VIO-01 for Recurrent Cancer

No longer recruiting at 2 trial locations

Overseen By Lisa Fitzgerald

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Valerio Therapeutics

Disqualifiers: Neurologic disorders, HER2 positive, others

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

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new drug, VIO-01 (also known as OX425), for individuals with solid tumor cancers to assess its safety and efficacy. The first part of the trial determines the safest dose when the drug is used alone or with other cancer treatments. The second part examines its effects on advanced cancers, such as ovarian cancer, with specific genetic features. Suitable candidates have advanced solid tumors, particularly those with specific genetic changes, and have not found success with other treatments. Participants will adhere to a schedule for site visits to undergo health checks and receive the drug. As a Phase 1 trial, participants will be among the first to receive this new treatment, aiding researchers in understanding its effects in humans.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on endocrine therapy for hormone receptor-positive breast cancer, it must be completed at least 7 days before starting the trial treatment.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on endocrine therapy for hormone receptor-positive breast cancer, it must be completed at least 7 days before starting the trial treatment.

Is there any evidence suggesting that VIO-01 is likely to be safe for humans?

Research shows that VIO-01 is undergoing safety testing for treating various solid tumor cancers. Early studies examine its safety when administered alone or with other cancer treatments, as well as patient tolerance.

Since this trial is in its early stages, researchers continue to collect safety data in humans. They aim to find the optimal dose that minimizes side effects. However, early preclinical research demonstrated that VIO-01 is highly effective against tumors. This finding is promising, suggesting the treatment could be effective against tumors.

For those considering trial participation, it's important to know that the primary goal at this stage is to ensure the treatment is safe and well-tolerated. This trial will help determine if VIO-01 can be safely used in people with solid tumors. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about VIO-01 for recurrent cancer because it offers a novel approach compared to existing treatments. Unlike traditional chemotherapy, which targets rapidly dividing cells broadly, VIO-01 is specifically designed to work on tumors with HRRm or HRD+ mutations. This targeted approach could potentially lead to more effective treatment outcomes with fewer side effects. Additionally, VIO-01 is administered via a weekly intravenous infusion, which might provide a more consistent delivery of the drug compared to some oral medications that require daily dosing.

What evidence suggests that VIO-01 might be an effective treatment for recurrent cancer?

Research shows that VIO-01, which participants in this trial may receive, could be a promising treatment for certain cancers. Studies have found that it can trick cancer cells into not repairing themselves, enhancing its ability to fight tumors. This treatment has proven effective in various solid tumor cancers. It shows particular promise for treating ovarian cancer, even in cases without the usual genetic mutations. These early findings suggest that VIO-01 might work well when combined with other cancer treatments. ^{2 4 5 6 7}

Who Is on the Research Team?

Alexander Philipovskiy

Principal Investigator

Florida Cancer Specialists & Research Institute

Are You a Good Fit for This Trial?

This trial is for people with recurrent solid tumors, including specific types like prostate, ovarian, and breast cancers. Participants should have previously tried standard treatments without success. The study will also focus on individuals with advanced HRRm or HRD+ solid tumors and those with the same conditions in recurrent ovarian cancer.

Inclusion Criteria

Participants must have measurable disease per RECIST 1.1

My cancer has worsened despite treatment, or I can't tolerate standard treatments.

My breast cancer has returned or spread, and I know my cancer's hormone and HER2 status.

Exclusion Criteria

I have had more than one treatment for my cancer after it spread.

I have a chronic neurological condition like MS or Parkinson's.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Multiple dose levels of VIO-01 will be administered via intravenous infusion over a 60-minute period once weekly to determine the highest dose without unacceptable side effects

12 months

Weekly visits for infusion

Dose Expansion

Participants with advanced HRRm or HRD+ solid tumors or ovarian cancer will receive the recommended Phase 2 dose of VIO-01 via intravenous infusion over a 60-minute period once weekly

12 months

Weekly visits for infusion

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• VIO-01

Trial Overview The trial is testing VIO-01's safety when used alone or alongside other anti-cancer therapies. It consists of two parts: determining the maximum safe dose and how well patients tolerate it (Part 1), followed by assessing its effectiveness in advanced HRRm/HRD+ solid tumors (Part 2).

How Is the Trial Designed?

Group I: Dose Expansion HRRm or HRD+ Solid Tumors Experimental Treatment 1 Intervention

Participants with advanced HRRm or HRD+ solid tumors will be administered recommended Phase 2 dose of VIO-01 via intravenous infusion over a 60-minute period once weekly.

Group II: Dose Expansion HRRm or HRD+ Ovarian Cancer Experimental Treatment 1 Intervention

Participants with advanced HRRm or HRD+ ovarian cancer will be administered recommended Phase 2 dose of VIO-01via intravenous infusion over a 60-minute period once weekly.

Group III: Dose Escalation Experimental Treatment 1 Intervention

Dose escalation: Multiple dose levels of VIO-01 will be administered via intravenous infusion over a 60-minute period once weekly.

Who Is Running the Clinical Trial?

Valerio Therapeutics

Lead Sponsor

Trials

29

Recruited

3,800+

Published Research Related to This Trial

The oncolytic adenovirus expressing variant interleukin-2 (vIL-2), known as TILT-452, significantly enhances the cancer-killing ability of natural killer (NK) cells in ovarian cancer, as demonstrated in both ex vivo co-culture experiments and in vivo studies using patient-derived xenografts in mice.

Mechanistically, the vIL-2 virus increases the levels of granzyme B in NK and CD8+ T cells, which are crucial for attacking cancer cells, while maintaining stable levels of regulatory T cells, suggesting a targeted enhancement of the immune response against ovarian cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Boosting cytotoxicity of adoptive allogeneic NK cell therapy with an oncolytic adenovirus encoding a human vIL-2 cytokine for the treatment of human ovarian cancer. Quixabeira, DCA., Pakola, S., Jirovec, E., et al.[2023]

Oncolytic viruses (OVs), like talimogene laherparepvec (T-VEC), are a promising cancer treatment that selectively target tumor cells, induce immune responses, and have a favorable safety profile compared to traditional therapies.

T-VEC is currently the only widely approved OV for treating recurrent melanoma, and while there is growing clinical data supporting its use, further research is needed to fully understand the biology and optimize the application of OVs in cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapy with oncolytic viruses: progress and challenges. Shalhout, SZ., Miller, DM., Emerick, KS., et al.[2023]

Oncolytic viruses, like reovirus, show promise as a new cancer treatment with a low toxicity profile and the ability to specifically target and kill tumor cells through mechanisms like apoptosis.

Reovirus has demonstrated efficacy in pre-clinical studies and early-phase clinical trials, especially when combined with traditional therapies like chemotherapy and radiation, making it a potential game-changer in overcoming resistance to current cancer treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oncolytic viral therapy using reovirus. Thirukkumaran, C., Morris, DG.[2009]

RNA oncolytic viruses (OVs) are promising cancer therapies that can specifically target and destroy tumor cells while leaving normal cells unharmed, but challenges like poor tumor penetration and resistance still exist.

Combining OVs with cytotoxic agents or using stealth delivery methods may enhance their effectiveness by improving virus delivery and replication within tumors, paving the way for better clinical outcomes in cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The emergence of combinatorial strategies in the development of RNA oncolytic virus therapies. Nguyen, TL., Tumilasci, VF., Singhroy, D., et al.[2009]

Oncolytic viruses (OVs), such as the Maraba virus, can effectively reduce metastatic cancer burden and enhance immune responses when administered before surgical tumor removal, as shown in aggressive murine models of triple-negative breast cancer.

Various OVs, including Vesicular stomatitis virus and Herpes simplex virus, demonstrated the ability to improve survival outcomes and provide long-term protection against cancer recurrence, highlighting the potential of OV therapy in the pre-operative treatment setting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pre-surgical neoadjuvant oncolytic virotherapy confers protection against rechallenge in a murine model of breast cancer. Martin, NT., Roy, DG., Workenhe, ST., et al.[2020]

Oncolytic viruses (OVs) can selectively target and destroy cancer cells while also acting as a vaccine by releasing tumor-specific antigens, which helps stimulate the immune system against the tumor.

Recent studies indicate that combining OVs with immune checkpoint inhibitors may enhance their effectiveness, suggesting a promising strategy to improve cancer treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combination Immunotherapy Using Oncolytic Virus for the Treatment of Advanced Solid Tumors. Oh, CM., Chon, HJ., Kim, C.[2021]

Oncolytic viruses, like talimogene laherparepvec (T-vec), have gained FDA approval and show promise as cancer therapies, but their effectiveness against solid tumors remains limited despite extensive research.

Recent advancements in viral retargeting, genetic editing, and combination therapies may enhance the efficacy of oncolytic virotherapy, indicating a need for optimization to improve clinical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oncolytic Viruses for Cancer Therapy: Barriers and Recent Advances. Zheng, M., Huang, J., Tong, A., et al.[2020]

Oncolytic viruses (OVs) are effective cancer treatments that selectively target and kill tumor cells while also stimulating the immune system to enhance antitumor immunity, making them a promising option for cancer therapy.

Genetic engineering of OVs and their combination with other immunotherapies, such as HDAC inhibitors and cyclophosphamide, can significantly improve their efficacy by promoting immune responses and overcoming the immunosuppressive tumor microenvironment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oncolytic viruses as therapeutic cancer vaccines. Bartlett, DL., Liu, Z., Sathaiah, M., et al.[2021]

Oncolytic viruses (OVs) can selectively replicate in cancer cells, leading to tumor destruction through direct cell lysis and immune responses, showcasing their potential as a cancer treatment.

Recent advancements in understanding OVs have led to the FDA approving the first oncolytic virus for cancer therapy, highlighting their growing role in combination with standard cancer treatments and ongoing clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

From Benchtop to Bedside: A Review of Oncolytic Virotherapy. Choi, AH., O'Leary, MP., Fong, Y., et al.[2020]

The oncolytic adenovirus Ad5/3-E2F-d24-vIL2 (vIL-2 virus) significantly enhances the effectiveness of tumor-infiltrating lymphocytes (TILs) in killing ovarian cancer cells, as shown in both ex vivo and in vivo studies involving patient-derived xenograft models.

Combining vIL-2 virus with TIL therapy not only improved cancer cell killing but also induced a more cytotoxic immune response, evidenced by increased granzyme B levels in various immune cells, suggesting a promising immunotherapeutic strategy for advanced ovarian cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Improving the cytotoxic response of tumor-infiltrating lymphocytes towards advanced stage ovarian cancer with an oncolytic adenovirus expressing a human vIL-2 cytokine. Quixabeira, DCA., Jirovec, E., Pakola, S., et al.[2023]

C134, a next-generation oncolytic virus, shows improved safety and efficacy in treating malignant gliomas by inducing early interferon signaling that limits replication in non-cancerous cells while effectively targeting tumor cells.

The study demonstrated that C134 elicits a strong T cell-mediated anti-tumor response, leading to improved survival in animal models, and that repeated administration enhances its anti-tumor effects and creates lasting immune memory against the tumor.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chimeric HCMV/HSV-1 and Δγ134.5 oncolytic herpes simplex virus elicit immune mediated antigliomal effect and antitumor memory. Ghonime, MG., Jackson, J., Shah, A., et al.[2021]

Oncolytic viruses (OVs) are being tested in clinical trials for cancer treatment, with adenovirus being the most commonly used, and most trials focusing on melanoma and gastrointestinal cancers, showing low-grade adverse events.

Out of 3233 patients studied, only 9% had objective responses to OV treatment, but 21.1% achieved disease control, indicating that while OVs show promise, more research is needed to fully understand their efficacy and immune response mechanisms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical landscape of oncolytic virus research in 2020. Macedo, N., Miller, DM., Haq, R., et al.[2021]

Oncolytic viruses (OVs) are emerging as a promising treatment for cancer patients who do not respond well to traditional immune checkpoint inhibitors, as they can selectively replicate in tumor cells and enhance immune responses.

OVs not only kill tumor cells and release antigens that stimulate the immune system, but they also have a strong safety profile, making them suitable for combination therapies with other cancer treatments to improve outcomes for patients with limited options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Optimizing oncolytic virotherapy in cancer treatment. Harrington, K., Freeman, DJ., Kelly, B., et al.[2020]

Citations

1. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2024-05250

A Phase 1/2 Study of VIO-01 in Participants With Recurrent ... Part 2 of the trial will further test VIO-01's effect in participants with advanced HRRm or HRD+ solid tumors and HRRm/HRD+ recurrent ovarian cancer.

2. delta.larvol.com delta.larvol.com/Products/?ProductId=f7c30911-cfea-41e0-be20-3e1ab0a2c9fb

VIO-01 / Valerio Therap A Phase 1/2 Study of VIO-01 in Participants With Recurrent Solid Tumors ... VIO-01 in HRD+ ovarian cancer and in HRRm/HRD+ solid tumors. The Phase 2 ...

3. valeriotx.com valeriotx.com/valerio-therapeutics-provides-clinical-development-update-on-its-phase-1-2-vio-01-clinical-trial/

Valerio Therapeutics Provides Clinical Development ... The pan trapping nature of VIO-01 allows for treatment of a wide range of potential solid tumor indications rather than restrictions to BRCA1/2 ...

4. valeriotx.com valeriotx.com/wp-content/uploads/2023/11/2023-07-17-valeriotx-gemstone-iii-bgco-corporate.pdf

Developing Novel DNA Decoy Therapeutics For Precision ... VIO-01 Anti-Tumor Activity In Ovarian Cancer Is Independent Of. Genetic ... Recurrent ovarian, breast, prostate cancer. (combination with PARPi). Phase I.

5. valeriotx.com valeriotx.com/valerio-therapeutics-reports-its-half-year-2024-financial-results-and-provides-an-update-on-its-activities/

Valerio Therapeutics Reports its Half-Year 2024 Financial ... Valerio Therapeutics presented new preclinical data confirming the pan-DDR DNA decoy effect of VIO-01 and the high anti-tumor activity in tumor ...

6. ctv.veeva.com ctv.veeva.com/study/a-phase-1-2-study-of-vio-01-in-participants-with-recurrent-solid-tumors

A Phase 1/2 Study of VIO-01 in Participants With Recurrent ... The goal of this phase 1/2 clinical trial is to investigate the safety of an investigational drug called VIO-01 when taken by people who ...

7. trial.medpath.com trial.medpath.com/organization/b55345c3a9dd3c16/valerio-therapeutics

VALERIO THERAPEUTICS | MedPath ... VIO-01 in Participants With Recurrent Solid Tumors. Phase 1. Terminated. Conditions. Breast Cancer. Prostate Cancer. Advanced or Metastatic ...