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

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.