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 pembrolizumab in patients with solid tumors (STEALTH-001).
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 pembrolizumab. 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.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
60
Oncolytic vaccinia virus engineered with immunomodulatory transgenes
anti-pd1 antibody
USC/Norris Comprehensive Cancer Center
Los Angeles, California, United States
RECRUITINGUC Irvine Health
Orange, California, United States
RECRUITINGUniversity of Miami
Miami, Florida, United States
RECRUITINGCommunity Health Network
Indianapolis, Indiana, United States
RECRUITINGUPMC- Hillman Cancer Center
Pittsburgh, Pennsylvania, United States
RECRUITINGMary Crowley Cancer Research
Dallas, Texas, United States
RECRUITINGUniversity of Texas MD Anderson Cancer Center
Houston, Texas, United States
RECRUITINGIncidence of adverse events with VET3-TGI alone or in combination with pembrolizumab
Percentage of patients with adverse events by grade as determined by NCI CTCAE v5.0
Time frame: 108 months
Incidence of dose limiting toxicities reported with VET3-TGI alone or in combination with pembrolizumab
Number of dose limiting toxicities, as defined in the protocol, by dose group
Time frame: 4 weeks
Determine the recommended Phase 2 dose
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 pembrolizumab as assessed by NCI CTCAE v.5.0 during the Phase 1 dose escalation
Time frame: 4 weeks
Efficacy assessment: overall response rate (ORR)
The number and proportion of patients with a partial response (PR) or complete response (CR) on imaging by RECIST 1.1
Time frame: 108 months
Efficacy assessment: Duration of response (DOR)
Median duration of response in patients with a CR or PR
Time frame: 108 months
Efficacy assessment: disease control rate (DCR)
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
Time frame: 108 months
Efficacy assessment: Time to tumor progression (TTP)
Median time until patient disease progression (PD)
Time frame: 108 months
Efficacy assessment: Progression free survival (PFS)
Median duration of progression free survival of subjects
Time frame: 108 months
Overall survival
median duration of survival across all subjects
Time frame: 108 months
Immune changes in tissue and blood
number of subject tissue samples with immune cell infiltrates and heat map changes in the molecular signature of tissue samples
Time frame: 6 weeks
VET3-TGI delivery and replication kinetics
Number of subject tissues with positive VET3-TGI gene signatures denoting delivery and complete replication of VET3-TGI
Time frame: 6 weeks
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