Clinical trial NCT06910657: IDOV-Immune for Advanced Solid Tumors
Official title: A First-in-human, Phase I, Multi-center, Open-label, Dose-escalation Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Preliminary Evidence of Antitumor Activity of IDOV-Immune in Adult Participants With Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE1
Conditions: Colorectal Cancer
Pancreatic Cancer
Melanoma
Ovarian Cancer
Gastric Cancer
Esophageal Cancer
Hepatocellular Carcinoma
Renal Cell Carcinoma
Breast Cancer
Sarcoma
Bladder Cancer
Lung Cancer
Prostate Cancer
Cervical Cancers
Head and Neck Cancers
Adrenal Gland Tumors
Keywords: Oncolytic Virus Therapy
Advanced Solid Tumors
Metastatic Cancer
Refractory Cancer
Immunotherapy
Vaccinia Virus
Lead sponsor: ViroMissile, Inc.
Sponsor class: INDUSTRY
First posted: 2025-04-04
Enrollment: 78
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
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.
Primary purpose: TREATMENT

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.

Eligibility 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.

Primary outcomes:
measure: Incidence of Dose-Limiting Toxicities (DLTs)
timeFrame: First 28 days after treatment (Cycle 1)
measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
timeFrame: Up to 90 days post-treatment
measure: Determination of Maximum Tolerated Dose (MTD)
timeFrame: Through completion of dose-escalation phase (~24 months)
measure: Determination of Recommended Phase 2 Dose (RP2D)
timeFrame: Through completion of dose-escalation and evaluation of all safety, PK/PD, and clinical activity data (~24 months)
Secondary outcomes:
measure: Peak Whole Blood Viral Genome Copy Number
timeFrame: Up to 28 days post-infusion
measure: Peak Serum Cytokine (IL-12 and CXCL9) Concentration
timeFrame: Up to 28 days post-infusion
measure: Serum Cytokine (IFN-β, IFN-γ, IL-1β, IL-6, IL-10, TNF-α, and TGF-β1) Concentration
timeFrame: Up to 28 days post-infusion
measure: Objective Response Rate (ORR)
timeFrame: Up to 12 months
measure: Duration of Response (DOR)
timeFrame: Up to 12 months
measure: Disease Control Rate (DCR)
timeFrame: Up to 12 months
measure: Progression-Free Survival (PFS)
timeFrame: Up to 12 months
measure: Overall Survival (OS)
timeFrame: Up to 12 months
measure: Incidence of Neutralizing Antibody Response
timeFrame: Up to 90 days post-treatment
Other outcomes:
Locations:
city: St. Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: San Antonio
country: United States
facility: South Texas Accelerated Research Therapeutics
state: Texas
city: Westmead
country: Australia
facility: Westmead Hospital
state: New South Wales
city: Melbourne
country: Australia
facility: The Alfred Hospital
state: Victoria
Study officials:
References: