A Clinical Trial Assessing BT-001 Alone and in Combination With Pembrolizumab in Metastatic or Advanced Solid Tumors
Metastatic Cancer, Soft Tissue Sarcoma, Merkel Cell Carcinoma
About this trial
This is an interventional treatment trial for Metastatic Cancer focused on measuring Superficial tumors, Metastatic cancer, Intratumoral, Safety, Oncolytic virus, Vaccinia virus, Solid tumors, Melanoma, Merkel, Sarcoma, TNBC, NSCLC, Pembrolizumab, BT-001, TG6030, Phase 1
Eligibility Criteria
Inclusion Criteria:
- Have at least 1 injectable measurable cutaneous, subcutaneous or nodal lesion (direct injection or through the use of ultrasound guidance) measuring between 25 and 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.
For Phase I patients:
- 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.
- Known significant immunodeficiency due to underlying illness (e.g., HIV/AIDS) and/or immune-suppressive medication including systemic corticosteroids.
- 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.
- Uncontrolled intercurrent illness including but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia or psychiatric illness/social circumstances that could limit compliance with study requirements.
- Have had a Grade ≥ 3 auto-immune manifestations of previous ICIs (e.g., anti-PD-1, anti-PDL1, anti-CTLA-4, or another immune checkpoint targeting agent under investigation).
- Active brain metastasis (stable and treated metastasis are accepted). E8. Known hypersensitivity to egg or to any excipients of BT-001.
- Have had any positive test for hepatitis C virus (HCV) or hepatitis B virus (HBV) indicating acute or chronic infection.
- Pregnant or a breastfeeding woman.
- Have received or receiving any live vaccine during the period of 28 days before IMP(s) administration, during IMP's administrations and 28 days after the last IMP's administration.
- History of myocarditis or congestive heart failure, 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
For patients included in Phase I, Part B and IIa only:
• Patient with an active known or suspected auto-immune disease. Patient with type I diabetes or hypothyroidism only requiring hormone replacement are permitted to enroll.
Sites / Locations
- Clinique Universitaire Saint-LucRecruiting
- Institut BergoniéRecruiting
- Centre Léon BérardRecruiting
- Hôpital Saint-Louis AP-HPRecruiting
- Institut Gustave RoussyRecruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Experimental
Experimental
Experimental
Phase I, Part A - Dose escalation and safety of BT-001 alone
Phase I, Part B - Safety of BT-001 in combination with pembrolizumab
Phase IIa - Expansion cohorts of BT-001 in combination with pembrolizumab
Dose escalation with repeated administrations of BT-001 directly into tumor as a single agent, in patients with metastatic or advanced solid tumors.
Repeated administrations of BT-001 directly into tumor in combination with infusions of pembrolizumab in patients with metastatic or advanced soft tissue sarcoma (STS), Merkel cell carcinoma (MCC), melanoma, triple negative breast cancer (TNBC) or non-small cell lung cancer (NSCLC)..
Repeated administrations of BT-001 directly into tumor in combination with infusions of pembrolizumab in several cohorts of patients with defined metastatic or advanced solid tumor conditions: soft tissue sarcoma, Merkel cell carcinoma, melanoma, triple negative breast cancer, non-small cell lung cancer.