Direct injection of a modified vaccinia virus (vvDD-hIL2) into abdominal and gastrointestinal 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

This trial will try a single direct injection of a modified vaccinia virus (vvDD-hIL2) into abdominal tumors to see if it is safe for adults with advanced metastatic gastrointestinal or peritoneal cancers who have not responded to standard treatments.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 18 (estimated)
• Ages: 18 Years to 69 Years
• Sex: All
• Sponsor: Allegheny Singer Research Institute (also known as Allegheny Health Network Research Institute) (Academic / other)
• Drugs / interventions: chemotherapy, immunotherapy, radiation
• Locations: 1 site (Pittsburgh, Pennsylvania)
• Trial ID: NCT07001592 on ClinicalTrials.gov

What this trial studies

This is a Phase 1, open-label, dose-escalation trial testing intratumoral or intraperitoneal delivery of vvDD-hIL2, a genetically modified vaccinia virus engineered to express membrane-bound IL-2. Patients with refractory metastatic gastrointestinal or peritoneal tumors will receive a single needle injection per tumor at one of three dose levels, using a sequential modified toxicity probability interval design. Three to six patients will be treated per dose level with at least a 28-day observation period for dose-limiting toxicities before escalation. Safety, tolerability, and preliminary tumor response will be monitored through clinic and lab visits at AHN West Penn Hospital.

Who should consider this trial

Good fit: Adults aged 18 to under 70 with histologically confirmed metastatic gastrointestinal or peritoneal tumors who have failed standard systemic chemotherapy (and systemic immunotherapy if MSI-H), have Karnofsky Performance Status >70, and adequate organ and bone marrow function are the intended candidates.

Not a fit: Patients who are critically ill, have poor performance status, inadequate organ or bone marrow function, active uncontrolled infections, or who are pregnant or breastfeeding are unlikely to be eligible or to benefit from this trial.

Why it matters

Potential benefit: If successful, the approach could stimulate a local anti-tumor immune response that helps shrink tumors while limiting systemic side effects compared with some systemic immunotherapies.

How similar studies have performed: Early-phase trials of oncolytic vaccinia viruses and IL-2–armed oncolytic platforms have shown promising safety and immune-activation signals but have not yet produced definitive, broadly applicable clinical benefits.

Eligibility criteria

Inclusion Criteria:

1. Males or females age, 18 to \< 70 years at the time of consent
2. Histologically confirmed metastases from gastrointestinal tumors with molecular determinants for MSI and KRAS.
3. For microsatellite stable (MSS) tumors, subjects must have failed (or be ineligible for) standard 1st and 2nd line chemotherapy. For microsatellite instability-high (MSI-H) tumors, subjects must also have failed (or be ineligible for) systemic immunotherapy.
4. Karnofsky Performance Status (KPS) of \> 70
5. Anticipated survival of at least 12 weeks.
6. Written informed consent in accordance with national, local, and institutional guidelines obtained prior to any study procedures (subject or subject's legally authorized representative (LAR) must have the ability to understand and willingness to sign a written informed consent).
7. Adequate bone marrow function: WBC \> 2,000 and \<50,000 cells/mm3, ANC \> 1,000 cells/mm3, hemoglobin \>8 g/dL, and platelet count \>100,000 cells/mm3.
8. Adequate renal function: serum creatinine level ≤ 2xULN
9. Adequate liver function: Serum bilirubin \< 1.5 x ULN
10. Acceptable coagulation status: INR \< ULN +15%. All patients must be able to suspend anticoagulant therapy for study specific biopsies and intra-tumoral injection.
11. Women of childbearing potential (defined as all women physiologically capable of becoming pregnant) must have negative serum or urine pregnancy test.
12. If sexually active, to prevent pregnancy and to prevent the spread of virus, subject must use an acceptable method of contraception as well as barrier contraception from screening through 6 weeks following study treatment with vvDD-hIL-2-RG-1.
13. Subjects must be willing to comply with all study procedures, requirements, adhere to post-treatment care instructions and follow-up examinations.
14. Have measurable disease based on RECIST 1.1 criteria.
15. Have at least one tumor at least 1 cm in diameter amenable to safe intra-tumoral injection.

Exclusion Criteria:

1. Pregnant or nursing an infant.
2. Systemic corticosteroid or other immunosuppressive medication use within 2 weeks of the study treatment.
3. Significant immunodeficiency (e.g. due to underlying illness and/or medication) in subject or household contacts (must be able to avoid household contact with immunodeficient person for 3 weeks).
4. Clinically significant active infection or uncontrolled medical condition (e.g., pulmonary, neurological, cardiovascular, gastrointestinal, genitourinary) considered high risk for investigational new drug treatment, per investigator discretion.
5. Active eczema or psoriasis or other inflammatory skin conditions
6. Unstable cardiac disease which includes but is not limited to any of the following within 6 months prior to study entry: myocardial infarction (MI), unstable angina, congestive heart failure, myocarditis, ventricular arrhythmias diagnosed and requiring medication.

   * New York Heart Association functional class III-IV heart failure on active treatment
   * Pulse oximetry of \< 90% in room air at rest
7. Subjects who have received radiation, chemotherapy or other potentially immunosuppressive therapy within 2 weeks prior to study screening and within 4 weeks prior to anticipated vvDD-hIL-2-RG-1 treatment.
8. Experienced a severe systemic reaction or side-effect as a result of a previous smallpox vaccination.
9. Subjects who, in the opinion of the Investigator, have a medical condition that would subject the subject to prohibitive risk by participation in this study, or who may be unable to safely complete the required tumor biopsies.
10. Subjects with household contacts who are children \< 5 years old, have active eczema, psoriasis or other inflammatory skin conditions or have a significant immunodeficiency due to underlying illness (e.g. human immunodeficiency virus) and/or medication (e.g. systemic corticosteroids) will be excluded unless alternate living arrangements can be made during the subject's active dosing period and for three weeks following the study medication.
11. Vaccination with a live virus in the previous 60 days prior to Day 0.
12. Inability or unwillingness to give informed consent.
13. Is unable or unwilling to comply with protocol follow-up requirements. -

Where this trial is running

Pittsburgh, Pennsylvania

• AHN West Penn Hospital — Pittsburgh, Pennsylvania, United States (Recruiting)

Study contacts

• Principal investigator: Patrick Wagner, MD — Allegheny Health Network
• Study coordinator: Patrick Wagner, MD

Conditions Gastric Neoplasms; Esophageal Cancer; Liver Cancer; Liver Metastasis; MSS-CRC; MSS; Gastric Adenocarcinoma; Peritoneal Cancer