- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04725331
A Clinical Trial Assessing BT-001 Alone and in Combination With Pembrolizumab in Metastatic or Advanced Solid Tumors
February 23, 2024 updated by: Transgene
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.
Study Overview
Status
Recruiting
Conditions
Intervention / Treatment
Detailed Description
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.
Study Type
Interventional
Enrollment (Estimated)
48
Phase
- Phase 2
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Contact
- Name: Transgene EU, Clinical Operations Department
- Phone Number: + 33.3.88.27.91.00
- Email: clinicaltrials@transgene.fr
Study Locations
-
-
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Brussels, Belgium, 1200
- Recruiting
- Clinique Universitaire Saint-Luc
-
Principal Investigator:
- Pr Baurain
-
-
-
-
-
Bordeaux, France, 33000
- Recruiting
- Institut Bergonie
-
Principal Investigator:
- Pr Italiano
-
Lyon, France, 69008
- Recruiting
- Centre Leon Berard
-
Principal Investigator:
- Dr Cassier
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Paris, France, 75010
- Recruiting
- Hôpital Saint-Louis AP-HP
-
Principal Investigator:
- Pr Lebbé
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Villejuif, France, 94800
- Recruiting
- Institut Gustave Roussy
-
Principal Investigator:
- Dr Champiat
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
16 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Description
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
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Sequential Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Phase I, Part A - Dose escalation and safety of BT-001 alone
Dose escalation with repeated administrations of BT-001 directly into tumor as a single agent, in patients with metastatic or advanced solid tumors.
|
Oncolytic Vaccinia virus containing genes encoding the 4-E03 human recombinant anti-hCTLA4 antibody and human GM-CSF administered at different dose [Phase I, Part A]; one dose lower and at Recommended Dose for Part B [Phase I, Part B] by intra-tumoral (IT) route.
|
Experimental: Phase IIa - Expansion cohorts of BT-001 in combination with pembrolizumab
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.
|
Oncolytic Vaccinia virus containing genes encoding the 4-E03 human recombinant anti-hCTLA4 antibody and human GM-CSF administered at different dose [Phase I, Part A]; one dose lower and at Recommended Dose for Part B [Phase I, Part B] by intra-tumoral (IT) route.
Programmed death receptor (PD-1) blocking antibody administered at 200mg by intravenous (IV) infusions every 3 weeks.
Other Names:
|
Experimental: Phase I, Part B - Safety of BT-001 in combination with pembrolizumab
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)..
|
Oncolytic Vaccinia virus containing genes encoding the 4-E03 human recombinant anti-hCTLA4 antibody and human GM-CSF administered at different dose [Phase I, Part A]; one dose lower and at Recommended Dose for Part B [Phase I, Part B] by intra-tumoral (IT) route.
Programmed death receptor (PD-1) blocking antibody administered at 200mg by intravenous (IV) infusions every 3 weeks.
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Phase I: Safety and tolerability (Adverse Event reported per NCI-CTCAE v5.0)
Time Frame: Up to 5 years
|
Incidence of Adverse Event reported per NCI-CTCAE v5.0, Dose limiting toxicity and Serious Adverse Events.
|
Up to 5 years
|
Phase I, Part A: Recommended dose for Part B (RDPB) definition
Time Frame: Week 10-12
|
RDPB based on the safety data collected during the dose escalation phase (Phase I, Part A).
|
Week 10-12
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Phase IIa (except Soft Tissue Sarcoma cohort): Immune Overall Response Rate (iORR) by iRECIST
Time Frame: Up to 2 years
|
Percentage of patients whose best overall response is either a Complete Response or a Partial Response according to immune Response Evaluation Criteria In Solid Tumors (iRECIST) criteria over the the total number of evaluable patients.
for injected and non-injected lesion(s)
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Up to 2 years
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Phase IIa (Soft Tissue Sarcoma cohort): Immune Disease Control Rate (iDCR) at 6 months by iRECIST
Time Frame: Up to 6 months
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Percentage of patients whose best overall response is either a Complete Response, a Partial Response or Stable Disease according to immune Response Evaluation Criteria In Solid Tumors (iRECIST) criteria over the the total number of evaluable patients.
|
Up to 6 months
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Phase IIa: Safety and tolerability (Adverse Event reported per NCI-CTCAE v5.0)
Time Frame: Up to 5 years
|
Incidence of Adverse Event reported per NCI-CTCAE v5.0, Dose limiting toxicity and Serious Adverse Events.
|
Up to 5 years
|
Disease Control Rate (DCR) and immune DCR by RECIST version 1.1 and iRECIST
Time Frame: 4 months or 6 months
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Percentage of patients whose best overall response is either a Complete Response, a Partial Response or Stable Disease according to Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST 1.1) criteria or immune RECIST over the total number of evaluable patients.
|
4 months or 6 months
|
Progression Free Survival (PFS) and immune PFS duration by RECIST version 1.1 and iRECIST
Time Frame: Up to 2 years
|
Time from the first BT-001 administration to the date of first documented tumor progression according to Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST 1.1) criteria or immune RECIST or death due to any cause, whichever occurs first over evaluable patients
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Up to 2 years
|
Duration of overall Response (DoR) and immune DOR by RECIST version 1.1 and iRECIST
Time Frame: Up to 2 years
|
Time from the date of first documented response (CR or PR) to the date of first documented disease progression according to Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST 1.1) criteria or immune RECIST or the date of death due to underlying cancer over the number of patients whose Best Overall Response is Complete Response or Partial Response.
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Up to 2 years
|
Overall Survival (OS) duration
Time Frame: Up to 2 years
|
Time from first BT-001 administration to the date of death due to any cause over evalauable patients.
|
Up to 2 years
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
February 25, 2021
Primary Completion (Estimated)
April 30, 2025
Study Completion (Estimated)
April 30, 2025
Study Registration Dates
First Submitted
January 25, 2021
First Submitted That Met QC Criteria
January 25, 2021
First Posted (Actual)
January 26, 2021
Study Record Updates
Last Update Posted (Estimated)
February 26, 2024
Last Update Submitted That Met QC Criteria
February 23, 2024
Last Verified
February 1, 2024
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Pathologic Processes
- Skin Diseases
- Virus Diseases
- Infections
- Neoplasms, Connective and Soft Tissue
- Neoplasms by Histologic Type
- Neoplasms
- Neoplasms by Site
- Adenocarcinoma
- Carcinoma
- Neoplasms, Glandular and Epithelial
- Breast Diseases
- Neuroectodermal Tumors
- Neoplasms, Germ Cell and Embryonal
- Neoplasms, Nerve Tissue
- DNA Virus Infections
- Neoplastic Processes
- Tumor Virus Infections
- Neuroendocrine Tumors
- Nevi and Melanomas
- Polyomavirus Infections
- Carcinoma, Neuroendocrine
- Breast Neoplasms
- Sarcoma
- Neoplasm Metastasis
- Melanoma
- Triple Negative Breast Neoplasms
- Carcinoma, Merkel Cell
- Molecular Mechanisms of Pharmacological Action
- Antineoplastic Agents
- Antineoplastic Agents, Immunological
- Immune Checkpoint Inhibitors
- Pembrolizumab
Other Study ID Numbers
- BT-001.01
- 2020-000505-80 (EudraCT Number)
- MK3475-E37 (Other Identifier: Merck Sharp & Dohme LLC)
- KEYNOTE-E37 (Other Identifier: Merck Sharp & Dohme LLC)
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
No
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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