Advanced Solid Tumor, Breast Cancer, Esophagus Cancer, HNSCC, Non-melanoma Skin Cancer, NSCLC, Sarcoma
Conditions
Keywords
Oncolytic virus, Herpes virus
Brief summary
A Phase I/IIa Study of the Safety and Tolerability of T3011 Administered via Intratumoral Injection in Patients with Advanced Solid Tumors
Detailed description
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.
Interventions
BIOLOGICALT3011
T3011 will be administered through intratumoral injection in patients with advanced solid tumors.
Sponsors
ImmVira Pharma Co. Ltd
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. | Up to 2 years from first dose of T3011 | Incidence rate of TEAE; Incidence rate of DLT |
| 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. | Up to 2 years from first dose of T3011 | Incidence rate of TEAE; |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| In part I and part II, Characteristics of biological distribution and biological effect of single dose and multiple dose IT T3011. | Up to 2 years from first dose of T3011 | The changes of PD-1 and IL-12 concentration after administration |
| In part I and part II, Evaluation of pharmacodynamics of T3011 | Up to 2 years from first dose of T3011 | IFN-γ、 IL-1β、 IL-2、 IL-4、 IL-6、 IL-8、 IL-10、 IL-13、 TNF-α |
| Overall response rate (ORR) | Up to 2 years from first dose of T3011 | 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. |
| In part I and part II, Evaluation of immunogenicity of T3011 | Up to 2 years from first dose of T3011 | ADAs and Nabs of IL-12, anti-PD-1 antibody and HSV-1 |
| Duration of response (DOR) | Up to 2 years from first dose of T3011 | 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. |
| Progression-free survival (PFS) | Up to 2 years from first dose of T3011 | 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. |
| In part III,Overall Survival (OS) | Up to 2 years from first dose of T3011 | OS is defined as the time from enrollment to death from any cause. |
| Disease control rate (DCR) | Up to 2 years from first dose of T3011 | 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| In part II and part III,Exploring the relationship between genetic changes and drug efficacy | Up to 2 months from first dose of T3011 | Genetic testing of tumor tissue |
| In part II and part III,Exploring tumor immunomodulatory mechanism and histological changes after IT T3011 | Up to 2 months from first dose of T3011 | Assesse histological changes by immunohistochemical fluorescence detection |
| In part II and part III,Exploring the proliferation and activity of immune cells in blood after IT T3011 | Up to 2 years from first dose of T3011 | Analysis of immune cells in blood |
Countries
China
Contacts
Primary ContactImmVira Pharma Co. LTD
Outcome results
None listed