Inclusion Criteria:  Histological or cytological diagnosis of locally advanced or metastatic solid tumors known to have approved therapies using immune checkpoint inhibitors or anti-vascular endothelial growth factor agents Have exhausted (or refuse) all available standard of care therapy (e.g., including anti-PD1/programmed death ligand 1 [PDL1] if applicable) or for whom no standard therapy is available for their tumor type Patients with prior anti-PD1/PDL1 must have documentation of primary or secondary resistance to last prior anti-PD1/PDL1 therapy according to Immunotherapy Resistance Committee (SITC) (Kluger et al, 2020) Have at least 1 measurable lesion by RECIST 1.1 that has not been previously irradiated (for Part 2 only) Have recently obtained archival tumor tissue sample available, or undergo de novo tumor biopsy Eastern Cooperative Oncology Group (ECOG) PS 0-1 Adequate hematologic, renal, and liver functions Dose Escalation (Part 1A and 1B): Any advanced or metastatic solid tumor fulfilling other relevant eligibility criteria. Dose Expansion (Part 2): Tumor specific cohorts (NSCLC, RCC, melanoma, MSS CRC) must have received prior approved therapies (Part 2)  Exclusion Criteria:  Other active malignancy Recent major surgery Systemic anticancer therapy and chemotherapy within protocol-defined washout period Known or suspected hypersensitivity to prior treatment with any vaccinia oncolytic, pox virus, or antiviral agents within the past 10 years Current or history of myocarditis or congestive heart failure (New York Heart Association [NYHA] III-IV); unstable angina; or serious uncontrolled arrhythmia or recent myocardial infarction Active or history of interstitial lung disease (ILD)/pneumonitis Patients requiring chronic systemic immunosuppressants History of severe immune mediated side effect that was considered related to prior immune modulatory therapy and requiring immunosuppressive therapy Known symptomatic brain metastases requiring steroids History of or ongoing severe inflammatory skin conditions or severe eczema having required medical treatment Any prior or planned organ transplant Presence of any open, active wound requiring treatment