Advanced Cutaneous Squamous Cell Carcinoma, Cutaneous Squamous Cell Carcinoma, Metastatic Cutaneous Squamous Cell Carcinoma
Conditions
Keywords
Oncolytic Virus, Carcinoma, Carcinoma, Squamous Cell, Cemiplimab, Metastatic Cutaneous Squamous Cell Carcinoma, Oncolytic Immuno-gene therapy
Brief summary
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.
Detailed description
RP1 is a selectively replication competent herpes simplex virus type 1(HSV-1). This is a Phase 1/2, open-label, multicenter repeat-dosing study of RP1 alone and in combination with nivolumab in patients with advanced malignancies, and contains both single agent dose escalation, dose expansion to include nivolumab, and the combination in multiple Phase 2 cohorts in individual tumor types.
Interventions
DRUGCemiplimab
Cemiplimab administered intravenously
BIOLOGICALRP1
RP1 administered intratumorally
Sponsors
Regeneron Pharmaceuticals
Replimune Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
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/
Design outcomes
Primary
| Measure | 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
| Measure | Time frame |
|---|---|
| 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 |
| Progression Free Survival (PFS) by blinded independent review. | 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 |
| Overall Survival (OS) | up to 5 years |
| ORR/CRR by investigator assessment and blinded independent review | up to 5 years |
Countries
Australia, Bulgaria, Canada, France, Germany, Greece, Italy, Poland, Spain, United States
Outcome results
None listed