SVV-001 + Nivolumab + Ipilimumab for Neuroendocrine Cancer

Overseen By Nailet Real Bestard, MS

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Aman Chauhan, MD

Must not be taking: Immunosuppressants, Steroids, others

Disqualifiers: Active malignancy, Autoimmune disease, Infection, others

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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 12 months

36 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment combination for neuroendocrine cancer, including the drugs Seneca Valley Virus-001 (SVV-001, an experimental treatment), Nivolumab, and Ipilimumab. The goal is to determine the highest dose and frequency of these drugs that patients can tolerate and that perform as well as or better than current treatments. It targets individuals with advanced neuroendocrine tumors unresponsive to at least one treatment. Participants will be divided into groups to try different doses and schedules of the new treatment. This trial may be suitable for those with progressing neuroendocrine tumors despite previous treatments. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new experimental therapy.

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 systemic steroids or other immunosuppressive medications, you may need to adjust your treatment as these could affect your eligibility.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that Seneca Valley Virus-001 (SVV-001) is a new virus designed to target cancer cells. In lab studies, it worked well with drugs like nivolumab and ipilimumab, which are already used to treat some cancers. These studies found that the combination could shrink tumors and help the body’s immune system fight cancer more effectively.

However, specific safety information for SVV-001 when used with nivolumab and ipilimumab in humans is not yet available. This trial is in its early stages, with the main goal of determining the treatment's safety and tolerability. In early trials like this, researchers are still figuring out the best dose and frequency that can be given without causing too many side effects.

While nivolumab and ipilimumab are generally well-tolerated on their own, the combination with SVV-001 is still under study. Participants should know that the trial primarily focuses on testing safety and tolerability, rather than effectiveness. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Seneca Valley Virus-001 (SVV-001), Nivolumab, and Ipilimumab for neuroendocrine cancer because it offers a novel approach compared to standard treatment options like chemotherapy and targeted therapies. Unlike traditional methods, SVV-001 is an oncolytic virus that specifically targets and infects cancer cells, potentially sparing healthy cells. Meanwhile, Nivolumab and Ipilimumab are immune checkpoint inhibitors that boost the body's own immune response against cancer. This combination could lead to more effective and targeted cancer destruction, offering hope for better outcomes in a condition that is often challenging to treat.

What evidence suggests that this trial's treatments could be effective for neuroendocrine cancer?

This trial will evaluate different dosing regimens of SVV-001 combined with Nivolumab and Ipilimumab for treating neuroendocrine tumors. Studies have shown promising results for this combination, with early research indicating that it eliminated tumors and enhanced the body's ability to fight cancer. These findings suggest that this treatment might shrink or control neuroendocrine tumors. Additionally, early trials indicated that using SVV-001 with Nivolumab and Ipilimumab could be safe and manageable for patients. While more research is needed, the early data is encouraging for those considering this treatment. ^{1 4 6 7 8}

Who Is on the Research Team?

Aman Chauhan, MD

Principal Investigator

University of Miami

Are You a Good Fit for This Trial?

This trial is for patients with specific types of neuroendocrine tumors: poorly differentiated carcinomas or high-grade, well-differentiated tumors. Details on who can join are not fully provided, but typically include factors like age, health status, and previous treatments.

Inclusion Criteria

Life expectancy of 6 months or greater as assessed by the treating oncologist

I have recovered from side effects of previous treatments, except for hair loss.

My cancer is a specific type of aggressive neuroendocrine tumor.

Exclusion Criteria

I haven't had chemotherapy, radiation, or biologic therapy recently.

I have a condition that increases my risk of bleeding from biopsies.

I have a primary immune deficiency or have been taking high-dose steroids or other immune-suppressing drugs recently.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive SVV-001 in combination with Nivolumab and Ipilimumab therapy. The treatment phase aims to determine the maximum tolerated dose and frequency.

Up to 12 months

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of progression-free survival and overall response rate.

Up to 12 months

Extension

Participants may continue to be monitored for duration of response and clinical benefit rate.

Up to 2 years

What Are the Treatments Tested in This Trial?

Interventions

• Ipilimumab
• Nivolumab
• Seneca Valley Virus-001 (SVV-001)

Trial Overview The study tests the Seneca Valley Virus-001 (SVV-001) combined with Nivolumab and Ipilimumab to find the highest safe dose and frequency against neuroendocrine tumors. It aims to match or exceed current treatment effectiveness.

How Is the Trial Designed?

Group I: SVV-001 Single Dose Treatment Group Experimental Treatment 3 Interventions

Participants in this group will receive a single dose of SVV-001 on Day 1, in combination with Nivolumab and Ipilimumab therapy. Total participation duration is up to 2 years.

Group II: SVV-001 RP2D Treatment Group Experimental Treatment 3 Interventions

Participants is this group will receive the recommended phase 2 dose and frequency of SVV-001 in combination with Nivolumab and Ipilimumab therapy. Total participation duration is up to 2 years.

Group III: SVV-001 Multi-Dose Treatment Group Experimental Treatment 3 Interventions

Participants in this group will receive multiple doses of SVV-001, beginning on Day 1, in combination with Nivolumab and Ipilimumab therapy. Total participation duration is up to 2 years.

Who Is Running the Clinical Trial?

Aman Chauhan, MD

Lead Sponsor

Trials

1

Recruited

40+

Seneca Therapeutics

Collaborator

Trials

1

Recruited

40+

Published Research Related to This Trial

Ipilimumab is a well-tolerated immunotherapy that significantly improves survival in patients with malignant melanoma by blocking CTLA-4, which enhances the immune response against tumors.

Therapeutic responses to ipilimumab can take time to manifest, often peaking between 12 and 24 weeks, and the management of immune-related side effects is crucial, as they can occur in 10%-15% of patients but do not hinder the drug's antitumor efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ipilimumab: unleashing the power of the immune system through CTLA-4 blockade. Boasberg, P., Hamid, O., O'Day, S.[2021]

In the KEYNOTE-028 study, pembrolizumab showed antitumor activity in patients with well-differentiated or moderately-differentiated neuroendocrine tumors (NETs), with objective response rates of 12% for carcinoid tumors and 6.3% for pancreatic NETs after a median follow-up of 20 to 21 months.

The treatment was generally well-tolerated, with 68% to 69% of patients experiencing treatment-related adverse events, the most common being diarrhea and fatigue, indicating that while effective, monitoring for side effects is important.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of programmed death-ligand 1-positive advanced carcinoid or pancreatic neuroendocrine tumors: Results from the KEYNOTE-028 study. Mehnert, JM., Bergsland, E., O'Neil, BH., et al.[2021]

Ipilimumab is a monoclonal antibody that blocks CTLA-4, enhancing T-cell activation and leading to significant antitumor immune responses, which has been shown to improve survival in patients with advanced melanoma in two global phase 3 clinical studies involving over 13,000 patients.

Approved in over 40 countries, including the U.S. and EU, ipilimumab is the first treatment to demonstrate an overall survival benefit for advanced melanoma, with ongoing trials exploring its efficacy in other cancers like lung and gastric cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Ipilimumab]. Tokudome, T.[2017]

In a study of 51 patients with metastatic melanoma treated with immune checkpoint inhibitors, 11.7% developed hypophysitis, highlighting a notable incidence of this immune-mediated adverse event.

Patients who experienced immune-mediated adverse events (IMAEs) showed significantly improved overall survival and progression-free survival compared to those who did not, suggesting a potential link between IMAEs and better treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hypophysitis induced by immune checkpoint inhibitors in a Scottish melanoma population. Wei, KZ., Baxter, M., Casasola, R.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06889493

NCT06889493 | SVV-001 With Nivolumab and Ipilimumab ... The purpose of this study is to determine: The highest dose of the trial intervention that targets neuroendocrine tumors and is tolerated by patients.

2. curetoday.com curetoday.com/view/trial-of-svv-001-opdivo-and-yervoy-in-neuroendocrine-tumors-launching

Trial of SVV-001, Opdivo and Yervoy in Neuroendocrine ... The trial evaluates Opdivo, Yervoy, and Seneca Valley Virus-001 for tolerability and efficacy compared to standard treatments.

3. firstwordpharma.com firstwordpharma.com/story/5966672

Seneca Therapeutics Announces the Dosing of the First ... In preclinical studies, SVV-001 administered in conjunction with nivolumab and ipilimumab eradicated the tumors, induced a systemic anti-tumor ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5317273/

Phase I Clinical Study of Seneca Valley Virus (SVV-001), a ... We conducted a first-in-human, first-in-class phase I clinical trial of this agent in patients with cancers with neuroendocrine features, including small cell ...

5. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2025-02478

An Oncolytic Virus (SVV-001) in Combination with ... Giving SVV-001 in combination with nivolumab and ipilimumab may be safe, tolerable and/or effective in treating patients with neuroendocrine cancers or high- ...

6. withpower.com withpower.com/trial/phase-1-carcinoma-neuroendocrine-4-2025-ecb0a

SVV-001 + Nivolumab + Ipilimumab for Neuroendocrine ... There is no specific safety data available for Seneca Valley Virus-001 (SVV-001) in this context. Show more. What makes the drug combination of SVV ...

7. jitc.bmj.com jitc.bmj.com/content/13/Suppl_2/A678

597 A phase 1 trial of the oncolytic virus SVV-001 in ... Seneca Valley Virus (SVV-001) is a novel oncolytic RNA virus that has shown synergistic activity with ICIs in preclinical models. Additionally, ...

8. news.med.miami.edu news.med.miami.edu/clinical-trial-opens-for-patients-with-high-grade-neuroendocrine-cancer/

Clinical Trial Opens for Patients with High-Grade ... - InventUM In the new trial, Dr. Chauhan will combine immunotherapy drugs called checkpoint inhibitors with SVV-001 (Seneca Valley Virus-001), an oncolytic ...