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

Primary Purpose

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

Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
cemiplimab
Platinum Doublet
fianlimab
Sponsored by
Regeneron Pharmaceuticals
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Non-small Cell Lung Cancer focused on measuring NSCLC, HCC, HNSCC, Resectable

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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 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 EGFR gene mutations, ALK gene translocations, or ROS1 fusions.

Note: Other protocol defined Inclusion/Exclusion criteria apply

Sites / Locations

  • Icahn School of Medicine at Mount SinaiRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm Type

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Arm Label

Cohort A1

Cohort A2

Cohort A3

Cohort B

Cohort C

Cohort B2

Cohort B3

Arm Description

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

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

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

Cemiplimab prior to surgery; cemiplimab post surgery (HCC)

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

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

Cemiplimab and fianlimab before and after surgery (HCC)

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Delay to surgery
Defined as surgery >28 days following the end of the second cycle of cohort specific neoadjuvant therapy
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.
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
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
Overall survival (OS)
Defined as the time from the first study treatment and date of death for any reason
OS rate
OS rate
OS rate
OS rate
OS rate
OS rate
Incidence of treatment emergent adverse events (TEAEs)
Grade 3 or higher per Common Terminology Criteria for Adverse Events (CTCAE V5.0)
Incidence of imAEs
Grade 3 or higher per Common Terminology Criteria for Adverse Events (CTCAE V5.0)
Incidence of SAEs
Grade 3 or higher per Common Terminology Criteria for Adverse Events (CTCAE V5.0)
Incidence of deaths
Incidence of laboratory abnormalities
Grade 3 or higher per Common Terminology Criteria for Adverse Events (CTCAE V5.0)
Change in tumor-infiltrating CD8 T-cell density
Defined as the change from baseline to the time of surgery

Full Information

First Posted
April 5, 2019
Last Updated
May 26, 2023
Sponsor
Regeneron Pharmaceuticals
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1. Study Identification

Unique Protocol Identification Number
NCT03916627
Brief Title
Neoadjuvant Cemiplimab for the Treatment of Resectable NSCLC, HCC, and HNSCC in Adult Patients
Official Title
A Multi-Cohort Exploratory Study of Neoadjuvant Cemiplimab for the Treatment of Resectable NSCLC, HCC, and HNSCC
Study Type
Interventional

2. Study Status

Record Verification Date
May 2023
Overall Recruitment Status
Recruiting
Study Start Date
July 23, 2019 (Actual)
Primary Completion Date
April 22, 2025 (Anticipated)
Study Completion Date
February 26, 2031 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Regeneron Pharmaceuticals

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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)

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Non-small Cell Lung Cancer, Hepatocellular Carcinoma, Head and Neck Squamous Cell Carcinoma
Keywords
NSCLC, HCC, HNSCC, Resectable

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Masking Description
Cohorts B and C are not randomized
Allocation
Randomized
Enrollment
73 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Cohort A1
Arm Type
Experimental
Arm Description
Cemiplimab prior to surgery; cemiplimab and platinum doublet post surgery (NSCLC) Not open for accrual
Arm Title
Cohort A2
Arm Type
Experimental
Arm Description
Cemiplimab and platinum doublet prior to surgery; cemiplimab and platinum doublet post surgery (NSCLC) Not open for accrual
Arm Title
Cohort A3
Arm Type
Experimental
Arm Description
Platinum doublet prior to surgery; cemiplimab and platinum doublet post surgery (NSCLC) Not open for accrual
Arm Title
Cohort B
Arm Type
Experimental
Arm Description
Cemiplimab prior to surgery; cemiplimab post surgery (HCC)
Arm Title
Cohort C
Arm Type
Experimental
Arm Description
Cemiplimab prior to surgery; standard of care radiation and/or chemotherapy followed by cemiplimab post surgery (HNSCC) Not open for accrual
Arm Title
Cohort B2
Arm Type
Experimental
Arm Description
SBRT 8 Gy X 3 fractions followed by cemiplimab prior to surgery; cemiplimab post surgery (HCC)
Arm Title
Cohort B3
Arm Type
Experimental
Arm Description
Cemiplimab and fianlimab before and after surgery (HCC)
Intervention Type
Drug
Intervention Name(s)
cemiplimab
Other Intervention Name(s)
REGN2810, Libtayo
Intervention Description
Administered intravenous (IV)
Intervention Type
Drug
Intervention Name(s)
Platinum Doublet
Intervention Description
Administered intravenous (IV)
Intervention Type
Drug
Intervention Name(s)
fianlimab
Other Intervention Name(s)
REGN3767
Intervention Description
Administered IV
Primary Outcome Measure Information:
Title
Major pathologic response (MPR) at time of surgery for the NSCLC cohorts
Description
Cohorts A1, A2, A3
Time Frame
At time of surgery
Title
Significant tumor necrosis (STN) at time of surgery is the primary endpoint for the HCC cohorts
Description
Cohort B, B2, B3
Time Frame
At time of surgery
Title
Major treatment effect (MTE) at time of surgery is the primary endpoint for the HNSCC cohort
Description
Cohort C
Time Frame
At time of surgery
Secondary Outcome Measure Information:
Title
Delay to surgery
Description
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
Title
Event-free survival (EFS)
Description
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
Title
Disease-free survival (DFS)
Description
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
Title
Overall response rate (ORR)
Description
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
Title
Overall survival (OS)
Description
Defined as the time from the first study treatment and date of death for any reason
Time Frame
Up to 60 months following surgery
Title
OS rate
Time Frame
12 months
Title
OS rate
Time Frame
18 months
Title
OS rate
Time Frame
24 months
Title
OS rate
Time Frame
36 months
Title
OS rate
Time Frame
48 months
Title
OS rate
Time Frame
60 months
Title
Incidence of treatment emergent adverse events (TEAEs)
Description
Grade 3 or higher per Common Terminology Criteria for Adverse Events (CTCAE V5.0)
Time Frame
Up to 60 months following surgery
Title
Incidence of imAEs
Description
Grade 3 or higher per Common Terminology Criteria for Adverse Events (CTCAE V5.0)
Time Frame
Up to 60 months following surgery
Title
Incidence of SAEs
Description
Grade 3 or higher per Common Terminology Criteria for Adverse Events (CTCAE V5.0)
Time Frame
Up to 60 months following surgery
Title
Incidence of deaths
Time Frame
Up to 60 months following surgery
Title
Incidence of laboratory abnormalities
Description
Grade 3 or higher per Common Terminology Criteria for Adverse Events (CTCAE V5.0)
Time Frame
Up to 60 months following surgery
Title
Change in tumor-infiltrating CD8 T-cell density
Description
Defined as the change from baseline to the time of surgery
Time Frame
Baseline to time of surgery

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Clinical Trials Administrator
Phone
844-734-6643
Email
clinicaltrials@regeneron.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Trial Management
Organizational Affiliation
Regeneron Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
Icahn School of Medicine at Mount Sinai
City
New York
State/Province
New York
ZIP/Postal Code
10029
Country
United States
Individual Site Status
Recruiting
Facility Contact:
Phone
212-824-9472

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing 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 URL
https://vivli.org/
Citations:
PubMed Identifier
35065058
Citation
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.
Results Reference
derived

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

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