IDOV-Immune for Cancer

Recruiting at 4 trial locations

Overseen By Clinical Develoopment

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: ViroMissile, Inc.

Must not be taking: Immunosuppressants, Steroids

Disqualifiers: Hepatitis, HIV, Cardiac disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 28 days

78 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you are on medications for active infections, autoimmune diseases, or require chronic immunosuppressive therapy, you may not be eligible to participate.

What data supports the effectiveness of the IDOV-Immune treatment for cancer?

Research on a similar treatment combining an immune-modulatory vaccine targeting IDO and PD-L1 with nivolumab in metastatic melanoma showed promising results, with an 80% response rate and 43% complete responses. This suggests that targeting IDO and PD-L1 can be effective in enhancing the immune system's ability to fight cancer. ^{1 2 3 4 5}

What safety data exists for IDOV-Immune or similar treatments?

Immune checkpoint inhibitors, like IDOV-Immune, can cause immune-related side effects such as colitis (inflammation of the colon), hepatitis (liver inflammation), and myocarditis (heart inflammation). These treatments can also trigger autoimmune diseases, where the immune system attacks normal tissues. Managing these side effects often requires a team of specialists to ensure patient safety. ^{6 7 8 9 10}

How does the IDOV-Immune treatment differ from other cancer treatments?

IDOV-Immune is unique because it targets the enzyme indoleamine 2,3-dioxygenase (IDO), which is involved in creating an immunosuppressive environment that helps tumors evade the immune system. By inhibiting IDO, this treatment aims to enhance the effectiveness of other immunotherapies, potentially overcoming resistance to immune checkpoint blockers. ^{2 5 11 12 13}

Eligibility Criteria

Adults with advanced solid tumors, such as various cancers (sarcoma, bladder, lung, prostate, renal cell carcinoma and more), that haven't improved with standard treatments can join. Specific eligibility details are not provided.

Inclusion Criteria

Agreement to use effective contraception during treatment and for 3 months after

Ability to provide informed consent and comply with study requirements

Measurable disease per RECIST v1.1

Exclusion Criteria

I am currently fighting an infection that needs treatment.

Any medical or psychiatric condition that could interfere with study participation

I do not have active or untreated brain metastases.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single intravenous (IV) infusion of IDOV-Immune on Day 1 of a 28-day treatment cycle, with frequent safety assessments and monitoring

28 days

Multiple visits for safety assessments and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment, including progression-free survival and overall survival

Up to 12 months

Dose Escalation

Participants are enrolled in cohorts to determine the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) through a dose-escalation design

Up to 24 months

Treatment Details

Interventions

• IDOV-Immune

Trial Overview The trial is testing IDOV-Immune, an oncolytic virus therapy given via IV infusion to destroy cancer cells and possibly boost the immune system's response against tumors. It aims to find the safest high dose and observe how it affects the body and cancer.

Participant Groups

Group I: IDOV-Immune Dose Escalation Arm Experimental Treatment 1 Intervention

Participants in this arm will receive a single intravenous (IV) infusion of IDOV-Immune, an investigational oncolytic vaccinia virus, on Day 1 of a 28-day treatment cycle. The study will follow a dose-escalation design, with each successive cohort receiving an increased dose based on safety data and observed dose-limiting toxicities (DLTs). Following dose escalation, expansion cohorts may be enrolled at selected dose levels to further assess safety and preliminary antitumor activity.

Who Is Running the Clinical Trial?

ViroMissile, Inc.

Lead Sponsor

Findings from Research

In cohort A, which included 30 patients with metastatic melanoma, the combination of an IDO/PD-L1 vaccine and nivolumab resulted in an impressive overall response rate of 80%, with 50% achieving a complete response and a median progression-free survival of 25.5 months.

Cohort B, where the vaccine was added to patients already on anti-PD-1 therapy, showed limited efficacy with only stable disease in 2 out of 10 patients and a median progression-free survival of just 2.4 months, indicating that the combination may not be effective for those with progressive disease during anti-PD-1 treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term follow-up of anti-PD-1 naïve patients with metastatic melanoma treated with IDO/PD-L1 targeting peptide vaccine and nivolumab. Lorentzen, CL., Kjeldsen, JW., Ehrnrooth, E., et al.[2023]

In a phase 1/2 study involving 30 patients with metastatic melanoma, the combination of the immune-modulatory vaccine (IO102/IO103) with nivolumab showed a high objective response rate of 80%, with 43% of patients achieving complete responses.

The safety profile of the combination therapy was comparable to nivolumab alone, and after a median follow-up of nearly 23 months, the median progression-free survival was 26 months, indicating promising efficacy and tolerability for further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase 1/2 trial of an immune-modulatory vaccine against IDO/PD-L1 in combination with nivolumab in metastatic melanoma. Kjeldsen, JW., Lorentzen, CL., Martinenaite, E., et al.[2023]

The study developed a framework using real-world data from the FDA's Adverse Event Reporting System to detect and filter immune-related adverse events (irAEs) associated with six FDA-approved immune checkpoint inhibitors, identifying 94 positive signals.

Out of these signals, 31 (33%) were classified as potentially new irAEs, highlighting the framework's effectiveness in discovering novel safety concerns that may not be documented in existing drug labels or literature.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Detecting and Filtering Immune-Related Adverse Events Signal Based on Text Mining and Observational Health Data Sciences and Informatics Common Data Model: Framework Development Study. Yu, Y., Ruddy, K., Mansfield, A., et al.[2020]

Cancer immunotherapies, particularly anti-CTLA4 and anti-PD1/PD-L1, are becoming more common in treatment regimens, leading to increased exposure of patients to immune-related adverse events (irAEs).

These immunotherapies can activate the immune system to fight tumors effectively, but they also have a unique toxicity profile that can cause autoimmune reactions, necessitating changes in clinical management practices to address these side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Management of adverse events associated with cancer immunotherapy]. Laparra, A., Champiat, S., Michot, JM., et al.[2021]

Immune checkpoint inhibitors (ICIs) can lead to immune-related adverse events (irAEs) due to their mechanism of action, necessitating a multidisciplinary approach for effective patient management, as highlighted by 30 real-world pharmacovigilance studies.

These studies have provided valuable insights into the patterns, kinetics, and fatality rates of various irAEs, emphasizing the need for oncologists to understand both the strengths and limitations of this data for better patient care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lessons to be Learnt from Real-World Studies on Immune-Related Adverse Events with Checkpoint Inhibitors: A Clinical Perspective from Pharmacovigilance. Raschi, E., Gatti, M., Gelsomino, F., et al.[2021]

Immunotherapy, particularly with checkpoint inhibitors like anti-PD1 and anti-CTLA-4 agents, has shown high response rates in cancer treatment, but it can lead to a variety of immune-related adverse events that are not selective.

Real-world data suggests that the characteristics and management of these adverse events may differ from clinical trial recommendations, highlighting the need for tailored approaches in using corticosteroids and other treatments for severe cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Toxicities from immunotherapy: From clinical trials to real-world clinical practice. Riveiro-Barciela, M., Trallero-Araguás, E., Martínez-Valle, F.[2021]

References

1. England pubmed.ncbi.nlm.nih.gov

Long-term follow-up of anti-PD-1 naïve patients with metastatic melanoma treated with IDO/PD-L1 targeting peptide vaccine and nivolumab. [2023]

2. United States pubmed.ncbi.nlm.nih.gov

Diversification of Antitumour Immunity in a Patient with Metastatic Melanoma Treated with Ipilimumab and an IDO-Silenced Dendritic Cell Vaccine. [2020]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Idiotypes as immunogens: facing the challenge of inducing strong therapeutic immune responses against the variable region of immunoglobulins. [2021]

4. United States pubmed.ncbi.nlm.nih.gov

A phase 1/2 trial of an immune-modulatory vaccine against IDO/PD-L1 in combination with nivolumab in metastatic melanoma. [2023]

5. England pubmed.ncbi.nlm.nih.gov

A comprehensive analysis of IDO1 expression with tumour-infiltrating immune cells and mutation burden in gynaecologic and breast cancers. [2021]

6. France pubmed.ncbi.nlm.nih.gov

[Management of immune-related toxicities associated with immune checkpoints inhibitors: Data from the multidisciplinary meeting « ToxImmun » in Eastern Occitania]. [2022]

7. Canada pubmed.ncbi.nlm.nih.gov

Detecting and Filtering Immune-Related Adverse Events Signal Based on Text Mining and Observational Health Data Sciences and Informatics Common Data Model: Framework Development Study. [2020]

8. France pubmed.ncbi.nlm.nih.gov

[Management of adverse events associated with cancer immunotherapy]. [2021]

9. France pubmed.ncbi.nlm.nih.gov

Lessons to be Learnt from Real-World Studies on Immune-Related Adverse Events with Checkpoint Inhibitors: A Clinical Perspective from Pharmacovigilance. [2021]

10. Spain pubmed.ncbi.nlm.nih.gov

Toxicities from immunotherapy: From clinical trials to real-world clinical practice. [2021]

11. England pubmed.ncbi.nlm.nih.gov

The paradoxical patterns of expression of indoleamine 2,3-dioxygenase in colon cancer. [2021]

12. England pubmed.ncbi.nlm.nih.gov

Indoleamine 2,3-dioxygenase, tumor-induced tolerance and counter-regulation. [2022]

13. England pubmed.ncbi.nlm.nih.gov

Targeting indoleamine-2,3-dioxygenase in cancer: Scientific rationale and clinical evidence. [2020]