Neoadjuvant Cemiplimab for the Treatment of Resectable NSCLC, HCC, and HNSCC in Adult Patients

Non-small Cell Lung Cancer Clinical Trial

Official title:

A Multi-Cohort Exploratory Study of Neoadjuvant Cemiplimab for the Treatment of Resectable NSCLC, HCC, and HNSCC

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03916627
• Other study ID #: R2810-ONC-1866
• Status: Recruiting
• Phase: Phase 2
• Start date: July 23, 2019
• Est. completion date: February 26, 2031

Study information

• Verified date: May 2023
• Source: Regeneron Pharmaceuticals
• Contact: Clinical Trials Administrator
• Phone: 844-734-6643
• Email: clinicaltrials[@]regeneron.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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)

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 73
• Est. completion date: February 26, 2031
• Est. primary completion date: April 22, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Key Inclusion Criteria:

• Patient must have a known diagnosis of NSCLC, HCC, or HNSCC as defined in the protocol
• Patient must be willing and able to provide blood samples at the indicated time points
• Patient must be willing and able to have excisional or core needle biopsies of tumor prior to initiation of cemiplimab as defined in the protocol
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Patient is determined to be a surgical candidate for resection of their tumor
• Adequate organ and bone marrow function as defined in the protocol

Key Exclusion Criteria:

• Patients who have had any systemic anti-cancer therapy or radiotherapy within 6 months prior to entering the study for their current tumor or a different primary tumor
• Patients whose tumor burden, or pace of tumor growth, in the opinion of the Investigator will not permit delaying surgery
• Patients who have participated in a study of an investigational agent or an investigational device within 4 weeks of study therapy or 5 half-lives (whichever is longer)
• Patients who have had major surgery within 14 days prior to initiation of neoadjuvant Therapy
• Patients with metastatic disease for whom the intent of surgery would not be curative
• Uncontrolled, intercurrent illness as defined in the protocol and as determined by the Investigator
• Is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study treatment
• Has active autoimmune disease that has required systemic treatment in the past 1 year
• Has a known, additional malignancy that is progressing and/or requires active treatment. Exceptions include patients with: basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy; in situ cervical or anal cancer; prostate cancer on stable dose of hormonal therapy without rising prostate-specific antigen (PSA); breast cancer who have been treated with curative intent, who may be on hormonal therapy.
• Encephalitis, meningitis, or uncontrolled seizures in the year prior to informed consent
• History of interstitial lung disease (eg, idiopathic pulmonary fibrosis, organizing pneumonia) or active, noninfectious pneumonitis that required immune-suppressive doses of glucocorticoids to assist with management. A history of radiation pneumonitis in the radiation field is permitted as long as pneumonitis resolved =6 months prior to study treatment.
• Uncontrolled infection with human immunodeficiency virus (HIV), HBV or hepatitis C infection (HCV); or diagnosis of immunodeficiency as defined in the protocol
• NSCLC cohorts only: Patients do not have a history of smoking. History of smoking is defined as smoking =100 cigarettes in a lifetime.
• NSCLC cohorts only: Patients with tumors tested positive for epidermal growth factor receptor (EGFR) gene mutations, anaplastic lymphoma kinase (ALK) gene translocations, or c-ros oncogene 1 (ROS1) fusions. Note: Other protocol defined Inclusion/Exclusion criteria apply

Related Conditions & MeSH terms

• Carcinoma
• Head and Neck Squamous Cell Carcinoma
• Hepatocellular Carcinoma
• Non-small Cell Lung Cancer
• Squamous Cell Carcinoma of Head and Neck

Intervention

Drug:
• cemiplimab
Administered intravenous (IV)
• Platinum Doublet
Administered intravenous (IV)
• fianlimab
Administered IV

Locations

Country	Name	City	State
United States	Icahn School of Medicine at Mount Sinai	New York	New York

Sponsors (1)

Lead Sponsor	Collaborator
Regeneron Pharmaceuticals

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Major pathologic response (MPR) at time of surgery for the NSCLC cohorts	Cohorts A1, A2, A3	At time of surgery
Primary	Significant tumor necrosis (STN) at time of surgery is the primary endpoint for the HCC cohorts	Cohort B, B2, B3	At time of surgery
Primary	Major treatment effect (MTE) at time of surgery is the primary endpoint for the HNSCC cohort	Cohort C	At time of surgery
Secondary	Delay to surgery	Defined as surgery >28 days following the end of the second cycle of cohort specific neoadjuvant therapy	Surgery >28 days following the end of the cycle of last dose of cemiplimab
Secondary	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.	Up to 60 months following surgery
Secondary	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	Up to 60 months following surgery
Secondary	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	Up to 60 months following surgery
Secondary	Overall survival (OS)	Defined as the time from the first study treatment and date of death for any reason	Up to 60 months following surgery
Secondary	OS rate		12 months
Secondary	OS rate		18 months
Secondary	OS rate		24 months
Secondary	OS rate		36 months
Secondary	OS rate		48 months
Secondary	OS rate		60 months
Secondary	Incidence of treatment emergent adverse events (TEAEs)	Grade 3 or higher per Common Terminology Criteria for Adverse Events (CTCAE V5.0)	Up to 60 months following surgery
Secondary	Incidence of imAEs	Grade 3 or higher per Common Terminology Criteria for Adverse Events (CTCAE V5.0)	Up to 60 months following surgery
Secondary	Incidence of SAEs	Grade 3 or higher per Common Terminology Criteria for Adverse Events (CTCAE V5.0)	Up to 60 months following surgery
Secondary	Incidence of deaths		Up to 60 months following surgery
Secondary	Incidence of laboratory abnormalities	Grade 3 or higher per Common Terminology Criteria for Adverse Events (CTCAE V5.0)	Up to 60 months following surgery
Secondary	Change in tumor-infiltrating CD8 T-cell density	Defined as the change from baseline to the time of surgery	Baseline to time of surgery