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

NCT03916627 | Active Not Recruiting Phase 2 FDA Drug

• 1 other identifier: R2810-ONC-1866
• Study Type: interventional
• Target: 65
• Locations: 1 country
• Sites: 1

Brief 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)

Conditions

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

Keywords

NSCLC; HCC; HNSCC; Resectable

Outcome Measures

Primary Outcomes (3)

• Major pathologic response (MPR) at time of surgery for the NSCLC cohorts

  Cohorts A1, A2, A3

  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

• Major treatment effect (MTE) at time of surgery is the primary endpoint for the HNSCC cohort

  Cohort C

  At time of surgery

Secondary Outcomes (17)

• Delay to surgery

  Surgery >28 days following the end of the cycle of last dose of cemiplimab

• Event-free survival (EFS)

  Up to 60 months following surgery

• Disease-free survival (DFS)

  Up to 60 months following surgery

• Overall response rate (ORR)

  Up to 60 months following surgery

• Overall survival (OS)

  Up to 60 months following surgery

Study Arms (7)

Cohort A1

EXPERIMENTAL

Cemiplimab prior to surgery; cemiplimab and platinum doublet post surgery (NSCLC) Not open for accrual

Drug: cemiplimab; Drug: Platinum Doublet

Cohort A2

EXPERIMENTAL

Cemiplimab and platinum doublet prior to surgery; cemiplimab and platinum doublet post surgery (NSCLC) Not open for accrual

Drug: cemiplimab; Drug: Platinum Doublet

Cohort A3

EXPERIMENTAL

Platinum doublet prior to surgery; cemiplimab and platinum doublet post surgery (NSCLC) Not open for accrual

Drug: cemiplimab; Drug: Platinum Doublet

Cohort B

EXPERIMENTAL

Cemiplimab prior to surgery; cemiplimab post surgery (HCC)

Drug: cemiplimab

Cohort C

EXPERIMENTAL

Cemiplimab prior to surgery; standard of care radiation and/or chemotherapy followed by cemiplimab post surgery (HNSCC) Not open for accrual

Drug: cemiplimab

Cohort B2

EXPERIMENTAL

SBRT 8 Gy X 3 fractions followed by cemiplimab prior to surgery; cemiplimab post surgery (HCC)

Drug: cemiplimab

Cohort B3

EXPERIMENTAL

Cemiplimab and fianlimab before and after surgery (HCC)

Drug: cemiplimab; Drug: fianlimab

Interventions

cemiplimab DRUG

Administered intravenous (IV)

Also known as: REGN2810, Libtayo

Cohort A1; Cohort A2; Cohort A3; Cohort B; Cohort B2; Cohort B3; Cohort C

Platinum Doublet DRUG

Administered intravenous (IV)

Cohort A1; Cohort A2; Cohort A3

fianlimab DRUG

Administered IV

Also known as: REGN3767

Cohort B3

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Regeneron Pharmaceuticals: lead

Study Sites (1)

Icahn School of Medicine at Mount Sinai

New York, New York, 10029, United States

Location

Related Publications (1)

• 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.

  PMID: 35065058 DERIVED

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Carcinoma, Hepatocellular; Squamous Cell Carcinoma of Head and Neck

Interventions

cemiplimab

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Liver Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Liver Diseases; Carcinoma, Squamous Cell; Head and Neck Neoplasms

Study Officials

• Clinical Trial Management

  Regeneron Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: Cohorts B and C are not randomized
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 5, 2019
• First Posted: April 16, 2019
• Study Start: July 23, 2019
• Primary Completion: March 31, 2025
• Study Completion (Estimated): May 14, 2030
• Last Updated: April 11, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• 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.
• 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).

Locations

US (1)