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

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

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 Overview

• Status: Active, not recruiting
• Conditions: Hepatocellular Carcinoma; Non-small Cell Lung Cancer; Head and Neck Squamous Cell Carcinoma
• Intervention / Treatment: Drug: cemiplimab; Drug: Platinum Doublet; Drug: fianlimab

• Study Type: Interventional
• Enrollment (Actual): 65
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10029
      • Icahn School of Medicine at Mount Sinai

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

7

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort B; Cemiplimab prior to surgery; cemiplimab post surgery (HCC)	Drug: cemiplimab; Administered intravenous (IV); Other Names: REGN2810; Libtayo
Experimental: Cohort B2; SBRT 8 Gy X 3 fractions followed by cemiplimab prior to surgery; cemiplimab post surgery (HCC)	Drug: cemiplimab; Administered intravenous (IV); Other Names: REGN2810; Libtayo
Experimental: Cohort A1; Cemiplimab prior to surgery; cemiplimab and platinum doublet post surgery (NSCLC) Not open for accrual	Drug: cemiplimab; Administered intravenous (IV); Other Names: REGN2810; Libtayo; Drug: Platinum Doublet; Administered intravenous (IV)
Experimental: Cohort A2; Cemiplimab and platinum doublet prior to surgery; cemiplimab and platinum doublet post surgery (NSCLC) Not open for accrual	Drug: cemiplimab; Administered intravenous (IV); Other Names: REGN2810; Libtayo; Drug: Platinum Doublet; Administered intravenous (IV)
Experimental: Cohort A3; Platinum doublet prior to surgery; cemiplimab and platinum doublet post surgery (NSCLC) Not open for accrual	Drug: cemiplimab; Administered intravenous (IV); Other Names: REGN2810; Libtayo; Drug: Platinum Doublet; Administered intravenous (IV)
Experimental: Cohort C; Cemiplimab prior to surgery; standard of care radiation and/or chemotherapy followed by cemiplimab post surgery (HNSCC) Not open for accrual	Drug: cemiplimab; Administered intravenous (IV); Other Names: REGN2810; Libtayo
Experimental: Cohort B3; Cemiplimab and fianlimab before and after surgery (HCC)	Drug: cemiplimab; Administered intravenous (IV); Other Names: REGN2810; Libtayo; Drug: fianlimab; Administered IV; Other Names: REGN3767

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Major pathologic response (MPR) at time of surgery for the NSCLC cohorts	Cohorts A1, A2, A3	At time of surgery
Major treatment effect (MTE) at time of surgery is the primary endpoint for the HNSCC cohort	Cohort C	At time of surgery
Significant tumor necrosis (STN) at time of surgery is the primary endpoint for the HCC cohorts	Cohort B, B2, B3	At time of surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
OS rate		12 months
OS rate		18 months
OS rate		24 months
OS rate		36 months
OS rate		48 months
OS rate		60 months
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
Incidence of SAEs	Grade 3 or higher per Common Terminology Criteria for Adverse Events (CTCAE V5.0)	Up to 60 months following surgery
Incidence of deaths		Up to 60 months following surgery
Incidence of laboratory abnormalities	Grade 3 or higher per Common Terminology Criteria for Adverse Events (CTCAE V5.0)	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	Baseline to time of surgery
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
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
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
Incidence of imAEs	Grade 3 or higher per Common Terminology Criteria for Adverse Events (CTCAE V5.0)	Up to 60 months following surgery

Collaborators and Investigators

• Sponsor: Regeneron Pharmaceuticals
• Collaborators: Sanofi
• Investigators: Study Director: Clinical Trial Management, Regeneron Pharmaceuticals

Publications and helpful links

General Publications

• Marron TU, Fiel MI, Hamon P, Fiaschi N, Kim E, Ward SC, Zhao Z, Kim J, Kennedy P, Gunasekaran G, Tabrizian P, Doroshow D, Legg M, Hammad A, Magen A, Kamphorst AO, Shareef M, Gupta NT, Deering R, Wang W, Wang F, Thanigaimani P, Mani J, Troncoso L, Tabachnikova A, Chang C, Akturk G, Buckup M, Hamel S, Ioannou G, Hennequin C, Jamal H, Brown H, Bonaccorso A, Labow D, Sarpel U, Rosenbloom T, Sung MW, Kou B, Li S, Jankovic V, James N, Hamon SC, Cheung HK, Sims JS, Miller E, Bhardwaj N, Thurston G, Lowy I, Gnjatic S, Taouli B, Schwartz ME, Merad M. Neoadjuvant cemiplimab for resectable hepatocellular carcinoma: a single-arm, open-label, phase 2 trial. Lancet Gastroenterol Hepatol. 2022 Mar;7(3):219-229. doi: 10.1016/S2468-1253(21)00385-X. Epub 2022 Jan 20.
• D'Alessio A, Stefanini B, Blanter J, Adegbite B, Crowley F, Yip V, Slater S, Fulgenzi CAM, Celsa C, Manfredi GF, Pai M, Goldin RD, Ward SC, Fiel MI, Shu DH, Su YY, Cortellini A, Baretti M, Anders R, Yarchoan M, Hsu C, Marron TU, Pinato DJ. Pathological response following neoadjuvant immune checkpoint inhibitors in patients with hepatocellular carcinoma: a cross-trial, patient-level analysis. Lancet Oncol. 2024 Nov;25(11):1465-1475. doi: 10.1016/S1470-2045(24)00457-1. Epub 2024 Oct 19.

Study record dates

Study Major Dates

• Study Start (Actual): July 23, 2019
• Primary Completion (Actual): March 31, 2025
• Study Completion (Estimated): May 14, 2030

Study Registration Dates

• First Submitted: April 5, 2019
• First Submitted That Met QC Criteria: April 12, 2019
• First Posted (Actual): April 16, 2019

Study Record Updates

• Last Update Posted (Actual): April 6, 2026
• Last Update Submitted That Met QC Criteria: March 30, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: NSCLC; HCC; Resectable; HNSCC
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Neoplasms by Histologic Type; Digestive System Neoplasms; Digestive System Diseases; Lung Diseases; Head and Neck Neoplasms; Liver Diseases; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Liver Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Carcinoma; Carcinoma, Bronchogenic; Bronchial Neoplasms; Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck; Carcinoma, Hepatocellular; Carcinoma, Non-Small-Cell Lung; Antineoplastic Agents, Immunological; Antineoplastic Agents; cemiplimab
• Other Study ID Numbers: R2810-ONC-1866

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: All Individual Patient Data (IPD) that underlie publicly available results will be considered for sharing
• IPD Sharing Time Frame: Individual anonymized participant data will be considered for sharing once the indication has been approved by a regulatory body, if there is legal authority to share the data and there is not a reasonable likelihood of participant re-identification.
• IPD Sharing Access Criteria: Qualified researchers may request access to anonymized patient level data or aggregate study data 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 the legal authority to share the data, and has made the study results publicly available (eg, scientific publication, scientific conference, clinical trial registry).
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No