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

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:
• 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)
• 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
• Locally advanced or metastatic cSCC (Cohort 3) that has not received systemic therapy (e.g., local resection or local topical therapy is permitted).
• 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