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

Trial Summary

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.

What data supports the effectiveness of the drug combination of SVV-001, Nivolumab, and Ipilimumab for neuroendocrine cancer?

Research shows that the combination of ipilimumab and nivolumab, which are part of the treatment, has shown promising results in patients with high-grade neuroendocrine neoplasms, with response rates ranging from 9% to 44%. ^{1 2 3 4 5}

What safety information is available for the combination of SVV-001, Nivolumab, and Ipilimumab in humans?

Nivolumab and Ipilimumab, both used in cancer treatment, can cause immune-related side effects like inflammation of the pituitary gland (hypophysitis), skin rash, and inflammation of the colon (colitis). These side effects are generally manageable with proper monitoring and treatment. There is no specific safety data available for Seneca Valley Virus-001 (SVV-001) in this context. ^{6 7 8 9 10}

What makes the drug combination of SVV-001, Nivolumab, and Ipilimumab unique for neuroendocrine cancer?

This drug combination is unique because it combines a virus-based therapy (SVV-001) with two immunotherapy drugs (Nivolumab and Ipilimumab) that help the immune system attack cancer cells. This approach is novel for neuroendocrine cancer, which has limited treatment options and often lacks standard guidelines for recurrent cases. ^{1 2 11 12 13}

What is the purpose of this trial?

The purpose of this study is to determine: 1. The highest dose of the trial intervention that targets neuroendocrine tumors and is tolerated by patients. 2. The highest frequency of dosing of the trial intervention that targets neuroendocrine tumors and is tolerated by patients. 3. The highest dose and frequency of dosing of the trial intervention that targets neuroendocrine tumors with at least the same degree of effectiveness and tolerability as currently available (standard of care) treatments for patients with neuroendocrine tumors.

Research Team

Aman Chauhan, MD

Principal Investigator

University of Miami

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

References

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

Immunotherapy of Ipilimumab and Nivolumab in Patients with Advanced Neuroendocrine Tumors: A Subgroup Analysis of the CA209-538 Clinical Trial for Rare Cancers. [2021]

2. England pubmed.ncbi.nlm.nih.gov

The prognostic impact of the immune microenvironment in small-cell neuroendocrine carcinoma of the uterine cervix: PD-L1 and immune cell subtypes. [2022]

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

Programmed Cell Death Ligand Expression Drives Immune Tolerogenesis across the Diverse Subtypes of Neuroendocrine Tumours. [2021]

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

Efficacy of ipilimumab and nivolumab in patients with high-grade neuroendocrine neoplasms. [2022]

5. United States 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. [2021]

6. England pubmed.ncbi.nlm.nih.gov

Nivolumab-induced autoimmune diabetes mellitus presenting as diabetic ketoacidosis in a patient with metastatic mucosal melanoma. [2023]

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

Hypophysitis induced by immune checkpoint inhibitors in a Scottish melanoma population. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Immune check point inhibitors-induced hypophysitis: a retrospective analysis of the French Pharmacovigilance database. [2021]

9. Japan pubmed.ncbi.nlm.nih.gov

[Ipilimumab]. [2017]

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

Ipilimumab: unleashing the power of the immune system through CTLA-4 blockade. [2021]

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

Is There a Place for Temozolomide plus Nivolumab among Neuroendocrine Neoplasms? [2023]

12. Switzerland pubmed.ncbi.nlm.nih.gov

PD-L1 Expression and Immune Cell Infiltration in Gastroenteropancreatic (GEP) and Non-GEP Neuroendocrine Neoplasms With High Proliferative Activity. [2020]

13. Netherlands pubmed.ncbi.nlm.nih.gov

Ipilimumab and nivolumab for recurrent neuroendocrine cervical carcinoma. [2022]