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

Study Purpose

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.

Recruitment Criteria

Accepts Healthy Volunteers

Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms

No
Study Type

An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.


An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.


Searching Both is inclusive of interventional and observational studies.

Interventional
Eligible Ages 18 Years and Over
Gender All
More Inclusion & Exclusion Criteria

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.
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  • - 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.
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  • - 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

Trial Details

Trial ID:

This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.

NCT04725331
Phase

Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.

Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.

Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.

Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.

Phase 1/Phase 2
Lead Sponsor

The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.

Transgene
Principal Investigator

The person who is responsible for the scientific and technical direction of the entire clinical study.

N/A
Principal Investigator Affiliation N/A
Agency Class

Category of organization(s) involved as sponsor (and collaborator) supporting the trial.

Industry
Overall Status Recruiting
Countries Belgium, France
Conditions

The disease, disorder, syndrome, illness, or injury that is being studied.

Metastatic Cancer, Soft Tissue Sarcoma, Merkel Cell Carcinoma, Melanoma, Triple Negative Breast Cancer, Non Small Cell Lung Cancer
Additional Details

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).
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  • - 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.

Arms & Interventions

Arms

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.

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)..

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.

Interventions

Biological: - BT-001

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.

Drug: - Pembrolizumab [KEYTRUDA®]

Programmed death receptor (PD-1) blocking antibody administered at 200mg by intravenous (IV) infusions every 3 weeks.

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

International Sites

Clinique Universitaire Saint-Luc, Brussels, Belgium

Status

Recruiting

Address

Clinique Universitaire Saint-Luc

Brussels, , 1200

Institut Bergonié, Bordeaux, France

Status

Recruiting

Address

Institut Bergonié

Bordeaux, , 33000

Centre Léon Bérard, Lyon, France

Status

Recruiting

Address

Centre Léon Bérard

Lyon, , 69008

Hôpital Saint-Louis AP-HP, Paris, France

Status

Recruiting

Address

Hôpital Saint-Louis AP-HP

Paris, , 75010

Institut Gustave Roussy, Villejuif, France

Status

Recruiting

Address

Institut Gustave Roussy

Villejuif, , 94800

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