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

• ClinicalTrials.gov Identifier: NCT04725331
• Recruitment Status: Recruiting
• First Posted: January 26, 2021
• Last Update Posted: July 15, 2022
• Sponsor: Transgene
• Collaborators: BioInvent International AB; Merck Sharp & Dohme LLC
• Information provided by (Responsible Party): Transgene

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Solid Tumor, Adult; Metastatic Cancer; Soft Tissue Sarcoma; Merkel Cell Carcinoma; Melanoma; Triple Negative Breast Cancer; Non Small Cell Lung Cancer	Biological: BT-001; Biological: Pembrolizumab [Keytruda]	Phase 1; Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 48 participants
• Allocation: Non-Randomized
• Intervention Model: Sequential Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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.
• Actual Study Start Date: February 25, 2021
• Estimated Primary Completion Date: April 30, 2025
• Estimated Study Completion Date: April 30, 2025

Arms and Interventions

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.	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.
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.	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.
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.	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.

Outcome Measures

Primary Outcome Measures :

1. 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.
2. 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).
3. 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)
4. 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.

Secondary Outcome Measures :

1. 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.
2. 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.
3. 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
4. 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.
5. 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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Contacts

Contact: Transgene EU, Clinical Operations Department; + 33.3.88.27.91.00; clinicaltrials@transgene.fr

Locations

Belgium

Clinique Universitaire Saint-Luc; Recruiting

Brussels, Belgium, 1200

Principal Investigator: Pr Baurain

France

Institut Bergonié; Recruiting

Bordeaux, France, 33000

Principal Investigator: Pr Italiano

Centre Léon Bérard; Recruiting

Lyon, France, 69008

Principal Investigator: Dr Cassier

Hôpital Saint-Louis AP-HP; Recruiting

Paris, France, 75010

Principal Investigator: Pr Lebbé

Institut Gustave Roussy; Recruiting

Villejuif, France, 94800

Principal Investigator: Dr Champiat

Sponsors and Collaborators

Transgene

BioInvent International AB

Merck Sharp & Dohme LLC

More Information

• Responsible Party: Transgene
• ClinicalTrials.gov Identifier: NCT04725331
• Other Study ID Numbers: BT-001.01; 2020-000505-80 ( EudraCT Number ); MK3475-E37 ( Other Identifier: Merck Sharp & Dohme LLC )
• First Posted: January 26, 2021
• Last Update Posted: July 15, 2022
• Last Verified: July 2022

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Transgene:

BT-001; Superficial tumors; Metastatic cancer; Intratumoral; Safety; Oncolytic virus; Vaccinia virus; Solid tumors; Melanoma; Merkel; Sarcoma; TNBC; NSCLC; Pembrolizumab; TG6030; Phase 1

Additional relevant MeSH terms:

Carcinoma, Merkel Cell; Melanoma; Sarcoma; Triple Negative Breast Neoplasms; Neoplasm Metastasis; Neoplasms; Neoplasms by Site; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Nerve Tissue; Nevi and Melanomas; Neoplasms, Connective and Soft Tissue; Breast Neoplasms; Breast Diseases; Skin Diseases; Neoplastic Processes; Pathologic Processes; Polyomavirus Infections; DNA Virus Infections; Virus Diseases; Infections; Tumor Virus Infections; Carcinoma, Neuroendocrine; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Pembrolizumab; Antineoplastic Agents, Immunological