Study of RP1 Monotherapy and RP1 in Combination With Nivolumab

Inclusion Criteria:

1. Have an Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1.
2. At least one measurable and injectable lesion
3. Have provided a former tumor pathology specimen or be willing to supply a new tumor sample from a biopsy
4. Have a predicted life expectancy of ≥ 3 months
5. Measurable disease, according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria
6. Subjects with MSI-H or dMMR tumors: has diagnosis of MSI-H or metatstatic dMMR tumor (according to protocol definition) who has progressed on prior anti-PD1/PD-L1 therapy.
7. Subjects with NMSC: has diagnosis of locally advanced or metastatic NMSC that are not considered treatable by surgery including basal cell carcinoma, cutaneous squamous cell carcinoma, basosquamous carcinoma, Merkel cell carcinoma and other non-melanoma skin cancers (per protocol). Patients must have received 8 weeks of anti-PD1/PD-L1 as their last line of therapy and progressed while on treatment.
8. Subjects with anti-PD1 failed cutaneous melanoma: has confirmed progressive disease while on anti-PD1 treatment for at least 8 weeks and documented BRAF mutation status
9. Subjects with anti-PD1 failed NSCLC: must have failed prior treatment, including PD1/PD-L1 directed therapy administered either as monotherapy or in combination with platinum-based chemotherapy or anti-CTLA-4. The most recent treatment given must have included an anti-PD1/PD-L1 directed therapy with radiologic disease progression on or after treatment.

Exclusion Criteria:

1. Prior treatment with an oncolytic therapy
2. History of viral infections according to the protocol
3. Prior complications with herpes infections
4. Chronic use of anti-virals
5. Uncontrolled/untreated brain metastasis
6. History of interstitial lung disease
7. History of non-infectious pneumonitis
8. History of clinically significant cardiovascular disease