Clinical Trials /

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

NCT03916627

Description:

The primary objective of the study is to evaluate the clinical activity of neoadjuvant cemiplimab therapy in patients with resectable Non-small cell lung cancer (NSCLC), Hepatocellular carcinoma (HCC), and Head and neck squamous cell carcinoma (HNSCC) lesions, as measured by pathological evaluations of resected tumors. The secondary objectives of the study are: - To assess the anti-tumor activity of neoadjuvant and adjuvant cemiplimab therapy as defined by multiple criteria - To determine the safety and tolerability of neoadjuvant and adjuvant cemiplimab therapy including delay to surgery - To assess the change in tumor-infiltrating CD8 T-cell density and to explore the correlation to the pathological response to therapy

Related Conditions:
  • Head and Neck Squamous Cell Carcinoma
  • Hepatocellular Carcinoma
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Neoadjuvant Cemiplimab for the Treatment of Resectable NSCLC, HCC, and HNSCC
  • Official Title: A Multi-Cohort Exploratory Study of Neoadjuvant Cemiplimab for the Treatment of Resectable NSCLC, HCC, and HNSCC

Clinical Trial IDs

  • ORG STUDY ID: R2810-ONC-1866
  • NCT ID: NCT03916627

Conditions

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

Interventions

DrugSynonymsArms
cemiplimabREGN2810, LibtayoCohort A1
Platinum DoubletCohort A1

Purpose

The primary objective of the study is to evaluate the clinical activity of neoadjuvant cemiplimab therapy in patients with resectable Non-small cell lung cancer (NSCLC), Hepatocellular carcinoma (HCC), and Head and neck squamous cell carcinoma (HNSCC) lesions, as measured by pathological evaluations of resected tumors. The secondary objectives of the study are: - To assess the anti-tumor activity of neoadjuvant and adjuvant cemiplimab therapy as defined by multiple criteria - To determine the safety and tolerability of neoadjuvant and adjuvant cemiplimab therapy including delay to surgery - To assess the change in tumor-infiltrating CD8 T-cell density and to explore the correlation to the pathological response to therapy

Trial Arms

NameTypeDescriptionInterventions
Cohort A1ExperimentalCemiplimab prior to surgery; cemiplimab and platinum doublet post surgery (NSCLC)
  • cemiplimab
  • Platinum Doublet
Cohort A2ExperimentalCemiplimab and platinum doublet prior to surgery; cemiplimab and platinum doublet post surgery (NSCLC)
  • cemiplimab
  • Platinum Doublet
Cohort A3ExperimentalPlatinum doublet prior to surgery; cemiplimab and platinum doublet post surgery (NSCLC)
  • cemiplimab
  • Platinum Doublet
Cohort BExperimentalCemiplimab prior to surgery; cemiplimab post surgery (HCC)
  • cemiplimab
Cohort CExperimentalCemiplimab prior to surgery; standard of care radiation and/or chemotherapy followed by cemiplimab post surgery (HNSCC)
  • cemiplimab

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 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

        Note: Other protocol defined Inclusion/Exclusion criteria apply
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Major pathologic response (MPR) at time of surgery for the NSCLC cohorts
Time Frame:At time of surgery
Safety Issue:
Description:Cohorts A1, A2, A3

Secondary Outcome Measures

Measure:Delay to surgery
Time Frame:Surgery >28 days following last dose of cemiplimab
Safety Issue:
Description:As defined by surgery >28 days following last dose of cemiplimab in neoadjuvant period
Measure:Disease-free survival (DFS)
Time Frame:Up to 60 months
Safety Issue:
Description:Defined as the time from date of surgery until recurrence of tumor or death from any cause
Measure:Overall response rate (ORR)
Time Frame:At time of surgery
Safety Issue:
Description:Defined as the percent of patients with a complete response (CR) or partial response (PR) documented by the Investigator per modified RECIST 1.1.
Measure:Overall survival (OS)
Time Frame:Up to 60 months
Safety Issue:
Description:Defined as the time from the first dosing of cemiplimab (chemotherapy for Cohort A3) and date of death for any reason
Measure:OS rate
Time Frame:12 months
Safety Issue:
Description:
Measure:OS rate
Time Frame:18 months
Safety Issue:
Description:
Measure:OS rate
Time Frame:24 months
Safety Issue:
Description:
Measure:OS rate
Time Frame:36 months
Safety Issue:
Description:
Measure:OS rate
Time Frame:48 months
Safety Issue:
Description:
Measure:OS rate
Time Frame:60 months
Safety Issue:
Description:
Measure:Incidence of treatment emergent adverse events (TEAEs)
Time Frame:90 days post last dose of cemiplimab
Safety Issue:
Description:Grade 3 or higher per Common Terminology Criteria for Adverse Events (CTCAE V5.0)
Measure:Incidence of irAEs
Time Frame:90 days post last dose of cemiplimab
Safety Issue:
Description:Grade 3 or higher per Common Terminology Criteria for Adverse Events (CTCAE V5.0)
Measure:Incidence of SAEs
Time Frame:90 days post last dose of cemiplimab
Safety Issue:
Description:Grade 3 or higher per Common Terminology Criteria for Adverse Events (CTCAE V5.0)
Measure:Incidence of deaths
Time Frame:90 days post last dose of cemiplimab
Safety Issue:
Description:
Measure:Incidence of laboratory abnormalities
Time Frame:90 days post last dose of cemiplimab
Safety Issue:
Description:Grade 3 or higher per Common Terminology Criteria for Adverse Events (CTCAE V5.0)
Measure:Change in tumor-infiltrating CD8 T-cell density
Time Frame:Baseline to time of surgery
Safety Issue:
Description:Defined as the change from baseline to the time of surgery

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Regeneron Pharmaceuticals

Trial Keywords

  • NSCLC
  • HCC
  • HNSCC
  • Resectable

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