Intralesional Cemiplimab for Adult Patients With Cutaneous Squamous Cell Carcinoma or Basal Cell Carcinoma

Study Overview
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Brief Summary
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This study is researching an experimental drug called cemiplimab. The study is focused on Cutaneous Squamous Cell Carcinoma (CSCC) and Basal Cell Carcinoma (BCC). The aim of the study is to evaluate the safety and tolerability (how your body reacts to the drug) of cemiplimab (also known as REGN2810). The first part of the study tested several different doses of cemiplimab given weekly for 12 weeks. The study is also looking at several other research questions, including: What side effects may happen from taking the study drug To see effect of cemiplimab on your tumor How much study drug is in your blood at different times

Official Title
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A Phase 1 Study of Pre-Operative Cemiplimab (REGN2810), Administered Intralesionally, for Patients With Cutaneous Squamous Cell Carcinoma (CSCC) or Basal Cell Carcinoma (BCC)

Conditions
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Cutaneous Squamous Cell Carcinoma, Basal 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 Dose Escalation: History of recurrent resectable CSCC or BCC (Cohort C only) that satisfies conditions as defined in the protocol Patients must have measurable disease in the index lesion, defined as 1-2 cm in the longest diameter Eastern Cooperative Oncology Group (ECOG) performance status ≤1 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-mediated adverse events (imAEs) Prior treatment with an agent that blocks the programmed cell death 1 (PD-1)/ programmed cell death 1 ligand (PD-L1) pathway. Prior treatment with other systemic immune modulating agent as defined in the protocol M1 or N1, N2 (a, b, or c), or N3 CSCC or BCC. Patients with history of metastatic CSCC (distant or nodal), or metastatic BCC (distant or nodal) are excluded unless the disease-free interval is at least 3 years Concurrent malignancies, other than those with negligible risk of metastasis or death. Patients with hematologic malignancies, including chronic lymphocytic leukemia (CLL), are excluded. Patients with a history of solid organ transplant Has received a Coronavirus induced disease of 2019 (COVID-19) vaccination (initial series and booster) within 1 week of planned start of study medication Note: 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
Intervention Model: Single Group Assignment
Interventional Model Description: Cohorts A, B, D-G will enroll sequentially (not randomized). Cohort C for BCC will enroll in parallel with, and independently of, Cohorts A and B, D-G for CSCC patients
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cemiplimab<br>Three dose cohorts are planned and will follow a 3 + 3 dose-escalation design with cohort expansion. After completion of the above, three additional cohorts (A, B and C) of patients will be evaluated. Cohorts D, E, F, G may open after completion of Cohort B. | Drug: Cemiplimab<br>* Each patient will receive intralesional injections of cemiplimab every week (QW), or at less frequent dosing into the lesion at the assigned dose level for 5-12 weeks prior to scheduled surgery<br>* Other names: Libtayo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence, nature, and severity of dose limiting toxicities (DLTs) (if any) graded according to the National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI CTCAE) v5 | Dose levels 1-3 | From the first dose through day 28 | 
| Incidence, nature, and severity of treatment-emergent adverse events (TEAEs) graded according to the National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI CTCAE) v5 | Dose levels 1-3 | From the first dose to 90 days after the last dose | 
| Incidence and severity of TEAEs graded according to the NCI CTCAE v5 | Dose levels 1-3 and cohorts A - G | From the first dose up to 90 days after the last dose | 
| The incidence and severity of injection site reactions (ISRs) | Dose levels 1-3 and cohorts A - G | From the first dose to 90 days after the last dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate (ORR) | Determined by the investigator using the modified World Health Organization (WHO) criteria | At week 7; prior to week 13 surgery | 
| Pathologic complete response rate (or end of treatment biopsies, for patients who decline surgery) |  | At time of surgery | 
| Major pathologic response rate (or end of treatment biopsies, for patients who decline surgery) |  | At time of surgery | 
| Cemiplimab concentration in serum over time |  | From the first dose up to 90 days after the last dose | 
| Incidence of anti-drug antibody (ADA) titers for cemiplimab |  | Up to 90 days after last dose | 
| Selection of the recommended dose of cemiplimab for further study based on clinical and pharmacokinetic (PK) observations | The determination of the phase 2 recommended dose will be based primarily on clinical safety observations, according to the dose escalation scheme. | Up to 90 days after last dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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BCC, CSCC