Study of REGN2810 in Patients With Advanced Cutaneous Squamous Cell Carcinoma

Study Overview
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Brief Summary
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Groups 1 to 4 To estimate the clinical benefit of cemiplimab monotherapy for patients with: metastatic (nodal or distant) cutaneous squamous cell carcinoma (CSCC), or unresectable locally advanced CSCC Group 6 To provide additional efficacy and safety data for cemiplimab monotherapy in patients with advanced CSCC (metastatic [nodal or distant] or locally advanced treated with cemiplimab

Official Title
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A Phase 2 Study of REGN2810, a Fully Human Monoclonal Antibody to Programmed Death-1 (PD-1), in Patients With Advanced Cutaneous Squamous Cell Carcinoma

Conditions
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Advanced Cutaneous Squamous Cell Carcinoma

Intervention / Treatment
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* Drug: cemiplimab


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: At least 1 measurable lesion Eastern Cooperative Oncology Group (ECOG) performance status ≤1 Adequate bone marrow function Adequate renal function Adequate hepatic function Archived or newly obtained tumor material Patients must consent to undergo biopsies of CSCC lesions (Groups 2, 4, and 6) Surgical or radiological treatment of lesions contraindicated Key Exclusion Criteria: Ongoing or recent (within 5 years) evidence of significant autoimmune disease that required treatment with systemic immunosuppressive treatments, which may suggest risk for immune-related adverse events Prior treatment with an agent that blocks the PD-1/PD-L1pathway Prior treatment with a BRAF inhibitor Prior treatment with other immune-modulating agents within fewer than 4 weeks prior to the first dose of cemiplimab, or associated with immune-mediated adverse events that were ≥ grade 1 within 90 days prior to the first dose of cemiplimab, or associated with toxicity that resulted in discontinuation of the immune-modulating agent. Examples of immune-modulating agents include therapeutic vaccines, cytokine treatments, or agents that target cytotoxic T-lymphocyte antigen 4 (CTLA-4), 4-1BB (CD137), or OX-40. Untreated brain metastasis(es) that may be considered active Immunosuppressive corticosteroid doses (>10 mg prednisone daily or equivalent) within 4 weeks prior to the first dose of cemiplimab Infection with human immunodeficiency virus (HIV) and/or chronic/active infection with hepatitis B virus or hepatitis C virus History of non-infectious pneumonitis within the last 5 years Allergic reactions or acute hypersensitivity reaction attributed to antibody treatments Known allergy to doxycycline or tetracycline Patients with a history of solid organ transplant Any medical co-morbidity, physical examination finding, or metabolic dysfunction, or clinical laboratory abnormality that renders the patient unsuitable Other protocol-defined inclusion/exclusion criteria apply

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1<br>Patients with metastatic CSCC: to distant sites or lymph nodes. Cemiplimab administered intravenously (IV) every 2 weeks (Q2W). | Drug: cemiplimab<br> <br> * Other names: Libtayo;|
| Experimental: Group 2<br>Patients with unresectable locally advanced CSCC. Cemiplimab administered IV Q2 weeks. | Drug: cemiplimab<br> <br> * Other names: Libtayo;|
| Experimental: Group 3<br>Patients with metastatic CSCC to distant sites or lymph nodes. Cemiplimab administered IV Q3 weeks. | Drug: cemiplimab<br> <br> * Other names: Libtayo;|
| Experimental: Group 4<br>Patients with advanced CSCC [metastatic (nodal or distal) or unresectable locally advanced] Cemplimab administered IV Q4 weeks. | Drug: cemiplimab<br> <br> * Other names: Libtayo;|
| Experimental: Group 6<br>Patients with advanced CSCC (metastatic [nodal or distant] or locally advanced) who received cemiplimab IV Q3W for at least 27 weeks without experiencing disease progression, will have the option to receive cemiplimab by subcutaneous (SC) injection Q3W (first 12 patients) or Q6W (next ≥ 6 patients) basis. | Drug: cemiplimab<br> <br> * Other names: Libtayo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate (ORR) | Groups 1, 3, 4, and 6: Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 will be used to determine ORR. Group 2: Clinical response criteria will be used to determine ORR | 30 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Investigator Assessments of ORR | Groups 1-4, and 6 | Up to 30 months | 
| Duration of response | Groups 1-4, and 6 | Up to 30 months | 
| PFS (progression-free survival) | Groups 1-4, and 6 | Up to 30 months | 
| Overall Survival | Groups 1-4, and 6 | Up to 30 months | 
| Complete Response (CR) Rate | Groups 1-4, and 6 | Up to 30 months | 
| Change in scores of patient reported outcomes on EORTC QLQ-C30 | Except Group 6 | Up to 30 months | 
| Incidence of Treatment Emergent Adverse Events (TEAEs) |  | Up to 30 months | 
| Cemiplimab PK: Concentration at end-of-infusion (Ceoi) (IV) |  | Up to 24 months | 
| Cemiplimab PK: Peak concentrations (Cmax) (SC) |  | Up to 24 months | 
| Cemiplimab PK: Pre-infusion concentration (Ctrough) |  | Up to 24 months | 
| Cemiplimab PK: Time of end-of-infusion (teoi) |  | Up to 24 months | 
| Cemiplimab PK: Time to peak concentration (tmax) (SC) |  | Up to 24 months | 
| Cemiplimab PK: Area under the plasma concentration-time curve after the first SC or IV dose |  | Up to 24 months | 
| Cemiplimab PK: Absolute bioavailability after SC administration |  | Up to 24 months | 
| Anti-cemiplimab antibodies |  | Up to 30 months | 
| Immunohistochemistry (IHC) assessment of correlation between PD-L1 status and ORR | Group 6 | Up to 30 months | 
| IHC assessment of correlation between PD-L1 and DOR | Group 6 | Up to 30 months | 
| IHC assessment of correlation between PD-L1 and PFS | Group 6 | Up to 30 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Metastatic CSCC, Unresectable locally advanced CSCC