A Study of T3011 Administered Via Intratumoral Injection in Patients With Advanced Solid Tumors

Study Overview
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Brief Summary
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A Phase I/IIa Study of the Safety and Tolerability of T3011 Administered via Intratumoral Injection in Patients with Advanced Solid Tumors

Detailed Description
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This is a Phase I/IIa, open-label, first-in-human study of T3011 given via intratumoral (IT) injection in participants with advanced or metastatic solid tumors. Part I and part II of the study is a dose escalation which will use a 3+3 design to evaluate escalating doses of T3011. Part I is a single dose escalation. Part II is multiple dose escalation. Total enrollment will depend on the toxicities and/or activity observed, with approximately 8-48 evaluable participants enrolled. Once the RP2D is established ,Part III will enroll approximately 40-60 participants with sarcoma , approximately 10-25 participants with Malignant head and neck tumor,approximately 10-25 participants with breast cancer,approximately 10-25 participants with esophagus cancer,approximately 10-25 participants with lung cancer and approximately 10-25 participants with non-melanoma skin cancer.

Official Title
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A Phase I/IIa Study to Assess the Safety, Tolerability, Biodistribution and Pharmacodynamic of T3011 Herpes Virus Administered Via Intratumoral Injection in Patients With Advanced Solid Tumors.

Conditions
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Advanced Solid Tumor, Sarcoma, HNSCC, Breast Cancer, Esophagus Cancer, NSCLC, Non-melanoma Skin Cancer

Intervention / Treatment
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* Biological: T3011
* Biological: T3011
* Biological: T3011
* Biological: T3011
* Biological: T3011
* Biological: T3011
* Biological: T3011


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 1. Age 18 70 years Part I ; Age 18 years or older (Part II and III ). 2. Histologically or pathologically confirmed diagnosis of locally recurrent or metastatic advanced malignancy. 3. Measurable disease per RECIST version 1.1. 4. Must have at least 1 tumor lesion that is accessible for IT injection of T3011 in the opinion of the investigator. 5. Eastern Cooperative Oncology Group (ECOG) performance status 0-1. 6. Life expectancy > 12 weeks. 7. Women of child-bearing potential (WCBP) and men must agree to use adequate contraception prior to study entry, while on study treatment, and for six months after receiving last dose of T3011. 8. WCBP must have a negative serum pregnancy test Within 7 days prior to W1D1. 9. Capable of understanding and complying with protocol requirements. Exclusion Criteria: 1. Last dose of previous anticancer therapy < 4 weeks. 2. Prior treatment with another oncolytic virus or gene therapy. 3. Previous intolerance to anti-PD-(L)1 monoclonal antibody or previous history of immunotherapy induced non-infectious pneumonitis/interstitial lung disease. 4. History of seizure disorders within 12 months of Screening. 5.History of allergic reactions attributed to compounds of similar biological composition to HSV-1, IL-12, or anti-PD-1 monoclonal antibody. 6. Requires continued concurrent therapy with any drug active against HSV. 7. Pregnant or lactating.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: T3011 Herpes Virus Injection<br> | Biological: T3011<br>* T3011 will be administered through intratumoral injection in patients with advanced solid tumors.<br>Biological: T3011<br>* T3011 will be administered through intratumoral injection in patients with sarcoma.<br>Biological: T3011<br>* T3011 will be administered through intratumoral injection in patients with Malignant head and neck tumor.<br>Biological: T3011<br>* T3011 will be administered through intratumoral injection in patients with breast cancer.<br>Biological: T3011<br>* T3011 will be administered through intratumoral injection in patients with esophagus cancer.<br>Biological: T3011<br>* T3011 will be administered through intratumoral injection in patients with lung cancer.<br>Biological: T3011<br>* T3011 will be administered through intratumoral injection in patients with non-melanoma skin cancer.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| In part I and part II, Evaluate the safety and tolerability of escalating doses of single dose and multiple dose IT T3011.Characterize DLTs and identify the MTD of IT T3011. | Incidence rate of TEAE; Incidence rate of DLT | Up to 2 years from first dose of T3011 | 
| In part III, Evaluate the safety of multiple dose IT T3011 in the following indications,including sarcoma, Malignant head and neck tumor, breast cancer, esophagus cancer, lung cancer and non-melanoma skin cancer. | Incidence rate of TEAE; | Up to 2 years from first dose of T3011 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| In part I and part II, Characteristics of biological distribution and biological effect of single dose and multiple dose IT T3011. | The changes of PD-1 and IL-12 concentration after administration | Up to 2 years from first dose of T3011 | 
| In part I and part II, Evaluation of pharmacodynamics of T3011 | IFN-γ、 IL-1β、 IL-2、 IL-4、 IL-6、 IL-8、 IL-10、 IL-13、 TNF-α | Up to 2 years from first dose of T3011 | 
| In part I and part II, Evaluation of immunogenicity of T3011 | ADAs and Nabs of IL-12, anti-PD-1 antibody and HSV-1 | Up to 2 years from first dose of T3011 | 
| Overall response rate (ORR) | ORR is defined as the proportion of participants who have a partial response (PR) or complete response (CR) to intervention, based on assessments by RECIST v1.1 and iRECIST. | Up to 2 years from first dose of T3011 | 
| Disease control rate (DCR) | DCR is defined as the percentage of participants who have achieved CR, PR, or stable disease (SD) based on assessments by RECIST v1.1 and iRECIST. | Up to 2 years from first dose of T3011 | 
| Duration of response (DOR) | DOR is defined as the time from the first met CR or PR until disease progression or death due to any cause, whichever occurs first. | Up to 2 years from first dose of T3011 | 
| Progression-free survival (PFS) | PFS is defined as the time from enrollment to the first documentation of progressive disease (PD) or death from any cause, whichever occurs first per RECIST v1.1 and iRECIST. | Up to 2 years from first dose of T3011 | 
| In part III,Overall Survival (OS) | OS is defined as the time from enrollment to death from any cause. | Up to 2 years from first dose of T3011 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Oncolytic virus, Herpes virus