A Clinical Trial Assessing BT-001 Alone and in Combination With Pembrolizumab in Metastatic or Advanced Solid Tumors

Inclusion Criteria:

• Have at least 1 injectable measurable cutaneous, subcutaneous or nodal lesion (directinjection or through the use of ultrasound guidance) not exceeding 50mm in longestdiameter and whenever possible 1 distant non-injected measurable lesion.
• Provision of a fresh tumor sample of the lesion that will be injected first and,whenever possible, from another lesion that is planned to be injected, at baseline andbe willing to supply new tumor samples from a biopsy during treatment.
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1.
• Have adequate hematological, hepatic and renal functions.
• Have histologically confirmed, advanced/metastatic sarcoma (soft tissue and bone),Merkel cell carcinoma, melanoma, triple negative breast cancer or non-small cell lungcancer, with cutaneous or, palpable subcutaneous lesions or easily injectable lymphnodes.
• Have failed and/or are intolerant to standard therapeutic options.

Exclusion Criteria:

• Have had major surgery within 4 weeks of first study drug administration.
• Have received prior treatment with a vaccinia oncolytic virus.
• Have received prior systemic anti-cancer therapy including investigational agentswithin 4 weeks prior to the start of treatment.
• Have received prior radiotherapy within 2 weeks of start of study treatment or havehad a history of radiation pneumonitis
• Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form ofimmunosuppressive therapy within 28 days prior the first dose of study drugs
• Have a known additional malignancy that is progressing or has required activetreatment within the past 3 years.
• Have an active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressivedrugs).
• Have a history of (non-infectious) pneumonitis / interstitial lung disease thatrequired steroids or has current pneumonitis / interstitial lung disease
• Have an active infection requiring systemic therapy
• Have a known history of HIV infection
• Is taking an anticoagulant medication that cannot be interrupted prior to ITinjections
• Have had an allogenic tissue/solid organ transplant or allogenic stem cell or bonemarrow transplantation
• History of severe exfoliative skin conditions (e.g., eczema or atopic dermatitis)requiring systemic therapy for more than 4 weeks within 2 years prior to BT-001initiation.
• Have received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD L2 agent or withan agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g.,CTLA-4, OX 40, CD137), and was discontinued from that treatment due to a Grade 3 orhigher immune-related Adverse Event (irAE).
• Have known active CNS metastases and/or carcinomatous meningitis.
• Have a known history of Hepatitis B (defined as HBsAg reactive) or known activeHepatitis C virus (defined as HCV RNA [qualitative] is detected) infection.n.
• Woman of childbearing potential who has a positive serum pregnancy test (within 72hours) prior to the start of treatment.
• Have received or receiving any live or live-attenuated vaccine within 30 days prior tothe first dose of study intervention..
• History of myocarditis or congestive heart failure, unstable angina, uncontrolledinfection, or myocardial infarction 6 months prior to clinical trial entry.
• Interstitial lung disease that is symptomatic and may interfere with the detection ormanagement of suspected drug-related pulmonary toxicity
• Is currently participating in or has participated in a study of an investigationalagent or has used an investigational device within 4 weeks prior to the first dose ofstudy treatment
• Have severe hypersensitivity to the active substance or, to any of the excipients of (≥Grade 3) to pembrolizumab. and/or any of its excipients