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

Prior treatment

• Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study treatment
• Is taking an anticoagulant medication that cannot be interrupted prior to IT injections
• Have had an allogeneic tissue/solid organ transplant or allogeneic stem cell or bone marrow transplantation
• Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 28 days prior the first dose of study drugs
• Have had major surgery within 4 weeks of first IMP(s) administration
• Has received radiation therapy to the lung that is >30Gy within 6 months of the first dose of trial treatment for patients having NSCLC
• Have a 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-001 initiation
• Have a history of myocarditis or congestive heart failure (as defined by New York Heart Association Functional Classification III or IV), unstable angina pectoris, uncontrolled infection, or myocardial infarction 6 months prior to clinical trial entry.
• COVID-19 vaccination or infection within 2 weeks prior to start of treatment
• History of monkeypox infection or anti-monkeypox vaccination within 30 days prior to the first dose of study intervention
• Have received prior treatment with a vaccinia oncolytic virus
• Have received antiviral therapy active on vaccinia virus (VV), e.g., ribavirin, interferon/pegylated interferon
• Have received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD L2 agent or with an 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 or higher immune-related Adverse Event (irAE)
• Have received prior systemic anti-cancer therapy including investigational agents within 4 weeks prior to the start of treatment
• Have received prior radiotherapy within 2 weeks of start of study treatment or have had a history of radiation pneumonitis
• Have received a live or live-attenuated vaccine within 30 days prior to the first dose of study intervention

Other illness

• Has a known additional malignancy that is progressing or has required active treatment within the past 3 years.
• Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients
• Has an active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs).
• Has a history of (non-infectious) pneumonitis / interstitial lung disease that required steroids or has current pneumonitis / interstitial lung disease
• Has an active infection requiring systemic therapy
• Has a known history of HIV infection. No HIV testing is required unless mandated by local health authority
• Has a known history of Hepatitis B (defined as HBsAg reactive) or known active Hepatitis C virus (defined as HCV RNA [qualitative] is detected) infection
• Has a known psychiatric or substance abuse disorder that would interfere with the participant’s ability to cooperate with the requirements of the study
• Have known hypersensitivity to egg or to any excipients of BT-001

Lab values

• Has a history or current evidence of any condition, therapy, or laboratory abnormality, or other circumstance that might confound the results of the study or interfere with the participant's participation for the full duration of the study, such that it is not in the best interest of the participant to participate, in the opinion of the treating investigator
• A Women Of ChildBearing Potential who has a positive serum pregnancy test (within 72 hours) prior to the start of treatment

Other

• Have a tumor adjacent to the trachea or a major blood vessel for planned injection.
• Has known active CNS metastases and/or carcinomatous meningitis.

• Provide signed written informed consent
• Use a highly effective contraception method combined with a barrier method during and after study treatment
• Have received complete COVID-19 primary-vaccination at least 30 days before first IMP(s) administration.
• Have an interval of at least 3 weeks between first IMP(s) administration and exposure to prior chemotherapy
• Have adequate hematological, hepatic, and renal functions.
• Be male or female patient aged ≥ 18 years.
• Have histologically confirmed, advanced/metastatic sarcoma (soft tissue and bone), MCC, melanoma, TNBC, or NSCLC, with cutaneous or, palpable subcutaneous lesions or, easily injectable lymph nodes
• Have failed and/or are intolerant to standard therapeutic options
• Have at least 1 injectable cutaneous, subcutaneous or nodal lesion
• Have an expected survival of at least 3 months
• Have knowledge of his/her anti-variola vaccine status.
• Agree to provide a fresh tumor sample of the lesion that will be injected first
• Have an Eastern Cooperative Oncology Group performance status of 0 or 1