A Clinical Trial of TG6050 in Patients With Metastatic Non-Small Cell Lung Cancer (Delivir)

Non-small Cell Lung Cancer Clinical Trial

Official title:

A Phase I Dose-escalation Trial of TG6050 Administered by Intravenous Infusion in Patients With Advanced Non-small Cell Lung Cancer (NSCLC)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05788926
• Other study ID #: TG6050.01
• Status: Recruiting
• Phase: Phase 1
• Start date: April 5, 2023
• Est. completion date: March 31, 2025

Study information

• Verified date: October 2023
• Source: Transgene
• Contact: Transgene EU, Clinical Operations Department
• Phone: + 33.3.88.27.91.00
• Email: clinicaltrials[@]transgene.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a phase I, open-label, dose-escalation trial of TG6050 administered by single or repeated IV infusion(s).

Description:

This clinical trial aims at determining the dose and schedule of administration of TG6050 for further development, primarly based on the assessment of the safety and tolerability of single and repeated IV infusions at escalating doses in patients with advanced NSCLC.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 36
• Est. completion date: March 31, 2025
• Est. primary completion date: October 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

1. Signed written informed consent in accordance with International Conference on Harmonization-Good Clinical Practice and national/local regulations

2. Male or female patient aged 18 to 75 years

3. Histologically confirmed metastatic (stage IV) NSCLC

4. No known oncogenic driver alteration with available targeted therapy, including EGFR, HER2, KRASG12C, MET or BRAFV600E gene mutations and ALK, ROS1, or RET gene fusion/rearrangements. Patients with KRASG12C mutation having received a targeted therapy will be eligible

5. Have received all standard therapeutic options available, including at least 4 months of treatment with an anti-PD1 or PD-L1 monoclonal antibody and doublet platinum-containing chemotherapy

6. Have documented progression not earlier than 4 months after initiation of the anti-PD(L)1 therapy

7. Have at least one measurable lesion according to RECIST 1.1 and at least one lesion amenable to biopsy

8. Expected life expectancy of at least 3 months

9. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

10. Time from prior immunotherapy or antibody-based therapy to first TG6050 administration of at least 4 weeks, from prior chemotherapy of at least 3 weeks, and from palliative radiotherapy of at least 2 weeks

11. Adequate hematological, hepatic, and renal functions

12. Clearance for trial participation after cardiology consultation and cardiologic investigations

13. Negative pregnancy test in women of childbearing potential (WOCBP)

14. Commitment to use a highly effective contraception method (i.e., with a failure rate of =1 % per year) combined with a barrier method (e.g., condom) during TG6050 administration period and at least 3 months after TG6050 administration, in men and WOCBP

Exclusion Criteria:

1. Major surgery within 4 weeks of first TG6050 administration

2. Prior treatment with ipilimumab

3. Prior treatment with an oncolytic virus

4. Prior treatment with another investigational agent within 4 weeks of first TG6050 administration

5. Immunodeficiency due to underlying illness and/or immune-suppressive medication

6. Uncontrolled intercurrent illness

7. Active auto-immune disease except hypothyroidism or type I diabetes only requiring hormone replacement therapy

8. Brain metastases, unless treated and stable for at least 4 weeks after medical imaging assessment

9. Other malignancies than NSCLC except cutaneous basal cell carcinoma and in situ carcinoma of the uterine cervix, unless complete remission for at least 5 years prior to trial entry and no therapy required during the trial

10. Ongoing antiviral therapy active on vaccinia virus (VV), e.g., ribavirin, interferon/pegylated interferon

11. History of monkeypox infection or anti-monkeypox vaccination

12. History of severe exfoliative skin conditions

13. History of grade = 3 auto-immune manifestations related to ICI therapy

14. History of severe systemic reaction or side-effect after a smallpox vaccination

15. History of solid organ or allogeneic stem cell transplantation

16. Known hypersensitivity to eggs or any TG6050 excipients

17. Positive test for hepatitis C virus (HCV) or hepatitis B virus (HBV) indicating acute or chronic infection

18. Live virus vaccination within 28 days of TG6050 administration

19. COVID-19 vaccination or infection within 14 days of TG6050 administration

20. Breastfeeding woman

21. Any medical, familial, sociological, or psychiatric condition that in the opinion of the investigator would prohibit inclusion in the trial

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Non-small Cell Lung Cancer

Intervention

Drug:
• TG6050
Oncolytic Vaccinia virus containing genes encoding the human interleukin 12 (IL-12) and an anti-CTLA4 antibody administered at different dose.

Locations

Country	Name	City	State
France	Institut Bergonié	Bordeaux
France	Hôpital Timone	Marseille
France	Hôpital Européen Georges Pompidou	Paris
France	CHU Rennes - Hôpital Pontchaillou	Rennes
France	Institut de Cancérologie de l'Ouest	Saint-Herblain

Sponsors (1)

Lead Sponsor	Collaborator
Transgene

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety and tolerability (Adverse Event reported per NCI-CTCAE v5.0)	Incidence of Adverse Event reported per NCI-CTCAE v5.0, Dose limiting toxicity, Maximal tolerated dose, Maximum feasible dose and Serious Adverse Events.	Up to 5 years
Secondary	Overall response rate (ORR)	Proportion of patients whose best response during their participation in the trial is either complete response (CR) or partial response (PR)	Up to 1 year
Secondary	4-month disease control rate	Proportion of patients whose tumor assessment at 4 months is either complete response (CR), partial response (PR), or stable disease (SD)	Up to 4 months
Secondary	Overall disease control rate (DCR)	Proportion of patients whose tumor assessment is either complete response (CR), partial response (PR), or stable disease (SD) during their trial participation	Up to 1 year
Secondary	Progression-free survival (PFS)	Time from the first TG6050 infusion to documented tumor progression or death due to any cause.	Up to 1 year
Secondary	Overall survival (OS)	Time from the first TG6050 infusion to death due to any cause.	Up to 1 year
Secondary	Duration of overall response (DoR)	Time from the first documented response (complete response (CR) or partial response (PR)) to documented tumor progression or death due to underlying cancer.	Up to 1 year
Secondary	Molecular responses (MR)	Circulating tumor DNA (ctDNA) levels and changes over time	Up to 1 year