NCT07001592

Intra-tumoral (IT) Injection of vvDD-hIL2-2-RG-1 for Metastatic Gastrointestinal and Peritoneal Tumors

A Phase I Dose-Escalation Trial of vvDD-hIL2-2-RG-1 (Vaccina Virus Double Deleted) Administered by Intra-tumoral (IT) Injection for Metastatic Gastrointestinal and Peritoneal Tumors

• Status: Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 18 (estimated)
• Sponsor: Allegheny Singer Research Institute (also known as Allegheny Health Network Research Institute) · Academic / Other
• Sex: All
• Age: 18 Years – 69 Years
• Healthy volunteers: Not accepted

Summary

This research study aims to evaluate the safety and determine the optimal dose of a new experimental drug, vvDD-hIL2 (vaccinia virus double-deleted human interleukin 2), in patients with advanced abdominal cancer. The study will involve three dose levels, with three to six patients enrolled at each level. vvDD-hIL2 is a genetically modified vaccinia virus, derived from the virus previously used for smallpox vaccination. The modification is intended to target and destroy tumors while minimizing harm to healthy tissues by stimulating the body's immune response. Participants will receive an injection of vvDD-hIL2 directly into their abdominal tumors at AHN West Penn. The study team will monitor for side effects and assess tumor response to the treatment. Active participation will last up to two months, involving seven clinic visits and approximately four lab visits at AHN West Penn Hospital. Visits will include standard of care procedures as well as study-specific tests and exams. Most visits will last one to two hours, with some extending to two to three hours. The drug administration day will require a twelve-hour visit. Effectiveness and side effects will be evaluated through blood draws, oral swabs, urinalysis and tissue biopsies. Tissue samples will be used for genomic analysis and stored for potential future research. Data collected may also be used for future research purposes. Previous human trials of vvDD-hIL2 have reported side effects such as pain, rash or inflammation at the injection site, low-grade fevers, flu-like symptoms, and fatigue. There is a rare risk of rash transmission to close contacts with skin openings, and information on limiting contact and managing rash development will be provided.

Detailed description

This is a Phase I, open-label, single dose, dose-escalation trial in subjects with metastatic gastrointestinal tumors who have failed standard systemic chemotherapy or immunotherapy. Gastrointestinal tumors include esophageal cancer (EC), gastric cancer (GC), colon cancer (CC), rectal cancer (RC), liver cancer (LC), and pancreatic cancer (PC) The vvDD-IL-2 virus was designed to activate T-cells with a goal to reduce systemic toxicity while optimizing immune clearance of tumors following intraperitoneal delivery. Utilizing a platform of a thymidine kinase (tk) and vaccinia growth factor (vgf) deleted oncolytic Western Reserve (WR) strain vaccinia virus (vvDD), vvDD-IL-2 variants have been designed to deliver membrane bound IL-2 into the tumor microenvironment. All subjects who have refractory tumors will receive the virus at one of the three dose levels in a single dose sequential dose modified toxicity probability interval (mTPI) design. Eligible subjects will receive one needle injection (per tumor) of vvDD-hIL-2-RG-1. A minimum of 28 days observation period must pass after injection of the first subject in each level without experiencing a dose-limiting toxicity (DLT) before administering/injecting the second patient at that dose level. A new dose level will not be initiated until the completion of the 28-day observation period from the administration of the previous dose level.

Conditions

• Gastric Neoplasms
• Esophageal Cancer
• Liver Cancer
• Liver Metastasis
• MSS-CRC
• MSS
• Gastric Adenocarcinoma
• Peritoneal Cancer
• Peritoneal Carcinoma
• Peritoneal Metastases
• MSI-H
• Gastric Cancer

Interventions

Type	Name	Description
BIOLOGICAL	vvDD-hIL-2-RG-1	A single dose of the investigational agent will be injected intratumorally at one of the following three dose levels. Level 1: 3 x 108 p.f.u. Level 2: 1 x 109 p.f.u. Level 3: 3 x 109 p.f.u. p.f.u = Plaque-forming unit(s) Dose will be escalated in cohorts of 3, according to a standard 3+3 design.

Timeline

• Start date: 2025-05-06
• Primary completion: 2028-04-01
• Completion: 2028-05-01
• First posted: 2025-06-03
• Last updated: 2025-06-03

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study