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

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ClinicalTrials.gov Identifier: NCT04725331
Recruitment Status : Recruiting
First Posted : January 26, 2021
Last Update Posted : March 15, 2021
Sponsor:
Collaborator:
BioInvent International AB
Information provided by (Responsible Party):
Transgene

Tracking Information
First Submitted Date  ICMJE January 25, 2021
First Posted Date  ICMJE January 26, 2021
Last Update Posted Date March 15, 2021
Actual Study Start Date  ICMJE February 25, 2021
Estimated Primary Completion Date November 30, 2024   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 25, 2021)
  • 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.
  • 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).
  • 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)
  • Phase IIa (Soft Tissue Sarcoma cohort): Immune Disease Control Rate (iDCR) at 6 months by iRECIST [ Time Frame: Up to 6 months ]
    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.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 25, 2021)
  • 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.
  • Disease Control Rate (DCR) and immune DCR by RECIST version 1.1 and iRECIST [ Time Frame: 4 months or 6 months ]
    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.
  • 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
  • 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.
  • 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.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Clinical Trial Assessing BT-001 Alone and in Combination With Pembrolizumab in Metastatic or Advanced Solid Tumors
Official Title  ICMJE 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.
Brief Summary 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.
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 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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Solid Tumor, Adult
  • Metastatic Cancer
  • Soft Tissue Sarcoma
  • Merkel Cell Carcinoma
  • Melanoma
  • Triple Negative Breast Cancer
  • Non Small Cell Lung Cancer
Intervention  ICMJE
  • 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.
Study Arms  ICMJE
  • 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.
    Intervention: Biological: BT-001
  • 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.
    Interventions:
    • Biological: BT-001
    • Biological: Pembrolizumab [Keytruda]
  • 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
    • Biological: Pembrolizumab [Keytruda]
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: January 25, 2021)
48
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE November 30, 2024
Estimated Primary Completion Date November 30, 2024   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Have at least 1 injectable measurable cutaneous, subcutaneous or nodal lesion (direct injection or through the use of ultrasound guidance) 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.
  • Provision of a fresh tumor sample of the largest lesion that is planned to be injected and, whenever possible, the largest lesion that is planned not 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. Adequate hematological, hepatic and renal functions.

For Phase I patients:

  • Have histologically confirmed, advanced/metastatic solid tumors including non-Hodgkin lymphoma (NHL) and preferably 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.

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.
  • Interstitial lung disease that is symptomatic and may interfere with the detection or management of suspected drug-related pulmonary toxicity
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Transgene EU, Clinical Operations Department + 33.3.88.27.91.00 clinicaltrials@transgene.fr
Listed Location Countries  ICMJE Belgium,   France
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04725331
Other Study ID Numbers  ICMJE BT-001.01
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Transgene
Study Sponsor  ICMJE Transgene
Collaborators  ICMJE BioInvent International AB
Investigators  ICMJE Not Provided
PRS Account Transgene
Verification Date March 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP