A Study of VET3-TGI in Patients With Solid Tumors

Phase 1

Recruiting

• Conditions: Microsatellite Stable Colorectal Cancer; Head and Neck Squamous Cell Carcinoma; Merkel Cell Carcinoma of Skin; Mesothelioma; Solid Tumor, Adult; Cervical Cancer; Renal Cell Carcinoma; Kidney Cancer; Melanoma Stage IV; Non-small Cell Lung Cancer
• Interventions: Drug: VET3-TGI; Drug: Pembrolizumab

• Registration Number: NCT06444815
• Lead Sponsor: KaliVir Immunotherapeutics

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 pembrolizumab 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 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 Timeline

• Study First Submitted: 2024-05-30
• Study First Submitted QC: 2024-05-30
• Study First Posted: 2024-06-06
• Study Start: 2024-09-16
• Status Verified: 2024-12
• Last Update Submitted: 2024-12-09
• Last Update Posted: 2024-12-11
• Primary Completion: 2027-09-30
• Study Completion: 2027-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 60

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

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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 Exclusion criteria exist

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Group B: VET3-TGI intratumoral in combination with pembrolizumab	VET3-TGI	VET3-TGI will be given in combination with pembrolizumab at the highest tolerated dose from Group A. Pembrolizumab will be administered via intravenous (IV) infusion for up to 2 years.
Group B: VET3-TGI intratumoral in combination with pembrolizumab	Pembrolizumab	VET3-TGI will be given in combination with pembrolizumab at the highest tolerated dose from Group A. Pembrolizumab will be administered via intravenous (IV) infusion for up to 2 years.
Group D: VET3-TGI intravenous in combination with pembrolizumab	VET3-TGI	VET3-TGI will be given in combination with pembrolizumab at the highest tolerated dose from Group C. Pembrolizumab will be administered via intravenous (IV) infusion for up to 2 years.
Group A: VET3-TGI alone intratumoral	VET3-TGI	Dose escalation of VET3-TGI alone administered by direct injection into tumor(s) x 4. Booster injections of VET3-TGI are permitted for up to 2 years.
Group C: VET3-TGI alone intravenous	VET3-TGI	Dose escalation of VET3-TGI alone administered by IV infusion x 6. Booster infusions of VET3-TGI are permitted for up to 2 years.
Group D: VET3-TGI intravenous in combination with pembrolizumab	Pembrolizumab	VET3-TGI will be given in combination with pembrolizumab at the highest tolerated dose from Group C. Pembrolizumab will be administered via intravenous (IV) infusion for up to 2 years.

Primary Outcome Measures

Name	Time	Method
Incidence of dose limiting toxicities reported with VET3-TGI alone or in combination with pembrolizumab	4 weeks	Number of dose limiting toxicities, as defined in the protocol, by dose group
Incidence of adverse events with VET3-TGI alone or in combination with pembrolizumab	108 months	Percentage of patients with adverse events by grade as determined by NCI CTCAE v5.0
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 pembrolizumab as assessed by NCI CTCAE v.5.0 during the Phase 1 dose escalation

Secondary Outcome Measures

Name	Time	Method
Efficacy assessment: Duration of response (DOR)	108 months	Median duration of response in patients with a CR or PR
Efficacy assessment: Time to tumor progression (TTP)	108 months	Median time until patient disease progression (PD)
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
Overall survival	108 months	median duration of survival across all subjects
Efficacy assessment: Progression free survival (PFS)	108 months	Median duration of progression free survival of 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
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

Trial Locations

Locations (4)

USC/Norris Comprehensive Cancer Center; 🇺🇸 Los Angeles, California, United States

Community Health Network; 🇺🇸 Indianapolis, Indiana, United States

Mary Crowley Cancer Research; 🇺🇸 Dallas, Texas, United States

University of Texas MD Anderson Cancer Center; 🇺🇸 Houston, Texas, United States