A Study of VET3-TGI in Patients With Solid Tumors

Non-small Cell Lung Cancer Clinical Trial

— STEALTH-001  

Official title:

A Phase 1/1b Study of VET3-TGI Administered Alone and in Combination With Pembrolizumab in Patients With Advanced Solid Tumors

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06444815
• Other study ID #: STEALTH-001
• Status: Not yet recruiting
• Phase: Phase 1
• Start date: August 1, 2024
• Est. completion date: December 31, 2027

Study information

• Verified date: May 2024
• Source: KaliVir Immunotherapeutics
• Contact: Adina Pelusio
• Phone: +13057722084
• Email: clinops[@]kalivir.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 60
• Est. completion date: December 31, 2027
• Est. primary completion date: September 30, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 Exclusion criteria exist

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Merkel Cell
• Carcinoma, Renal Cell
• Cervical Cancer
• Head and Neck Squamous Cell Carcinoma
• Kidney Cancer
• Kidney Neoplasms
• Melanoma Stage IV
• Mesothelioma
• Microsatellite Stable Colorectal Cancer
• Non-small Cell Lung Cancer
• Renal Cell Carcinoma
• Solid Tumor, Adult
• Squamous Cell Carcinoma of Head and Neck

Intervention

Drug:
• VET3-TGI
Oncolytic vaccinia virus engineered with immunomodulatory transgenes
• Pembrolizumab
anti-pd1 antibody

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
KaliVir Immunotherapeutics

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence 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	108 months
Primary	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	4 weeks
Primary	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	4 weeks
Secondary	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	108 months
Secondary	Efficacy assessment: Duration of response (DOR)	Median duration of response in patients with a CR or PR	108 months
Secondary	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	108 months
Secondary	Efficacy assessment: Time to tumor progression (TTP)	Median time until patient disease progression (PD)	108 months
Secondary	Efficacy assessment: Progression free survival (PFS)	Median duration of progression free survival of subjects	108 months
Secondary	Overall survival	median duration of survival across all subjects	108 months
Secondary	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	6 weeks
Secondary	VET3-TGI delivery and replication kinetics	Number of subject tissues with positive VET3-TGI gene signatures denoting delivery and complete replication of VET3-TGI	6 weeks