Cervical Cancer, Cutaneous Squamous Cell Carcinoma (CSCC), Head and Neck Squamous Cell Carcinoma, Kidney Cancer, Melanoma Stage IV, Merkel Cell Carcinoma of Skin, Mesothelioma, Microsatellite Stable Colorectal Cancer, Non-small Cell Lung Cancer, Renal Cell Carcinoma, Solid Tumor, Adult, Squamous Cell Carcinoma, Urothelial Carcinoma Bladder
Conditions
Brief summary
VET3-TGI is an oncolytic immunotherapy designed to treat advanced cancers. VET3-TGI has not been given to human patients yet, and the current study is designed to find a safe and effective dose of VET3-TGI when administered by direct injection into tumor(s) (called an intratumoral injection) or when given intravenously (into the vein) both alone and in combination with atezolizumab in patients with solid tumors (STEALTH-001).
Detailed description
VET3-TGI was changed in a laboratory to infect and kill cancer cells, leaving healthy cells alone. This is a Phase 1 dose escalation (and expansion) study with VET3-TGI administered by direct injection into tumor(s) or by intravenous infusion. The dose escalation has 4 groups: the first group (Group A) will determine the highest tolerated dose of VET3-TGI when injected into tumor(s); the second group (Group C) will determine the highest tolerated dose of VET3-TGI when infused into the vein. The third and fourth groups (Group B and D) will combine VET3-TGI with atezolizumab. These groups will begin at the highest tolerated dose determined in Group B and Group D, respectively. Once the highest tolerated dose is found for each of these groups, that dose may be expanded to up to 15 additional patients to better examine the efficacy of VET3-TGI.
Interventions
DRUGVET3-TGI
Oncolytic vaccinia virus engineered with immunomodulatory transgenes
DRUGAtezolizumab
anti-pd-L1 antibody
Sponsors
KaliVir Immunotherapeutics
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Have pathologically confirmed, advanced, unresectable, or metastatic solid tumors. Preferred indications include, but are not limited to, breast carcinoma, bladder carcinoma, cervical squamous carcinoma, colorectal carcinoma, esophageal carcinoma, head and neck squamous carcinoma, renal cell carcinoma, ovarian carcinoma, sarcoma, thymoma, and uterine carcinoma. * Failed, intolerant to, or refused potentially curative treatment options, including but not limited to, standard of care molecularly targeted agents, immunotherapy (e.g., anti -pembrolizumab/PDL1 antibodies), and chemotherapy * Measurable disease as per RECIST 1.1 criteria * At least one tumor amenable to safe ITu injections and/or biopsies * ECOG performance status 0 or 1 * Demonstrate adequate organ function * Must be willing to comply with all protocol procedures and adhere to post-treatment care instructions Additional Inclusion criteria exist Key
Exclusion criteria
* Prior systemic therapy washout (dependent upon the therapy) * Requires use of anti-platelet or anti-coagulant therapy that cannot be safely suspended for per protocol biopsies or intra-tumoral injections. * CNS metastases and/or carcinomatous meningitis that have not been completely resected or completely irradiated. * Prior history of myocarditis * Known HIV/AIDS, active HBV or HCV infection. * Receiving high dose immunosuppressive medication or has a significant immunodeficiency (e.g. transplant recipient, etc). Additional
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of adverse events with VET3-TGI alone or in combination with atezolizumab | 108 months | Percentage of patients with adverse events by grade as determined by NCI CTCAE v5.0 |
| Incidence of dose limiting toxicities reported with VET3-TGI alone or in combination with atezolizumab | 4 weeks | Number of dose limiting toxicities, as defined in the protocol, by dose group |
| Determine the recommended Phase 2 dose | 4 weeks | he highest dose of VET3-TGI in each group that can be administered where fewer than 2 patients have a dose-limiting safety event alone or when combined with atezolizumab as assessed by NCI CTCAE v.5.0 during the Phase 1 dose escalation |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Efficacy assessment: overall response rate (ORR) | 108 months | The number and proportion of patients with a partial response (PR) or complete response (CR) on imaging by RECIST 1.1 |
| Efficacy assessment: Duration of response (DOR) | 108 months | Median duration of response in patients with a CR or PR |
| Efficacy assessment: disease control rate (DCR) | 108 months | The number and proportion of patients with stable disease (SD), or a partial response (PR) or complete response (CR) on imaging by RECIST 1.1 |
| Efficacy assessment: Time to tumor progression (TTP) | 108 months | Median time until patient disease progression (PD) |
| Efficacy assessment: Progression free survival (PFS) | 108 months | Median duration of progression free survival of subjects |
| Overall survival | 108 months | median duration of survival across all subjects |
| Immune changes in tissue and blood | 6 weeks | number of subject tissue samples with immune cell infiltrates and heat map changes in the molecular signature of tissue samples |
| VET3-TGI delivery and replication kinetics | 6 weeks | Number of subject tissues with positive VET3-TGI gene signatures denoting delivery and complete replication of VET3-TGI |
Countries
United States
Contacts
CONTACTAdina Pelusio
CONTACTJames Burke, MD
Outcome results
None listed