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

• ClinicalTrials.gov Identifier: NCT03916627
• Recruitment Status: Recruiting
• First Posted: April 16, 2019
• Last Update Posted: December 2, 2020
• Sponsor: Regeneron Pharmaceuticals
• Collaborator: Sanofi
• Information provided by (Responsible Party): Regeneron Pharmaceuticals

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 (Clinical Trial)
• Estimated Enrollment: 94 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: July 23, 2019
• Estimated Primary Completion Date: June 20, 2022
• Estimated Study Completion Date: August 7, 2027

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)	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)	Drug: cemiplimab; Administered intravenous (IV); Other Names: REGN2810; Libtayo

Outcome Measures

Primary Outcome Measures :

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

Secondary Outcome Measures :

1. Delay to surgery [ Time Frame: 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
2. Disease-free survival (DFS) [ Time Frame: Up to 60 months ]
   Defined as the time from date of surgery until recurrence of tumor or death from any cause after successful surgery and recovery
3. Overall response rate (ORR) [ Time Frame: At time of surgery ]
   Defined as the percent of patients with a complete response (CR) or partial response (PR) documented by the Investigator per modified RECIST 1.1.
4. Overall survival (OS) [ Time Frame: Up to 60 months ]
   Defined as the time from the first dosing of cemiplimab (chemotherapy for cohort A3) and date of death for any reason
5. OS rate [ Time Frame: 12 months ]
6. OS rate [ Time Frame: 18 months ]
7. OS rate [ Time Frame: 24 months ]
8. OS rate [ Time Frame: 36 months ]
9. OS rate [ Time Frame: 48 months ]
10. OS rate [ Time Frame: 60 months ]
11. Incidence of treatment emergent adverse events (TEAEs) [ Time Frame: 90 days post last dose of cemiplimab ]
    Grade 3 or higher per Common Terminology Criteria for Adverse Events (CTCAE V5.0)
12. Incidence of irAEs [ Time Frame: 90 days post last dose of cemiplimab ]
    Grade 3 or higher per Common Terminology Criteria for Adverse Events (CTCAE V5.0)
13. Incidence of SAEs [ Time Frame: 90 days post last dose of cemiplimab ]
    Grade 3 or higher per Common Terminology Criteria for Adverse Events (CTCAE V5.0)
14. Incidence of deaths [ Time Frame: 90 days post last dose of cemiplimab ]
15. Incidence of laboratory abnormalities [ Time Frame: 90 days post last dose of cemiplimab ]
    Grade 3 or higher per Common Terminology Criteria for Adverse Events (CTCAE V5.0)
16. Change in tumor-infiltrating CD8 T-cell density [ Time Frame: Baseline to time of surgery ]
    Defined as the change from baseline to the time of surgery

Eligibility Criteria

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

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

Contacts and Locations

Contacts

Contact: Clinical Trials Administrator; 844-734-6643; clinicaltrials@regeneron.com

Locations

United States, New York

Icahn School of Medicine at Mount Sinai; Recruiting

New York, New York, United States, 10029

Contact 212-824-9472

Sponsors and Collaborators

Regeneron Pharmaceuticals

Sanofi

Investigators

• Study Director: Clinical Trial Management; Regeneron Pharmaceuticals

More Information

• Responsible Party: Regeneron Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT03916627
• Other Study ID Numbers: R2810-ONC-1866
• First Posted: April 16, 2019
• Last Update Posted: December 2, 2020
• Last Verified: November 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: All Individual Patient Data (IPD) that underlie publicly available results will be considered for sharing
• Supporting Materials: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (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).
• URL: https://vivli.org/

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Regeneron Pharmaceuticals:

NSCLC; HCC; HNSCC; Resectable

Additional relevant MeSH terms:

Cemiplimab; Carcinoma; Carcinoma, Hepatocellular; Squamous Cell Carcinoma of Head and Neck; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Carcinoma, Squamous Cell; Adenocarcinoma; Liver Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Liver Diseases; Head and Neck Neoplasms; Antineoplastic Agents, Immunological; Antineoplastic Agents