NeoVax + Ipilimumab for Kidney Cancer

Overseen By Toni Choueiri, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Patrick Ott, MD

Must not be taking: Immune-modulatory agents

Disqualifiers: Active brain metastases, Autoimmune diseases, Chronic infections, 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: 7

19 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot be on certain immune-modulatory agents or other investigational cancer therapies, and you should not be using corticosteroids above a certain dose. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the treatment NeoVax + Ipilimumab for kidney cancer?

Research suggests that personalized mRNA vaccines, like NeoVax, show clinical benefits in solid tumors by targeting specific tumor antigens, and immune checkpoint inhibitors like Ipilimumab have been effective in enhancing immune responses in cancer therapy. Additionally, studies indicate that certain immune subtypes of kidney cancer may respond better to these personalized vaccine approaches. ^{1 2 3 4 5}

Is the combination of NeoVax and Ipilimumab safe for humans?

Ipilimumab, when used with other treatments like nivolumab for kidney cancer, can cause immune-related side effects, which are reactions where the immune system attacks normal organs and tissues. These side effects can vary in severity, but they are a known risk when using this type of treatment. ^{6 7 8 9 10}

What makes the NeoVax + Ipilimumab treatment unique for kidney cancer?

The NeoVax + Ipilimumab treatment is unique because it combines a personalized cancer vaccine with an immune checkpoint inhibitor, potentially offering a tailored approach to stimulate the immune system specifically against kidney cancer, unlike standard treatments that do not include personalized vaccines. ^{11 12 13 14 15}

What is the purpose of this trial?

This research study is evaluating a new type of Kidney Cancer vaccine called "Personalized NeoAntigen Cancer Vaccine"as a possible treatment for Kidney Cancer. The following intervention will be involved in this study: * Personalized Neoantigen Vaccine * Poly-ICLC (Hiltonol) * Ipilimumab

Research Team

Patrick Ott, MD, PhD

Principal Investigator

Dana-Farber Cancer Institute

Toni Choueiri, MD

Principal Investigator

Dana-Farber Cancer Institute

Eligibility Criteria

This trial is for adults over 18 with stage III or IV clear cell renal cell carcinoma (ccRCC) that can be surgically removed. Participants must understand and sign a consent form, agree to provide tissue samples, have an ECOG performance status ≤1, and meet certain blood test criteria.

Inclusion Criteria

absolute neutrophil count ≥1,500/mcL

I am suspected to have advanced kidney cancer that can be entirely removed by surgery.

Ability to understand and the willingness to sign a written informed consent document.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Surgery

Patients will undergo surgery with the intent to resect the primary kidney tumor

1 week

Priming Treatment

Priming doses of NeoVax will be administered on days 1, 4, 8, 15, and 22

3 weeks

5 visits (in-person)

Boost Phase

Vaccine will be administered on days 78 (week 12) and 134 (week 20)

8 weeks

2 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Ipilimumab
• Personalized NeoAntigen Cancer Vaccine

Trial Overview The study tests a new vaccine called 'Personalized NeoAntigen Cancer Vaccine' alongside Poly-ICLC (Hiltonol) and Ipilimumab as potential treatments for kidney cancer. The aim is to see if this combination helps in treating ccRCC after surgery.

Participant Groups

Group I: Neovax in Combination with Ipilimumab Experimental Treatment 2 Interventions

Patients will undergo surgery with the intent to resect the primary kidney tumor Neovax is a combination of Poly-ICLC and Neoantigen Peptides Priming doses of NeoVax will be administered on days 1, 4, 8, 15, and 22 * In the boost phase, vaccine will be administered on days 78 (week 12) and 134 (week 20 Ipilimumab will be injected within 1 cm of each NeoVax administration

Group II: NeoVax alone Experimental Treatment 1 Intervention

Patients will undergo surgery with the intent to resect the primary kidney tumor Neovax is a combination of Poly-ICLC and Neoantigen Peptides Priming doses of NeoVax will be administered on days 1, 4, 8, 15, and 22 * In the boost phase, vaccine will be administered on days 78 (week 12) and 134 (week 20)

Ipilimumab is already approved in United States, European Union for the following indications:

Approved in United States as Yervoy for:

• Advanced melanoma
• Stage III unresectable melanoma
• Stage IV metastatic melanoma

Approved in European Union as Yervoy for:

• Advanced melanoma
• Stage III unresectable melanoma
• Stage IV metastatic melanoma

Who Is Running the Clinical Trial?

Patrick Ott, MD

Lead Sponsor

Trials

2

Recruited

30+

Patrick Ott, MD, PhD

Lead Sponsor

Trials

2

Recruited

30+

Bristol-Myers Squibb

Industry Sponsor

Trials

2,731

Recruited

4,127,000+

Headquarters

New York City, USA

Known For

Oncology & Cardiovascular

Top Products

Eliquis, Opdivo, Revlimid, Orencia

Christopher Boerner

Bristol-Myers Squibb

Chief Executive Officer since 2023

PhD in Business Administration from the Haas School of Business, University of California, Berkeley; BA in Economics and History from Washington University in St. Louis

Deepak L. Bhatt

Bristol-Myers Squibb

Chief Medical Officer since 2024

MD from Yale University; MSc in Clinical Epidemiology from the University of Pennsylvania

Oncovir, Inc.

Industry Sponsor

Trials

25

Recruited

680+

Findings from Research

All patients with renal cell carcinoma (RCC) expressed at least one tumor-associated antigen (TAA), with 80% showing two or more, indicating a strong potential for T-cell activation in immunotherapy.

Based on HLA expression analysis, at least 30% of RCC patients are eligible for monovalent immunotherapy and 41% for polyvalent immunotherapy, supporting the rationale for future vaccination trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Simultaneous expression of T-cell activating antigens in renal cell carcinoma: implications for specific immunotherapy. Ringhoffer, M., Müller, CR., Schenk, A., et al.[2019]

In a study of 52 patients with metastatic renal cell carcinoma treated with nivolumab plus ipilimumab, the 1-year progression-free survival rate was 55% and the overall survival rate was 75%, indicating promising efficacy of this treatment combination.

The treatment was associated with a 39% objective response rate, and while 69% of patients experienced immune-related adverse events, the incidence of severe events was lower compared to previous studies, suggesting a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of first-line nivolumab plus ipilimumab in patients with metastatic renal cell carcinoma: A multicenter retrospective study. Tanaka, T., Hatakeyama, S., Numakura, K., et al.[2021]

In a study of 69 patients with metastatic renal cell carcinoma treated with nivolumab plus ipilimumab, those who experienced immune-related adverse events (irAEs) had significantly better overall survival (OS) and progression-free survival compared to those without irAEs, suggesting that irAEs may be a positive indicator of treatment response.

The study identified three key factors influencing OS: the presence of irAEs, C-reactive protein levels, and performance status, indicating that monitoring these factors could help predict patient outcomes in mRCC treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prognostic Impact of Immune-Related Adverse Events as First-Line Therapy for Metastatic Renal Cell Carcinoma Treated With Nivolumab Plus Ipilimumab: A Multicenter Retrospective Study. Nukaya, T., Takahara, K., Yoshizawa, A., et al.[2023]

In a study of 46 patients with metastatic renal cell carcinoma treated with nivolumab plus ipilimumab, 72% experienced immune-related adverse events (irAEs), which were linked to significantly longer progression-free survival (PFS) compared to those without irAEs.

While irAE development was an independent predictor of longer PFS, it did not affect overall survival (OS), suggesting that irAEs could serve as a useful prognostic marker for treatment outcomes in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prognostic impact of immune-related adverse events in metastatic renal cell carcinoma treated with nivolumab plus ipilimumab. Ikeda, T., Ishihara, H., Nemoto, Y., et al.[2022]

In a study of 35 patients with advanced renal cell carcinoma treated with nivolumab plus ipilimumab, 62.9% experienced immune-related adverse events, which were associated with significantly longer progression-free and overall survival rates.

The presence of immune-related adverse events, particularly skin reactions, was identified as an independent predictor of better clinical outcomes, suggesting that these events could serve as effective biomarkers for treatment response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immune-related adverse events are clinical biomarkers to predict favorable outcomes in advanced renal cell carcinoma treated with nivolumab plus ipilimumab. Ueda, K., Suekane, S., Kurose, H., et al.[2022]

In a real-world study of 195 patients with metastatic renal cell carcinoma (mRCC) treated with ipilimumab plus nivolumab, the estimated median overall survival was 54.5 months, indicating a significant survival benefit similar to that seen in clinical trials.

The treatment was generally well-tolerated, but 45% of patients discontinued due to disease progression and 18% due to toxicity, with colitis being the most common adverse event, highlighting the importance of monitoring for side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Utilization and Safety of Ipilimumab Plus Nivolumab in a Real-World Cohort of Metastatic Renal Cell Carcinoma Patients. Thana, M., Basappa, NS., Ghosh, S., et al.[2022]

Nivolumab combined with ipilimumab significantly improves overall survival in adult patients with intermediate/poor-risk advanced renal cell carcinoma compared to sunitinib, with a hazard ratio of 0.63, indicating a 37% reduction in the risk of death.

In the study involving 1096 patients, the median overall survival was not reached for the nivolumab + ipilimumab group, while it was 25.95 months for the sunitinib group, highlighting the potential of this combination therapy for better long-term outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

European Medicines Agency extension of indication to include the combination immunotherapy cancer drug treatment with nivolumab (Opdivo) and ipilimumab (Yervoy) for adults with intermediate/poor-risk advanced renal cell carcinoma. Ali, S., Camarero, J., Hennik, P., et al.[2021]

The combination of nivolumab and ipilimumab, which targets PD-1 and CTLA-4 pathways, is an approved frontline therapy for metastatic clear-cell renal cell carcinoma (mccRCC).

This case study demonstrates the safe and effective use of this combination therapy in a 53-year-old patient with mccRCC and end-stage renal disease (ESRD) on hemodialysis, highlighting its potential applicability in populations often excluded from clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safe and effective use of nivolumab plus ipilimumab in a patient with metastatic clear-cell renal cell carcinoma with sarcomatoid dedifferentiation and end stage renal disease on hemodialysis. Shaw, LK., Wiele, AJ., Sircar, K., et al.[2022]

References

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

Tumor antigens and immune subtypes guided mRNA vaccine development for kidney renal clear cell carcinoma. [2022]

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

Collection of real-world data on nivolumab's effectiveness in renal cell carcinoma: rationale for an observational study. [2018]

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

Immunogenicity in renal cell carcinoma: shifting focus to alternative sources of tumour-specific antigens. [2023]

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

Simultaneous expression of T-cell activating antigens in renal cell carcinoma: implications for specific immunotherapy. [2019]

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

A new age for vaccine therapy in renal cell carcinoma. [2022]

6. Australia pubmed.ncbi.nlm.nih.gov

Efficacy and safety of first-line nivolumab plus ipilimumab in patients with metastatic renal cell carcinoma: A multicenter retrospective study. [2021]

7. France pubmed.ncbi.nlm.nih.gov

Comparison of the Impact of Immune-Related Adverse Events Due to Immune Checkpoint Inhibitor Dual Combination Therapy and Immune Checkpoint Inhibitor Plus Tyrosine Kinase Inhibitor Combination Therapy in Patients with Advanced Renal Cell Carcinoma. [2023]

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

Prognostic Impact of Immune-Related Adverse Events as First-Line Therapy for Metastatic Renal Cell Carcinoma Treated With Nivolumab Plus Ipilimumab: A Multicenter Retrospective Study. [2023]

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

Prognostic impact of immune-related adverse events in metastatic renal cell carcinoma treated with nivolumab plus ipilimumab. [2022]

10. England pubmed.ncbi.nlm.nih.gov

Immune-related adverse events are clinical biomarkers to predict favorable outcomes in advanced renal cell carcinoma treated with nivolumab plus ipilimumab. [2022]

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

Utilization and Safety of Ipilimumab Plus Nivolumab in a Real-World Cohort of Metastatic Renal Cell Carcinoma Patients. [2022]

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

European Medicines Agency extension of indication to include the combination immunotherapy cancer drug treatment with nivolumab (Opdivo) and ipilimumab (Yervoy) for adults with intermediate/poor-risk advanced renal cell carcinoma. [2021]

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

Safe and effective use of nivolumab plus ipilimumab in a patient with metastatic clear-cell renal cell carcinoma with sarcomatoid dedifferentiation and end stage renal disease on hemodialysis. [2022]

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

Standard Versus Modified Ipilimumab, in Combination With Nivolumab, in Advanced Renal Cell Carcinoma: A Randomized Phase II Trial (PRISM). [2023]

15. England pubmed.ncbi.nlm.nih.gov

Nivolumab for the Treatment of Patients with Metastatic Non-Clear Cell Renal Cell Carcinoma (nccRCC): A Single-Institutional Experience and Literature Meta-Analysis. [2021]