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) 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.

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.

Solid Tumor, Adult, 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 or advanced solid tumors.
  • - 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 solid tumors.

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] and at Recommended Dose for Part B [Phase I, Part B and Phase IIa] by intra-tumoral (IT) route.

Biological: - 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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