Adrenal Gland Tumors, Bladder Cancer, Breast Cancer, Cervical Cancers, Colorectal Cancer, Esophageal Cancer, Gastric Cancer, Head and Neck Cancers, Hepatocellular Carcinoma, Lung Cancer, Melanoma, Ovarian Cancer, Pancreatic Cancer, Prostate Cancer, Renal Cell Carcinoma, Sarcoma
Conditions
Keywords
Oncolytic Virus Therapy, Advanced Solid Tumors, Metastatic Cancer, Refractory Cancer, Immunotherapy, Vaccinia Virus
Brief summary
This is a Phase I clinical trial evaluating an investigational treatment called IDOV-Immune, a type of oncolytic virus therapy, for adults with advanced solid tumors that have not responded to standard treatments. Oncolytic viruses are designed to infect and destroy cancer cells and have the potential to stimulate the immune system to fight the tumor. The purpose of this study is to determine the safety of IDOV-Immune, how well it is tolerated, and to identify the highest dose that can be safely given. Researchers will also study how the drug behaves in the body, how the immune system responds to it, and whether it shows any signs of shrinking tumors. Participants will receive a single intravenous (IV) infusion of IDOV-Immune and will be closely monitored for side effects and any changes in their cancer. This study is being conducted at multiple sites in the United States and Australia.
Detailed description
This is a first-in-human (FIH), Phase I, open-label, multi-center clinical trial designed to evaluate IDOV-Immune, an investigational oncolytic vaccinia virus-based immunotherapy, in adult participants with advanced solid tumors who have exhausted standard treatment options. IDOV-Immune is a genetically engineered vaccinia virus designed to selectively infect and destroy tumor cells while enhancing immune responses through the expression of immune-stimulating molecules. It has been further modified to improve tumor selectivity and minimize the risk of harming healthy cells. Study Design: The trial will follow a dose-escalation design to determine the maximum tolerated dose (MTD), the recommended Phase 2 dose (RP2D), and the overall safety and tolerability profile of IDOV-Immune. A Bayesian Optimal Interval (BOIN) design will guide dose-escalation decisions, based on observed dose-limiting toxicities (DLTs) during a 28-day observation period after the initial dose. The study will also assess preliminary signs of antitumor activity at each dose level. IDOV-Immune will be administered as a single intravenous (IV) infusion on Day 1 of a 28-day treatment cycle. Participants will undergo frequent safety assessments, including physical exams, laboratory tests, imaging studies, and immune response monitoring. Pharmacokinetics (how the virus behaves in the body), pharmacodynamics (how the virus impacts immune and tumor-related biomarkers), and immunogenicity (the body's immune response to the virus) will also be evaluated. Planned Enrollment and Cohorts: The study is expected to enroll up to approximately 42 participants in the dose-escalation phase. If appropriate, additional participants may be enrolled in backfill cohorts at selected dose levels to further assess the safety, biomarkers , and preliminary efficacy in specific populations. Across all study parts, total enrollment could reach approximately 78 participants. Study Objectives: The primary objective is to assess the safety and tolerability of IDOV-Immune and to determine the RP2D for future studies. Secondary objectives include evaluating how the investigational product moves through and affects the body (pharmacokinetics and pharmacodynamics), as well as initial signs of tumor response, including objective response rate (ORR), disease control rate (DCR), and progression-free survival (PFS). Rationale: There remains a significant unmet need for effective therapies for patients with advanced solid tumors who have progressed on or are intolerant to standard treatments. Oncolytic viruses have the potential for destroying cancer cells and activating anti-tumor immune responses. IDOV-Immune's multi-pronged design - combining direct oncolysis, immune recruitment, and immune system activation - aims to maximize therapeutic potential while maintaining an acceptable safety profile. Study Locations: The study will be conducted at multiple clinical sites in the United States and Australia with expertise in early-phase oncology trials and oncolytic virus therapies.
Interventions
BIOLOGICALIDOV-Immune (oncolytic vaccinia virus)
IDOV-Immune is a genetically engineered oncolytic vaccinia virus designed to selectively infect and destroy tumor cells while stimulating the immune system. This study investigates IDOV-Immune as a single intravenous infusion in a first-in-human, Phase 1, dose-escalation trial in participants with advanced solid tumors. The dose will escalate based on safety data, with a goal of identifying the recommended Phase 2 dose (RP2D).
Sponsors
ViroMissile, Inc.
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
This is a Phase I, open-label, single-group, dose-escalation study evaluating IDOV-Immune, an investigational oncolytic vaccinia virus, in adults with advanced solid tumors. Participants will receive a single intravenous (IV) infusion, with dose levels adjusted based on safety data using a Bayesian Optimal Interval (BOIN) design. The primary goal is to assess safety, tolerability, and determine the recommended Phase 2 dose (RP2D). Dose-limiting toxicities (DLTs) will be monitored for 28 days after dosing. Following dose escalation, expansion cohorts may be opened at selected doses to further evaluate safety and preliminary antitumor activity.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Age ≥ 18 years. * Histologically or cytologically confirmed advanced solid tumors that have progressed despite standard therapy, or for which no standard therapy exists. * ECOG performance status ≤ 1. * Measurable disease per RECIST v1.1. * Adequate organ and bone marrow function. * At least 28 days since major surgery, prior immunotherapy, or radiotherapy (with exceptions for minor procedures). * Negative pregnancy test for women of childbearing potential. * Agreement to use effective contraception during treatment and for 3 months after. * Ability to provide informed consent and comply with study requirements. Key
Exclusion criteria
* Prior treatment with an oncolytic virus. * Active or recent vaccinia virus infection or smallpox/monkeypox vaccination within 10 years. * Active uncontrolled infection requiring systemic treatment. * History of hepatitis B, hepatitis C, or HIV (unless meeting protocol-specific criteria). * Unresolved ≥ Grade 2 toxicities from prior therapies (except hair loss or stable chronic conditions). * Active or symptomatic autoimmune disease requiring systemic therapy. * Active or untreated CNS metastases (unless stable per protocol). * Significant cardiac disease (e.g., NYHA Class III/IV heart failure). * Interstitial lung disease or prior pneumonitis requiring steroids. * Conditions requiring chronic immunosuppressive therapy. * Severe skin disorders or history of pancreatitis. * Bleeding disorders or history of recent serious thromboembolic events. * Any medical or psychiatric condition that could interfere with study participation.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Dose-Limiting Toxicities (DLTs) | From first dose through the end of the DLT evaluation period (28 days) | The number and proportion of participants experiencing dose-limiting toxicities (DLTs), assessed by dose level during the DLT evaluation period. DLTs are defined per protocol-specified criteria and graded according to CTCAE. |
| Safety and Tolerability of IDOV-Immune by Dose Level | From first dose through end of treatment (28 days) (and/or safety follow-up period as defined in protocol [90 days]) | Incidence, severity, and relationship of treatment-emergent adverse events (TEAEs) by dose level. |
| Determination of the Maximum Tolerated Dose (MTD) | From first dose through completion of dose-escalation cohorts (2 years) | Dose level(s) at which the observed incidence of dose-limiting toxicities meets protocol-defined criteria for maximum tolerated dose determination. |
| Identification of Dose Level(s) for Further Clinical Evaluation | From first dose through completion of dose-escalation and data review (2 years) | Dose level(s) selected for further clinical evaluation based on integrated safety, tolerability, and pharmacokinetic data, as defined in the protocol. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetic Parameters of IDOV-Immune by Dose Level | From first dose through completion of PK sampling (2 years) | Pharmacokinetic parameters including, but not limited to, maximum observed concentration (Cmax), area under the concentration-time curve (AUC), time to maximum concentration (Tmax), and half-life (t½), summarized by dose level. |
| Pharmacodynamic and Biomarker Responses Following IDOV-Immune Administration | From first dose through completion of biomarker assessments (2 years) | Changes in protocol-specified pharmacodynamic and exploratory biomarker endpoints over time, summarized by dose level. |
| Objective Response Rate (ORR) | Up to 12 months | Percentage of participants with a best overall response of complete response (CR) or partial response (PR), assessed per RECIST v1.1. |
| Duration of Response (DOR) | Up to 12 months | Time from first documented objective response (CR or PR) to progression or death. |
| Disease Control Rate (DCR) | Up to 12 months | Proportion of participants achieving CR, PR, or stable disease (SD) lasting at least 8 weeks. |
| Progression-Free Survival (PFS) | Up to 12 months | Time from first dose to documented disease progression or death from any cause. |
| Overall Survival (OS) | Up to 12 months | Time from first dose to death from any cause. |
| Incidence of Neutralizing Antibody Response | Up to 90 days post-treatment | Number of participants who develop detectable anti-vaccinia neutralizing antibodies after IDOV-Immune infusion. |
Countries
Australia, United States
Contacts
CONTACTClinical Development
Outcome results
None listed