This is a Phase 1, multicenter, open label, single agent dose escalation and combination treatment study of RP3 in adult participants with advanced solid tumors, to evaluate the safety and tolerability of RP3 both as a single agent and in combination with anti-PD1 therapy and to determine the recommended Phase 2 dose (RP2D) of RP3.

RP3 is a genetically modified herpes simplex type 1 virus (HSV-1) that expresses exogenous genes (anti-CTLA-4 antibody, CD40 ligand and h4-1BBL) designed to directly destroy tumors and generate an anti-tumor immune response

Inclusion Criteria:

• Patients with advanced or metastatic non-neurological solid tumors, who have progressed on standard therapy or cannot tolerate standard therapy, or for whom there is no standard therapy preferred to enrollment in a clinical study
• All patients must consent to provide archival tumor biopsy samples within 12 months, or a fresh tumor biopsy is needed. Patients must also consent to provide on treatment biopsies as per protocol
• At least one measurable tumor ≥ 1 cm in longest diameter (or shortest diameter for lymph nodes)
• At least one injectable tumor ≥ 1 cm in longest diameter or injectable tumors which in aggregate are ≥ 1 cm in longest diameter (or shortest diameter for lymph nodes
• Have an Eastern Cooperative Oncology Group (ECOG) performance status 0-1

Note: Predefined inclusion criteria may apply for each additional expansion cohort.

Exclusion Criteria:

• Prior treatment with an oncolytic virus therapy

• History of viral infections according to the protocol

• Systemic infection requiring intravenous (IV) antibiotics

• Active significant herpetic infections or prior complications of HSV-1 infection (e.g., herpetic keratitis or encephalitis)

• Requires intermittent or chronic use of systemic antivirals

  a. Hepatocellular carcinoma patients with a diagnosis of hepatitis B must be off antiviral therapy for at least 4 weeks prior to enrollment . Hepatocellular carcinoma patients with a history of or ongoing hepatitis C infection must have completed treatment for hepatitis C at least 1 month prior to study enrollment and hepatitis

• History of interstitial lung disease

• Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis

Additional Exclusion Criteria for Patients Enrolled in Part 2 (Expansion Cohorts):

• History of life-threatening toxicity related to prior immune treatment or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways
• Treatment with botanical preparations within 2 weeks prior to treatment.
• Active, known, or suspected autoimmune disease requiring systemic treatment.
• History of interstitial lung disease.
• Severe hypersensitivity to another monoclonal antibody.
• Has received prior radiotherapy within 2 weeks of start of study treatment.
• Has received a live vaccine within 28 days prior to the first dose of study treatment.
• History of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
• History of myocarditis or congestive heart failure within 6 months of screening.
• Has a serious or uncontrolled medical disorder.
• Has a QT interval corrected for heart rate using Fridericia's formula (QTcF) > 480 msec, except for right bundle branch block.