This is a Phase 1b, single-center, open-label study, evaluating efficacy and safety of RP1 for the treatment of resectable cutaneous Squamous Cell Carcinoma in up to 12 evaluable patients. In this study, patients will receive RP1 via direct intratumoral (IT) injection into superficial cutaneous solid tumors to assess the safety and tolerability as well efficacy of RP1 treatment. The primary efficacy population is up to 12 evaluable patients with resectable CSCC. The enrollment of patients with CSCC will determine study duration.

Inclusion Criteria:

• Voluntary agreement to provide written informed consent prior to any study procedures and the willingness and ability to comply with all aspects of the protocol.
• Male or female ≥ 18 years of age on the day of signed informed consent.
• Patients must be treatment naïve in the target lesion(s).
• Patients for whom surgical treatment of lesions is clinically indicated.
• At least one measurable histologically confirmed cutaneous tumor of ≥ 1.0 cm in longest diameter and ≤ 3.0 cm with clinically visible residual tumor. More than one tumor may be treated including newly diagnosed lesions.
• ECOG performance status ≤ 1.
• Adequate hepatic function, including both of the following:
• Adequate hematologic function
• Adequate coagulation parameters, including both of the following:
• Anticipated life expectancy > 2 years
• Have provided either formalin-fixed, paraffin-embedded (FFPE) tissue block or unstained tumor tissue sections, obtained within four months prior to enrollment, with an associated pathology report,. Biopsy can be either by punch or shave method.. A fresh biopsy is required at screening if an archival biopsy (within four months prior to enrollment) is not available.

Exclusion Criteria:

• Prior treatment with an oncolytic therapy or intratumoral immunotherapy (e.g. TLR agonists, etc.).
• Patients with known visceral metastases.
• 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 IV) antiviral agents with known antiherpetic activity (e.g., acyclovir, valacyclovir, famciclovir, ganciclovir, valganciclovir). Note: Patients with sporadic cold sores may be enrolled as long as no active cold sores are present at the time of first dose of RP1.
• Had systemic infection requiring IV antibiotics or other serious infection within 14 days prior to dosing.
• Patients with an active, known, or suspected autoimmune disease that requires systemic immunosuppressive treatment. Patients with vitiligo, childhood asthma that has resolved, type 1 diabetes mellitus, hypothyroidism only requiring hormone replacement, or psoriasis that does not require systemic treatment are permitted to enroll.
• Patients with a history of any positive test result for hepatitis B virus (HBV) or hepatitis C virus (HCV) indicating the presence of the virus, e.g., hepatitis B surface antigen [HBsAg] positive or hepatitis C antibody (anti-HCV) positive (except if HCV RNA negative), or human immunodeficiency virus (HIV) positive. Patients with a history of HBV or HCV infection must have undetectable viral load within three months of study entry. (Note: No testing for HBV, HCV, or HIV is required unless mandated by local health authorities).
• Had clinically significant cardiovascular disease within 6 months from first dose of study drug, including New York Heart Association Class III or IV congestive heart failure, unstable angina, myocardial infarction or stroke/transient ischemic attack or significant cardiac arrhythmias associated with hemodynamic instability.
• Radiation therapy within 14 days of first dose of RP1, or topical therapy within 30 days of RP1, is not allowed. The patient must have recovered from all AEs due to previous therapies to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE version 5.0) Grade 1 or baseline. Participants with unresolved radiation-induced xerostomia are eligible.
• Documented history of allergic reactions or acute hypersensitivity reaction attributed to RP1 or to any of the excipients.
• Patients with solid organ transplantation
• Tumors for which margins are not well defined, either clinically or based on pathologic report (Ill-defined tumors).
• Tumors where invasion beyond the subcutaneous fat is suspected
• Any co-morbidity, physical examination finding, metabolic dysfunction, or clinical laboratory abnormality that, in the opinion of the investigator, renders the patient unsuitable for participation due to safety risks and/or potential to affect interpretation of results of the study.
• Treatment with botanical preparations (e.g., herbal supplements or traditional Chinese medicines) intended for general health support or to treat the disease under study within two weeks prior to the first dose of RP1 and throughout the study as per Section 5.10.2.
• Any active malignancy within three years of the date of first planned dose of RP1, except for the specific cancer under investigation in this study and tumors with negligible risk of metastasis or death, squamous cell carcinoma in situ (SCCIS), basal cell carcinoma (BCC) or other small CSSS, melanoma in situ, carcinoma in situ of the cervix, ductal carcinoma in situ of the breast, low-risk early stage prostate adenocarcinoma (T1T2aN0M0), Gleason score ≤ 6, and prostate specific antigen (PSA) ≤ 10 ng/mL) for which the management plan is active surveillance, or prostate adenocarcinoma with biochemical-only recurrence with documented PSA doubling time of > 12 months for which the management plan is active surveillance. Patients with hematologic malignancies are excluded, except for patients with chronic lymphocytic leukemia (CLL) who are considered stable and not on active treatment.
• Any acute or chronic psychiatric problems, alcohol abuse, or substance abuse disorders that, in the opinion of the investigator, would interfere with the patient's ability to comply with the requirements of the study.