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

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

Detailed 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.

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

Conditions
-----------------
Non-small Cell Lung Cancer

Intervention / Treatment
-----------------
* Drug: TG6050


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Signed written informed consent in accordance with International Conference on Harmonization-Good Clinical Practice and national/local regulations Male or female patient aged 18 to 75 years Histologically confirmed metastatic (stage IV) NSCLC 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 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 Have documented progression not earlier than 4 months after initiation of the anti-PD(L)1 therapy Have at least one measurable lesion according to RECIST 1.1 and at least one lesion amenable to biopsy Expected life expectancy of at least 3 months Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 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 Adequate hematological, hepatic, and renal functions Clearance for trial participation after cardiology consultation and cardiologic investigations Negative pregnancy test in women of childbearing potential (WOCBP) 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: Major surgery within 4 weeks of first TG6050 administration Prior treatment with ipilimumab Prior treatment with an oncolytic virus Prior treatment with another investigational agent within 4 weeks of first TG6050 administration Immunodeficiency due to underlying illness and/or immune-suppressive medication Uncontrolled intercurrent illness Active auto-immune disease except hypothyroidism or type I diabetes only requiring hormone replacement therapy Brain metastases, unless treated and stable for at least 4 weeks after medical imaging assessment 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 Ongoing antiviral therapy active on vaccinia virus (VV), e.g., ribavirin, interferon/pegylated interferon History of monkeypox infection or anti-monkeypox vaccination History of severe exfoliative skin conditions History of grade ≥ 3 auto-immune manifestations related to ICI therapy History of severe systemic reaction or side-effect after a smallpox vaccination History of solid organ or allogeneic stem cell transplantation Known hypersensitivity to eggs or any TG6050 excipients Positive test for hepatitis C virus (HCV) or hepatitis B virus (HBV) indicating acute or chronic infection Live virus vaccination within 28 days of TG6050 administration COVID-19 vaccination or infection within 14 days of TG6050 administration Breastfeeding woman Any medical, familial, sociological, or psychiatric condition that in the opinion of the investigator would prohibit inclusion in the trial

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dose escalation of TG6050<br>Dose escalation with single or repeated administrations of TG6050 by intravenous route in patients with advanced NSCLC. | Drug: TG6050<br>* Oncolytic Vaccinia virus containing genes encoding the human interleukin 12 (IL-12) and an anti-CTLA4 antibody administered at different dose.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 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 | 
| 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 | 
| Progression-free survival (PFS) | Time from the first TG6050 infusion to documented tumor progression or death due to any cause. | Up to 1 year | 
| Overall survival (OS) | Time from the first TG6050 infusion to death due to any cause. | Up to 1 year | 
| 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 | 
| Molecular responses (MR) | Circulating tumor DNA (ctDNA) levels and changes over time | Up to 1 year |