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

A Phase I/IIa Study of Intra-tumoral BT-001 (TG6030) Administered Alone and in Combination With Pembrolizumab in Patients With Cutaneous or, Subcutaneous Lesions or Easily Injectable Lymph Nodes of Metastatic/Advanced Solid Tumors.

This is a Phase I/IIa, multicenter, open-label, consecutive cohorts, dose-escalation study of BT-001 with repeated IT administrations alone and in combination with IV infusions of pembrolizumab.

This study will include 3 parts:

• Phase I, Part A: Repeated intra-tumoral (IT) administrations of BT-001 as a single agent, in patients with metastatic/advanced solid tumors; dose-escalation will be employed.
• Phase I, Part B: Repeated IT administrations of BT-001 in combination with intravenous (IV) infusions of pembrolizumab in patients with metastatic/advanced soft tissue sarcoma (STS), Merkel cell carcinoma (MCC), melanoma, triple negative breast cancer (TNBC) or non-small cell lung cancer (NSCLC)..
• Phase IIa: Repeated IT administrations of BT-001 in combination with IV infusions of pembrolizumab in several cohorts of patients with defined metastatic or advanced solid tumor conditions.

Inclusion Criteria:

• Have at least 1 injectable measurable cutaneous, subcutaneous or nodal lesion (direct injection or through the use of ultrasound guidance) not exceeding 50mm in longest diameter 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 and be 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 lung cancer, with cutaneous or, palpable subcutaneous lesions or easily injectable lymph nodes.
• 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 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
• 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 of immunosuppressive therapy within 28 days prior the first dose of study drugs
• Have a known additional malignancy that is progressing or has required active treatment 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 immunosuppressive drugs).
• Have a history of (non-infectious) pneumonitis / interstitial lung disease that required 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 IT injections
• Have had an allogenic tissue/solid organ transplant or allogenic stem cell or bone marrow 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-001 initiation.
• 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 known active CNS metastases and/or carcinomatous meningitis.
• Have a known history of Hepatitis B (defined as HBsAg reactive) or known active Hepatitis C virus (defined as HCV RNA [qualitative] is detected) infection.n.
• Woman of childbearing potential who has a positive serum pregnancy test (within 72 hours) prior to the start of treatment.
• Have received or receiving any live or live-attenuated vaccine within 30 days prior to the first dose of study intervention..
• History of myocarditis or congestive heart failure, unstable angina, uncontrolled infection, or myocardial infarction 6 months prior to clinical trial entry.
• Interstitial lung disease that is symptomatic and may interfere with the detection or management of suspected drug-related pulmonary toxicity
• 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
• Have severe hypersensitivity to the active substance or, to any of the excipients of (≥Grade 3) to pembrolizumab. and/or any of its excipients