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

Sponsor

Regeneron Pharmaceuticals (Industry)

Overall Status

Recruiting

CT.gov ID

NCT03916627

Collaborator

Sanofi (Industry)

Enrollment

Location

Arms

121.4

Anticipated Duration (Months)

0.7

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Non-small Cell Lung Cancer Hepatocellular Carcinoma Head and Neck Squamous Cell Carcinoma	Drug: cemiplimab Drug: Platinum Doublet	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

88 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Masking Description:

Cohorts B and C are not randomized

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Jul 23, 2019

Anticipated Primary Completion Date :

Jul 15, 2024

Anticipated Study Completion Date :

Sep 3, 2029

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cohort A1 Cemiplimab prior to surgery; cemiplimab and platinum doublet post surgery (NSCLC)	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)	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) No longer enrolling	Drug: cemiplimab Administered intravenous (IV) Other Names: REGN2810 Libtayo Drug: Platinum Doublet Administered intravenous (IV)
Experimental: Cohort B Cemiplimab prior to surgery; cemiplimab post surgery (HCC)	Drug: cemiplimab Administered intravenous (IV) Other Names: REGN2810 Libtayo
Experimental: Cohort C Cemiplimab prior to surgery; standard of care radiation and/or chemotherapy followed by cemiplimab post surgery (HNSCC) No longer enrolling	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

Outcome Measures

Primary Outcome Measures

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

Secondary Outcome Measures

Delay to surgery [Surgery >28 days following the end of the cycle of last dose of cemiplimab]
Defined as surgery >28 days following the end of the cycle of last dose of cemiplimab in neoadjuvant period
Event-free survival (EFS) [Up to 60 months following surgery]
Defined as the time from the first dosing of cemiplimab (SBRT for cohort B2) 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) [Up to 60 months following surgery]
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) [Up to 60 months following surgery]
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) [Up to 60 months following surgery]
Defined as the time from the first dosing of cemiplimab (chemotherapy for cohort A3 and SBRT for cohort B2) and date of death for any reason
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) [Up to 60 months following surgery]
Grade 3 or higher per Common Terminology Criteria for Adverse Events (CTCAE V5.0)
Incidence of irAEs [Up to 60 months following surgery]
Grade 3 or higher per Common Terminology Criteria for Adverse Events (CTCAE V5.0)
Incidence of SAEs [Up to 60 months following surgery]
Grade 3 or higher per Common Terminology Criteria for Adverse Events (CTCAE V5.0)
Incidence of deaths [Up to 60 months following surgery]
Incidence of laboratory abnormalities [Up to 60 months following surgery]
Grade 3 or higher per Common Terminology Criteria for Adverse Events (CTCAE V5.0)
Change in tumor-infiltrating CD8 T-cell density [Baseline to time of surgery]
Defined as the change from baseline to the time of surgery

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts 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.