Dose expansion
Time frame: Up to 5 years
REGN4336 concentrations in serum in combination with REGN5678
Dose expansion
Time frame: 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
Time frame: Up to 5 years
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Percentage of patients with ≥90% reduction in PSA from baseline, confirmed by a second PSA test ≥3 weeks later
Dose escalation and expansion
Time frame: UP to 5 years
Anti-drug antibodies (ADA) to REGN4336
Module 1
Time frame: Up to 5 years
ADA to REGN4336 and cemiplimab
Module 2
Time frame: Up to 5 years
ADA to REGN4336 and REGN5678
Module 3
Time frame: Up to 5 years