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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Transgene

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

26 Feb 2021 → 22 Oct 2025

Decision date (initial)

2024-12-06

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

TRANSGENE

External identifiers

EU CT number

2024-518529-14-00

EudraCT number

2020-000505-80

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Dose response, Safety, Efficacy

Phase I Part A: ­Assess the local and systemic safety and tolerability of BT-001 as a single agent in repeated IT administrations at 10E6 to 10E8 PFU/mL; determine the Maximum Tolerated Dose (MTD).
Phase I, Part B: ­Assess the local and systemic safety and tolerability of BT-001 in repeated IT administrations, at the RDPB, in combination with IV infusions of pembrolizumab
Phase II: ­ Evaluate the antitumor activity of BT-001 in repeated IT administrations in combination with IV infusions of pembrolizumab.

Secondary objectives 9

1. Phase I-Part A and Phase I-Part B: Evaluate tumor response of injected and non-injected lesions using the Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1 and “Immune” RECIST (iRECIST),
2. Phase I-Part A, Phase I-Part B and Phase IIa: Assess BT-001 blood pharmacokinetics
3. Phase I-Part A, Phase I-Part B and Phase IIa:: Monitor GM-CSF and anti-CTLA-4 monoclonal antibody (mAb) (4-E03 mAb) concentrations in the blood and injected lesions.
4. Phase I-Part A, Phase I-Part B and Phase IIa::Assess immunogenicity by detecting anti-vaccinia Neutralizing Antibodies (NAbs), and antibodies against anti-CTLA-4 mAb (anti-4-E03 mAb) in the blood.
5. Phase I-Part A, Phase I-Part B and Phase IIa:: Assess immune changes in the tumor microenvironment for injected, and whenever possible, non-injected lesions.
6. Phase I-Part A, Phase I-Part B and Phase IIa: Perform BT-001 viral shedding analyses over time in urine, saliva, skin swabs and feces.
7. Phase I-Part A, Phase I-Part B and Phase IIa: Perform detection of viral DNA concentration in injected lesions, and whenever possible, in a non-injected lesion with response, skin swabs, saliva, urine, and feces.
8. Phase IIa: To evaluate the antitumor activity of BT-001 in repeated IT administrations in combination with IV infusions of pembrolizumab in patients with metastatic/advanced STS, MCC, melanoma, TNBC or NSCLC using RECIST 1.1.
9. Phase IIa: Assess the local and systemic safety and tolerability of BT-001 in repeated IT administrations in combination with IV infusions of pembrolizumab in patients with metastatic/advanced STS, MCC, melanoma, TNBC or NSCLC

Conditions and MedDRA coding

Metastatic/advanced soft tissue sarcoma (STS), Merkel cell carcinoma (MCC), melanoma, triple negative breast cancer (TNBC) or non-small cell lung cancer (NSCLC).

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 13

1. Provide signed written informed consent
2. Be male or female patient aged ≥ 18 years.
3. Have histologically confirmed, advanced/metastatic sarcoma (soft tissue and bone), MCC, melanoma, TNBC, or NSCLC, with cutaneous or, palpable subcutaneous lesions or, easily injectable lymph nodes
4. Have failed and/or are intolerant to standard therapeutic options
5. Have at least 1 injectable cutaneous, subcutaneous or nodal lesion
6. Have an expected survival of at least 3 months
7. Have knowledge of his/her anti-variola vaccine status.
8. Agree to provide a fresh tumor sample of the lesion that will be injected first
9. Have an Eastern Cooperative Oncology Group performance status of 0 or 1
10. Use a highly effective contraception method combined with a barrier method during and after study treatment
11. Have received complete COVID-19 primary-vaccination at least 30 days before first IMP(s) administration.
12. Have an interval of at least 3 weeks between first IMP(s) administration and exposure to prior chemotherapy
13. Have adequate hematological, hepatic, and renal functions.

Exclusion criteria 29

1. Have a tumor adjacent to the trachea or a major blood vessel for planned injection.
2. Have had major surgery within 4 weeks of first IMP(s) administration
3. Have received prior treatment with a vaccinia oncolytic virus
4. Have received antiviral therapy active on vaccinia virus (VV), e.g., ribavirin, interferon/pegylated interferon
5. 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)
6. Have received prior systemic anti-cancer therapy including investigational agents within 4 weeks prior to the start of treatment
7. Have received prior radiotherapy within 2 weeks of start of study treatment or have had a history of radiation pneumonitis
8. Have received a live or live-attenuated vaccine within 30 days prior to the first dose of study intervention
9. A Women Of ChildBearing Potential who has a positive serum pregnancy test (within 72 hours) prior to the start of treatment
10. 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
11. Is taking an anticoagulant medication that cannot be interrupted prior to IT injections
12. Have had an allogeneic tissue/solid organ transplant or allogeneic stem cell or bone marrow transplantation
13. 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
14. Has a known additional malignancy that is progressing or has required active treatment within the past 3 years.
15. Has known active CNS metastases and/or carcinomatous meningitis.
16. Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients
17. Has 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).
18. Has a history of (non-infectious) pneumonitis / interstitial lung disease that required steroids or has current pneumonitis / interstitial lung disease
19. Has an active infection requiring systemic therapy
20. Has a known history of HIV infection. No HIV testing is required unless mandated by local health authority
21. Has a known history of Hepatitis B (defined as HBsAg reactive) or known active Hepatitis C virus (defined as HCV RNA [qualitative] is detected) infection
22. 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, such that it is not in the best interest of the participant to participate, in the opinion of the treating investigator
23. Has a known psychiatric or substance abuse disorder that would interfere with the participant’s ability to cooperate with the requirements of the study
24. Has received radiation therapy to the lung that is >30Gy within 6 months of the first dose of trial treatment for patients having NSCLC
25. 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
26. Have known hypersensitivity to egg or to any excipients of BT-001
27. Have a history of myocarditis or congestive heart failure (as defined by New York Heart Association Functional Classification III or IV), unstable angina pectoris, uncontrolled infection, or myocardial infarction 6 months prior to clinical trial entry.
28. COVID-19 vaccination or infection within 2 weeks prior to start of treatment
29. History of monkeypox infection or anti-monkeypox vaccination within 30 days prior to the first dose of study intervention

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 3

1. Phase I part: Overall incidence of AEs and DLTs, SAEs
2. Phase IIa part - Soft Tissue Sarcoma cohort: Progression Free Rate at 6-months according to iRECIST
3. Phase IIa part - All cohorts except Soft Tissue Sarcoma : Immune Overall Response Rate according to iRECIST.

Secondary endpoints 4

1. Overall incidence of AEs and DLTs, SAEs (Phase IIa part)
2. Disease Control rate overall and at 4-month using RECIST 1.1 and iRECIST
3. Progression Free Survival using RECIST 1.1 and iRECIST
4. Overall Survival

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Auxiliary 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Transgene

Sponsor organisation

Transgene

Address

Parc D Innovation, 400 Boulevard Gonthier D Andernach, Cs 80166 Illkirch Graffenstaden, Illkirch Graffenstaden 400 Boulevard Gonthier D Andernach Cs 80166 Illkirch Graffenstaden

City

Illkirch Cedex

Postcode

67405

Country

France

Scientific contact point

Organisation

Transgene

Contact name

Julien Romanetto

Public contact point

Organisation

Transgene

Contact name

Julien Romanetto

Locations

2 EU/EEA countries · 5 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 29 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

7 submissions — initial application plus substantial / non-substantial modifications