A phase I/IIa clinical study of BT-001 in the treatment of patients withmetastatic or advanced solid cancer.

Phase 1

Conditions: Phase I: Advanced or metastatic solid tumors including Non-Hodgkin Lymphoma (NHL) and preferably Soft Tissue Sarcoma, Merkel Cell Carcinoma, Melanoma, Triple Negative Breast Cancer, Non Smal Cell Lung Cancer Phase IIa: Soft Tissue Sarcoma, Merkel Cell Carcinoma, Melanoma, Triple Negative Breast Cancer, Non Smal Cell Lung Cancer
MedDRA version: 21.1Level: LLTClassification code 10065252Term: Solid tumorSystem Organ Class: 100000004864
Therapeutic area: Diseases [C] - Cancer [C04]

Registration Number: EUCTR2020-000505-80-FR

Lead Sponsor: TRANSGENE

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

Sex: All

Target Recruitment: 48

Inclusion Criteria

I1. Signed informed consent in accordance to ICH-GCP and national/local regulation before starting any protocol-related procedures
I2. Male or female patient aged = 18 years
I3. At least 1 injectable measurable cutaneous, subcutaneous or nodal lesion greater or equal to 2 cm in longest diameter; or multiple injectable lesions (maximum 5) that in aggregate have a longest diameter of at least 2 cm, and whenever possible 1 distant non-injected measurable lesion
I4. Expected survival of at least 3 months
I5. Knowledge of his/her anti-variola vaccine status
I6. Provide a fresh tumor sample at baseline and be willing to supply new tumor samples from a biopsy during treatment.
I7. ECOG performance status of 0 or 1
I8. Interval of at least 3 weeks between first study drug injection and exposure to prior chemotherapy; 4 weeks for immunotherapy and antibody-based therapy and 2 weeks for palliative radiotherapy
I9. Adequate hematological, hepatic and renal functions:
Haemoglobin = 9 g/dL
Neutrophils = 1 x10E+9/L
Lymphocytes = 0.750 x 10E+9/L
Platelets = 100 x10E+9/L
Alanine aminotransferase (ALT) and aspartate aminotransferase [AST]) = 3 x ULN (up to 5 x ULN if patients exhibits liver metastases); total bilirubin = 1.5 x ULN except for patients with Gilbert’s syndrome who may be included if total bilirubin = 2.5 x ULN
Serum creatinine = 1.5 x ULN or creatinine clearance = 60 mL/min according to Cockroft & Gault formula
International normalized ratio (INR) = 1.5
I10.Appropriate precaution against pregnancy whilst on study:
- Women of childbearing potential (WOCBP) potential must have a negative pregnancy test prior to study entry.
- Both men and WOCBP must be using a highly effective contraception method combined with a barrier method (e.g. condom) during BT-001 treatment period and for a minimum of 4 months following the last administration of BT-001

For patients included in Phase I (parts A and B):
IA-1Have histologically confirmed, advanced/metastatic solid tumors including non-Hodgkin lymphoma (NHL) and preferably sarcoma (soft tissue and bone), MCC, melanoma, TNBC or NSCLC, with cutaneous or, palpable subcutaneous lesions or easily injectable lymph nodes

For patients included in Phase I, Part A (single agent) only:
IB-1 Patients who have failed and/or are intolerant to standard therapeutic options.

For patient included in Phase IIa:
IC- Soft Tissue Sarcoma (STS) Cohort:
IC-1Have a histologically confirmed metastatic and/or locally advanced inoperable undifferentiated pleomorphic sarcoma/myxofibrosarcoma, cutaneous angiosarcoma, dedifferentiated liposarcoma or leiomyosarcoma.
IC-2Have at least 1 injectable cutaneous or, palpable subcutaneous soft tissue or nodal lesion = 20 mm in longest diameter.
IC-3Have at least one prior line of systemic therapy. A naive patient may be enrolled if they have refused standard systemic treatment. Prior adjuvant therapy will not count if it was completed more than 6 months previously.
ID- Merkel Cell Carcinoma (MCC):
ID-1Have histologically confirmed stage IV MCC.
ID-2Have received at least 1 line of treatment for metastatic MCC and have progressed after the most recent line of treatment.
IE- Melanoma:
IE-1.Have pathologically confirmed metastatic or unresectable stage IIIb/c of IV melanoma with at least one cutaneous or, subcutaneous tumor or palpable lymph node amenable to IT injection.
IE-2.Have had prior treatment with anti-PD-1 or anti-PD-L1 agents

Exclusion Criteria

E1 Have a tumor adjacent to the trachea or a major blood vessel.
E2 Have had major surgery within 4 weeks of first study drug administration.
E3 Have received prior treatment with a vaccinia oncolytic virus.
E4 Have known significant immunodeficiency due to underlying illness (e.g., HIV/AIDS) and/or immune-suppressive medication including systemic corticosteroids.
E5 Have received antiviral therapy active on vaccinia virus (VV), e.g., ribavirin, interferon/pegylated interferon.
E6 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.
E7 Have 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.
E8 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).
E9 Have received treatment with another investigational agent within 21 days before the inclusion.
E10 Taken an anticoagulant medication that cannot be interrupted prior to IT injections.
E11 Have active brain metastasis (stable and treated metastasis are accepted).
E12 Have had any organ transplantation, including allogenic stem cell or bone marrow transplantation.
E13 Have known hypersensitivity to egg.
E14 Have had any positive test for hepatitis C virus (HCV) or hepatitis B virus (HBV) indicating acute or chronic infection.
E15 Are pregnant or a breastfeeding woman, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test (> 10 mIU/mL).
E16Have any medical, familial, sociological or psychiatric condition that in the opinion of the investigator would prohibit inclusion in the trial.

For patients included in Phase I, Part B and IIa only:
EA-1. 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.
EA-2. Have interstitial lung disease that is symptomatic and may interfere with the detection or management of suspected drug-related pulmonary toxicity.
EA-3. Have known hypersensitivity to the active substance or to any of the excipients of pembrolizumab.

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method

Secondary Outcome Measures

Name	Time	Method

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