Study of TBio-6517 Given Alone or in Combination With Pembrolizumab in Solid Tumors

Key Inclusion Criteria:

* Have a histologically or pathologically documented, locally-advanced or metastatic solid tumor for which standard curative measures do not exist or are no longer effective
* Measurable disease as per RECIST 1.1 criteria
* At least one tumor amenable to safe ITu injections and biopsies
* ECOG performance status 0 or 1
* Demonstrate adequate organ function
* Must be willing to comply with all protocol procedures and adhere to post-treatment care instructions
* Additional Inclusion criteria exist

For patients in phase 2 only: Have a histologically or cytologically confirmed advanced (metastatic and/or unresectable) solid tumor listed below, that is incurable and for which prior standard treatment has failed:

1. Advanced (unresectable) or metastatic, intra or extra hepatic adenocarcinoma originating from the bile duct, CCA (Cohort 1) having progressed on at least 1 line of systemic therapy (including targeted therapy if eligible)
2. Locally advanced or metastatic cutaneous melanoma (Cohort 2) that has failed anti-PD-1 or anti-PDL1 therapy (+/- anti-CTLA-4 therapy) and if BRAF+, having failed a BRAF/ +/-MEK inhibitor
3. Locally advanced or metastatic cSCC (Cohort 3) that has not received systemic therapy (e.g., local resection or local topical therapy is permitted).
4. Locally advanced or metastatic MSS-CRC (Cohort 4) patients that have progressed on at least 2 prior lines of systemic therapy which should include irinotecan and oxaliplatin +/- targeted therapy if warranted.

Key Exclusion Criteria:

* Prior systemic therapy, including experimental, surgery or radiation therapy within 4 weeks and must have recovered from acute toxicity.
* Prior treatment with any oncolytic virus.
* Requires use of anti-platelet or anti-coagulant therapy that cannot be safely suspended for per protocol biopsies or intra-tumoral injections.
* CNS metastases and/or carcinomatous meningitis that have not been completely resected or completely irradiated.
* Prior history of myocarditis
* Symptomatic or asymptomatic cardiovascular disease
* Known HIV/AIDS, active HBV or HCV infection.
* Received immunosuppressive medication within 4 weeks. (\>10mg/day prednisone)
* Known intolerance to anti-PD-1 or anti-PD-L1 antibody therapy
* Additional Exclusion criteria exist