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

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

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

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.

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