VIO-01 for Recurrent Cancer

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

6 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a new drug called VIO-01 to see if it can help treat certain types of advanced cancers with specific genetic mutations. The study will check how safe the drug is, how well the body absorbs it, and its effects on the tumors.

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.

What data supports the effectiveness of the treatment VIO-01, OX425 for recurrent cancer?

Oncolytic viruses (OVs), like those potentially related to VIO-01, have shown promise in cancer treatment by selectively targeting and killing cancer cells while also boosting the body's immune response against tumors. Studies have demonstrated that OVs can improve outcomes in various cancer models, suggesting potential effectiveness for recurrent cancer. ^{1 2 3 4 5}

What data supports the effectiveness of the treatment VIO-01, OX425 for recurrent cancer?

Research on oncolytic viruses (OVs), which are similar to VIO-01, shows they can selectively target and kill cancer cells while also boosting the body's immune response against tumors. Studies have demonstrated that OVs can improve survival and reduce tumor growth in various cancer models, suggesting potential effectiveness for recurrent cancer. ^{1 2 3 4 5}

Is VIO-01 (also known as OX425) safe for humans?

Oncolytic viruses, like the one used in VIO-01, generally have a tolerable safety profile with minimal human toxicity, as they selectively target and replicate in cancer cells. ^{6 7 8 9 10}

Is VIO-01 (also known as OX425) safe for humans?

Oncolytic viruses, like the one used in VIO-01, generally have a tolerable safety profile with minimal human toxicity, as they selectively target and replicate in cancer cells. ^{6 7 8 9 10}

How is the treatment VIO-01 (OX425) different from other treatments for recurrent cancer?

VIO-01 (OX425) is unique because it is an oncolytic virus therapy, which means it uses viruses to specifically target and destroy cancer cells while also stimulating the body's immune system to fight the cancer. This approach is different from traditional treatments like chemotherapy, as it acts like a vaccine by releasing tumor-specific antigens and can be combined with other therapies to enhance its effectiveness. ^{3 5 11 12 13}

How is the treatment VIO-01 different from other treatments for recurrent cancer?

VIO-01 is unique because it uses oncolytic viruses, which are viruses that specifically target and destroy cancer cells while sparing normal cells. This approach not only directly kills cancer cells but also stimulates the body's immune system to attack the tumor, potentially offering long-lasting protection against cancer recurrence. ^{3 5 11 12 13}

Research Team

Alexander Philipovskiy

Principal Investigator

Florida Cancer Specialists & Research Institute

Eligibility Criteria

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

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

Treatment Details

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).

Participant Groups

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+

Findings from Research

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]

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 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 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), 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]

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]

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]

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]

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]

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]

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) 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]

References

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

Optimizing oncolytic virotherapy in cancer treatment. [2020]

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

Oncolytic Viruses for Cancer Therapy: Barriers and Recent Advances. [2020]

3. England pubmed.ncbi.nlm.nih.gov

Clinical landscape of oncolytic virus research in 2020. [2021]

4. England pubmed.ncbi.nlm.nih.gov

Oncolytic viruses as therapeutic cancer vaccines. [2021]

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

Pre-surgical neoadjuvant oncolytic virotherapy confers protection against rechallenge in a murine model of breast cancer. [2020]

6. England 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. [2023]

7. England pubmed.ncbi.nlm.nih.gov

Therapy with oncolytic viruses: progress and challenges. [2023]

8. England 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. [2023]

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

Oncolytic viral therapy using reovirus. [2009]

10. Switzerland pubmed.ncbi.nlm.nih.gov

From Benchtop to Bedside: A Review of Oncolytic Virotherapy. [2020]

11. India pubmed.ncbi.nlm.nih.gov

The emergence of combinatorial strategies in the development of RNA oncolytic virus therapies. [2009]

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

Chimeric HCMV/HSV-1 and Δγ134.5 oncolytic herpes simplex virus elicit immune mediated antigliomal effect and antitumor memory. [2021]

13. Switzerland pubmed.ncbi.nlm.nih.gov

Combination Immunotherapy Using Oncolytic Virus for the Treatment of Advanced Solid Tumors. [2021]