Study Evaluating Cemiplimab Alone and Combined With RP1 in Treating Advanced Squamous Skin Cancer

Study Overview
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Brief Summary
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To estimate the clinical benefit of cemiplimab monotherapy versus cemiplimab in combination with RP1 for patients with locally advanced or metastatic CSCC, as assessed by overall response rate (ORR) and complete response rate (CRR) according to blinded independent review.

Official Title
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A Randomized, Controlled, Open-Label, Phase 2 Study of Cemiplimab as a Single Agent and in Combination With RP1 in Patients With Advanced Cutaneous Squamous Cell Carcinoma

Conditions
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Cutaneous Squamous Cell Carcinoma, Advanced Cutaneous Squamous Cell Carcinoma, Metastatic Cutaneous Squamous Cell Carcinoma

Intervention / Treatment
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* Drug: Cemiplimab
* Biological: RP1


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Histologically confirmed locally advanced or metastatic cutaneous squamous cell carcinoma Patients with locally advanced disease who are not suitable candidates for surgical or radiological treatment of lesions or have refused those treatments At least 1 lesion that is measurable and injectable by study criteria Eastern Cooperative Oncology Group (ECOG) performance status ≤1. Patients with ECOG PS 2 at baseline may be allowed to enroll if PS 2 status is only related to the CSCC disease under study Anticipated life expectancy >12 weeks All patients must consent to provide archived or newly obtained tumor material for central pathology review for confirmation of diagnosis of CSCC. Key Exclusion Criteria: Prior treatment with an oncolytic therapy Patients with active significant herpetic infections or prior complications of HSV-1 infection (e.g. herpetic keratitis or encephalitis) Patients who require intermittent or chronic use of systemic (oral or intravenous) anti-virals with known anti-herpetic activity (e.g. acyclovir) Ongoing or recent (within 5 years) evidence of significant autoimmune disease that required treatment with systemic immunosuppressive treatments Prior treatment with an agent that blocks the PD-1/PD-L1 pathway. Prior treatment with other immune modulating agents other than as adjuvant or neoadjuvant therapy within 3 years. Untreated brain metastasis(es) that may be considered active. Acute or chronic active hepatitis B or known history of hepatitis B or hepatitis C or human immunodeficiency virus (HIV) infection History of ILD/pneumonitis within the last 5 years or a history of ILD/pneumonitis requiring treatment with systemic steroids. Any major or surgical procedure ≤ 28 days before randomization Administration of live vaccines ≤ 28 days before randomization 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cemiplimab in combination with RP1<br>Cemiplimab administered intravenously every 3 weeks in combination with RP1 administered as an intratumoral injection every 3 weeks | Drug: Cemiplimab<br>* Cemiplimab administered intravenously<br>* Other names: Libtayo;Biological: RP1<br>* RP1 administered intratumorally<br>* Other names: Genetically modified herpes simplex type 1 virus;|
| Active Comparator: Cemiplimab<br>Cemiplimab administered intravenously as a single therapy every 3 weeks | Drug: Cemiplimab<br>* Cemiplimab administered intravenously<br>* Other names: Libtayo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (ORR) according to blinded independent review |  | up to 5 years | 
| Complete Response Rate (CRR) according to blinded independent review |  | up to 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival (PFS) by blinded independent review. |  | up to 5 years | 
| ORR/CRR by investigator assessment and blinded independent review |  | up to 5 years | 
| ORR/CRR for patients with metastatic or locally advanced disease according to investigator review and blinded independent review |  | up to 5 years | 
| ORR/CRR for patients who have and have not previously received systemic CSCC-directed therapy and blinded independent review |  | up to 5 years | 
| Duration of Response (DOR) per investigator review and blinded independent review |  | up to 5 years | 
| Progression-free Survival (PFS) per investigator review |  | up to 5 years | 
| Overall Survival (OS) |  | up to 5 years | 
| 3-year survival |  | 3 years | 
| Change in overall scores of patient-reported outcomes in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) |  | approximately 30 months | 
| Evaluation of the safety and tolerability of cemiplimab alone and combined with RP1 as assessed via adverse events (AEs) |  | approximately 26 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Oncolytic Virus, Carcinoma, Carcinoma, Squamous Cell, Cemiplimab, Metastatic Cutaneous Squamous Cell Carcinoma, Oncolytic Immuno-gene therapy