This study is being done to better understand whether or not cemiplimab by itself and in combination with other treatments given prior to surgery will cause your tumor to respond in a beneficial way; whether the drug(s) are safe and what side effects they cause; and other details about how they function in the body. One of the treatments that will be combined cemiplimab is another experimental drug called fianlimab. In this form, cemiplimab and fianlimab will each individually be called "study drug" or "study drugs" when combined. Cemiplimab (also known as REGN2810) and fianlimab (also known as REGN3767) are both a type of drug called a monoclonal antibody. Antibodies are proteins naturally found in your blood that fight infections. A monoclonal antibody is a special kind of antibody that is manufactured as a medication to target specific proteins in the body that may be involved in your cancer. * Cemiplimab is a drug that blocks the programmed death receptor 1 (PD-1), a cell receptor on immune cells * Fianlimab is a drug that blocks the action of a protein called lymphocyte activation gene (LAG)-33 (LAG-3)
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
65
Administered intravenous (IV)
Administered intravenous (IV)
Administered IV
Icahn School of Medicine at Mount Sinai
New York, New York, United States
Major pathologic response (MPR) at time of surgery for the NSCLC cohorts
Cohorts A1, A2, A3
Time frame: At time of surgery
Significant tumor necrosis (STN) at time of surgery is the primary endpoint for the HCC cohorts
Cohort B, B2, B3
Time frame: At time of surgery
Major treatment effect (MTE) at time of surgery is the primary endpoint for the HNSCC cohort
Cohort C
Time frame: At time of surgery
Delay to surgery
Defined as surgery \>28 days following the end of the second cycle of cohort specific neoadjuvant therapy
Time frame: Surgery >28 days following the end of the cycle of last dose of cemiplimab
Event-free survival (EFS)
Defined as the time from the first study treatment to the date of disease progression that precluded definitive surgery, or recurrence of tumor after successful surgery, or death from any cause.
Time frame: Up to 60 months following surgery
Disease-free survival (DFS)
Defined as the time from date of surgery until recurrence of tumor or death from any cause after successful surgery and recovery
Time frame: Up to 60 months following surgery
Overall response rate (ORR)
Defined as the percent of patients with a complete response (CR) or partial response (PR) documented by the Investigator per RECIST 1.1. as described in the protocol
Time frame: Up to 60 months following surgery
Overall survival (OS)
Defined as the time from the first study treatment and date of death for any reason
Time frame: Up to 60 months following surgery
OS rate
Time frame: 12 months
OS rate
Time frame: 18 months
OS rate
Time frame: 24 months
OS rate
Time frame: 36 months
OS rate
Time frame: 48 months
OS rate
Time frame: 60 months
Incidence of treatment emergent adverse events (TEAEs)
Grade 3 or higher per Common Terminology Criteria for Adverse Events (CTCAE V5.0)
Time frame: Up to 60 months following surgery
Incidence of imAEs
Grade 3 or higher per Common Terminology Criteria for Adverse Events (CTCAE V5.0)
Time frame: Up to 60 months following surgery
Incidence of SAEs
Grade 3 or higher per Common Terminology Criteria for Adverse Events (CTCAE V5.0)
Time frame: Up to 60 months following surgery
Incidence of deaths
Time frame: Up to 60 months following surgery
Incidence of laboratory abnormalities
Grade 3 or higher per Common Terminology Criteria for Adverse Events (CTCAE V5.0)
Time frame: Up to 60 months following surgery
Change in tumor-infiltrating CD8 T-cell density
Defined as the change from baseline to the time of surgery
Time frame: Baseline to time of surgery
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