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 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: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2020-000505-80-BE
• Lead Sponsor: TRANSGENE

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2020-08-05
• Last Update Posted: 15 July 2024

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 258

Inclusion Criteria

Phase I part B and Phase IIa
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 Histologically confirmed, advanced/metastatic sarcoma (soft tissue and bone), MCC, melanoma, Triple TNBC, or NSCLC, with cutaneous or, palpable subcutaneous lesions or, easily injectable lymph nodes
I4 Failed and/or are intolerant to standard therapeutic options
I5 At least 1 injectable cutaneous, subcutaneous or nodal lesion measurable according to RECIST 1.1 and not exceeding 50mm in the longest diameter and whenever possible another non-injected measurable lesion
I6 Expected survival of at least 3 months.
I7 Knowledge of his/her anti-variola vaccine status
I8 Agree to provide a fresh tumor sample of the lesion
I9 ECOG status of 0 or 1
I10 Highly effective contraception method combined with a barrier method during and after study treatment
I11 Complete COVID-19 primary-vaccination
I12 Interval of at least 3 weeks between first IMP(s) administration and exposure to prior chemotherapy, 4 weeks for immunotherapy and antibody-based therapy, and 2 weeks for palliative radiotherapy
I13 Have adequate hematological, hepatic and renal functions:
Hemoglobin = 9 g/dL (without packed red blood cell transfusion
within the prior 2 weeks)
Neutrophils = 1.5 x10E9/L
Lymphocytes = 0.750 x 10E9/L
Platelets =100 x10E9/L
ALT and AST = 2.5 x ULN; total bilirubin is = 1.5 x ULN
Total bilirubin = 1.5 x ULN, except for patients with Gilbert syndrome who must have a total bilirubin level < 3.0 x ULN
Lactate dehydrogenase = 3 x ULN
Creatinine clearance = 60 mL/min according to the Cockroft & Gault formula
International normalized ratio (INR) = 1.5 x ULN

Additional criteria applicable according to patient's condition:
IC- Soft Tissue Sarcoma (STS) Cohort:
IC-1 Have a histologically confirmed metastatic and/or locally advanced inoperable undifferentiated pleomorphic sarcoma/myxofibrosarcoma, cutaneous angiosarcoma, dedifferentiated liposarcoma or leiomyosarcoma.
IC-2 Have at least 1 injectable cutaneous or, palpable subcutaneous soft tissue or nodal lesion.
IC-3 Have failed and/or are intolerant to standard therapeutic options.
ID- Merkel Cell Carcinoma (MCC):
ID-1 Have histologically confirmed unresectable stage III or metastatic MCC.
ID-2 Have failed and/or are intolerant to standard therapeutic options.
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 failed and/or are intolerant to prior treatment with anti-PD-1 or anti-PD-L1 agents alone or in combination with anti-CTLA-4.
IE-3 Have received therapy targeting BRAF or MEK when appropriate and have failed and/or are intolerant to it
IE-4 Do not have disease that is suitable for local therapy with curative intent
IE-5 Have not received previous treatment with Imlygic
IF- Triple Negative Breast Cancer (TNBC):
IF-1 Have metastatic or locally advanced, histologically confirmed TNBC characterized by absence of human epidermal growth factor 2, estrogen receptor, and progesterone receptor expression.
IF-2 Have failed and/or are intolerant to standard therapeutic options.
IF-3 Have documented disease progression on or after the most recent therapy.
IG- Non-Small Cell Lung Cancer (NSCLC):
IG-1. Have histologically confirmed NSCLC, stage IIIb-IV or delayed

Exclusion Criteria

Phase I Part B and Phase IIa:
E1 Have a tumor adjacent to the trachea or a major blood vessel for planned injection.
E2 Have had major surgery within 4 weeks of first IMP(s) Phase I Part B and Phase IIa:
E1 Have a tumor adjacent to the trachea or a major blood vessel for planned injection.
E2 Have had major surgery within 4 weeks of first IMP(s) administration.
E3 Have received prior treatment with a vaccinia oncolytic virus.
E4 Have received antiviral therapy active on vaccinia virus (VV), e.g., ribavirin, interferon/pegylated interferon..
E5 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 coinhibitory T-cell receptor (e.g., CTLA-4, OX 40, CD137), and was discontinued from that treatment due to a Grade 3 or higher immunerelated
Adverse Event (irAE).
E6 Have received prior systemic anti-cancer therapy including investigational agents within 4 weeks prior to the start of treatment.
E7 Have received prior radiotherapy within 2 weeks of start of study treatment or have had a history of radiation pneumonitis.
E8 Have received a live or live-attenuated vaccine within 30 days prior to the first dose of study intervention.
E9 A WOCBP who has a positive serum pregnancy test (within 72 hours) prior to the start of treatment.
E10 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.
E11 Is taking an anticoagulant medication that cannot be interrupted prior to IT injections.
E12 Have had an allogenic tissue/solid organ transplant or allogenic stem cell or bone marrow transplantation.
E13 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.
E14 Has a known additional malignancy that is progressing or has required active treatment within the past 3 years.
E15 Has known active CNS metastases and/or carcinomatous meningitis.
E16 Has severe hypersensitivity (=Grade 3) to pembrolizumab and/or any of its excipients.
E17 Has an active autoimmune disease that has required systemic treatment in past 2 years.
E18 Has a history of (non-infectious) pneumonitis / interstitial lung disease that required steroids or has current pneumonitis / interstitial lung disease.
E19 Has an active infection requiring systemic therapy.
E20 Has a known history of HIV infection.
E21 Has a known history of Hepatitis B or known active Hepatitis C virus infection.
E22 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
E23 Has a known psychiatric or substance abuse disorder that would interfere with the participant's ability to cooperate with the requirements of the study
E24 Has received radiation therapy to the lung that is >30Gy within 6 months of the first dose of trial treatment for patients having NSCLC
E25 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
E26 Have known hypersensitivity to egg or to any excipients of BT-001
E27 Have a history of myocarditis or congestive heart failure, unstable
angina pectoris, uncontroll

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified