Nivolumab + Ipilimumab for Kidney Cancer

Recruiting at 159 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Bristol-Myers Squibb

Must not be taking: Anti-PD-1, Anti-PD-L1

Disqualifiers: CNS metastases, Autoimmune disease, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

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

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

437 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

The purpose of this study is to test the effectiveness and safety of nivolumab combined with ipilimumab compared to nivolumab monotherapy in participants with previously untreated kidney cancer that has spread.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. Please consult with the trial coordinators for more details.

Is the combination of Nivolumab and Ipilimumab safe for treating kidney cancer?

The combination of Nivolumab (Opdivo) and Ipilimumab (Yervoy) can cause immune-related adverse events (side effects where the immune system attacks normal organs and tissues), which have been observed in patients with kidney cancer. These side effects vary but are important to monitor during treatment. ^{1 2 3 4 5}

How is the drug combination of nivolumab and ipilimumab unique for treating kidney cancer?

The combination of nivolumab and ipilimumab is unique for treating advanced kidney cancer because it uses two immune checkpoint inhibitors to enhance the body's immune response against cancer cells, and it has shown improved survival rates compared to the standard treatment with sunitinib, especially in patients with intermediate or poor risk. ^{6 7 8 9 10}

What data supports the effectiveness of the drug combination Nivolumab and Ipilimumab for kidney cancer?

Research shows that the combination of Nivolumab and Ipilimumab has been effective in improving survival for patients with advanced kidney cancer, particularly in those who have not received prior treatment. Studies have demonstrated that this drug combination can lead to better outcomes compared to other treatments like Sunitinib. ^{1 8 9 11 12}

Who Is on the Research Team?

Bristol-Myers Squibb

Principal Investigator

Bristol-Myers Squibb

Are You a Good Fit for This Trial?

This trial is for adults with advanced kidney cancer that can't be removed by surgery or treated with radiation. They should not have had any previous systemic treatments for their cancer, must show measurable signs of the disease on scans, and be classified as having an intermediate or poor prognosis.

Inclusion Criteria

I have not had any drug treatments for kidney cancer.

My kidney cancer cannot be cured with surgery or radiation.

My cancer can be measured on scans according to specific criteria.

Exclusion Criteria

I do not have active brain metastases.

I have been treated with specific immune system targeting drugs.

I have an autoimmune disease.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either nivolumab combined with ipilimumab or nivolumab monotherapy

12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Ipilimumab
• Nivolumab

Trial Overview The study is comparing the effectiveness of two approaches: one group will receive Nivolumab combined with Ipilimumab (both are immunotherapy drugs), while another group gets Nivolumab alone. The goal is to see which treatment works better for new kidney cancer patients.

How Is the Trial Designed?

Group I: Nivolumab + ipilimumab placebo Experimental Treatment 1 Intervention

Group II: Nivolumab + ipilimumab Experimental Treatment 2 Interventions

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?

Bristol-Myers Squibb

Lead 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

Published Research Related to This Trial

In a phase 3 trial involving 1096 patients with untreated advanced renal-cell carcinoma, nivolumab plus ipilimumab significantly improved overall survival rates (75% at 18 months) compared to sunitinib (60% at 18 months), indicating a more effective treatment option for patients with intermediate or poor prognostic risk.

The objective response rate was also higher with nivolumab plus ipilimumab (42%) compared to sunitinib (27%), although both treatments had a high incidence of treatment-related adverse events, with nivolumab plus ipilimumab showing a slightly lower rate of severe (grade 3 or 4) events (46% vs. 63%).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab plus Ipilimumab versus Sunitinib in Advanced Renal-Cell Carcinoma. Motzer, RJ., Tannir, NM., McDermott, DF., 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]

In a study of 45 Japanese patients with untreated metastatic renal cell carcinoma, the combination therapy of nivolumab and ipilimumab showed a 41.5% objective response rate and a median progression-free survival of 17.8 months over a 2-year follow-up period.

The 2-year analysis indicated that nivolumab plus ipilimumab therapy's effectiveness aligns with previous studies, and second-line therapy following this combination also demonstrated a 20% objective response rate with a median progression-free survival of 9.8 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world effectiveness of nivolumab plus ipilimumab and second-line therapy in Japanese untreated patients with metastatic renal cell carcinoma: 2-year analysis from a multicenter retrospective clinical study (J-cardinal study). Kojima, T., Kato, R., Sazuka, T., et al.[2022]

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 pooled analysis of 410 patients with advanced clear cell renal cell carcinoma, nivolumab plus ipilimumab showed a modest objective response rate of 12.6% in patients who did not respond to prior nivolumab treatment, indicating that a small subset may still benefit from this combination therapy.

The study found that the overall survival rate at three years was 59%, suggesting that while the response to salvage therapy is limited, the combination can still provide significant long-term survival benefits for some patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Pooled Analysis of 3 Phase II Trials of Salvage Nivolumab/Ipilimumab After Nivolumab in Renal Cell Carcinoma. McKay, RR., Leucht, K., Xie, W., et al.[2023]

In a real-world analysis of adverse events from two combination therapies for advanced renal cell carcinoma, cabozantinib (CAB) plus nivolumab (NIVO) showed higher incidence rates of seven types of toxicities compared to ipilimumab (IPI) plus NIVO.

Conversely, IPI + NIVO was associated with higher rates of three types of toxicities and had a greater incidence of serious adverse events, suggesting that both therapies have distinct safety profiles that can guide treatment decisions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse Events of Cabozantinib Plus Nivolumab Versus Ipilimumab Plus Nivolumab. Blas, L., Shiota, M., Tsukahara, S., et al.[2023]

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]

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]

A patient on hemodialysis with advanced clear-cell renal cell carcinoma successfully received combined immune checkpoint blockade therapy with nivolumab and ipilimumab, showing no significant immune-related adverse events.

This case supports the safety and efficacy of using nivolumab and ipilimumab in patients on hemodialysis, suggesting that renal function does not significantly impact the treatment's pharmacokinetics or safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab and ipilimumab immunotherapy for hemodialysis patients with advanced renal cell carcinoma. Kobayashi, Y., Arai, H., Honda, M.[2023]

A 73-year-old hemodialysis patient with metastatic renal cell carcinoma was treated with the combination of ipilimumab and nivolumab, which was administered safely without any adverse events.

This case suggests that ipilimumab-nivolumab can be a viable treatment option for metastatic renal cell carcinoma in patients on hemodialysis, a group that typically has limited treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safe administration of ipilimumab plus nivolumab to a dialysis patient with renal cell carcinoma. Iwaki, T., Niimi, A., Kano, M., et al.[2022]

Citations

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

Nivolumab plus Ipilimumab versus Sunitinib in Advanced Renal-Cell Carcinoma. [2022]

2. 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]

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

Real-world effectiveness of nivolumab plus ipilimumab and second-line therapy in Japanese untreated patients with metastatic renal cell carcinoma: 2-year analysis from a multicenter retrospective clinical study (J-cardinal study). [2022]

4. 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]

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

A Pooled Analysis of 3 Phase II Trials of Salvage Nivolumab/Ipilimumab After Nivolumab in Renal Cell Carcinoma. [2023]

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

Adverse Events of Cabozantinib Plus Nivolumab Versus Ipilimumab Plus Nivolumab. [2023]

7. 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]

8. 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]

9. 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]

10. 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]

11. Switzerland pubmed.ncbi.nlm.nih.gov

Nivolumab and ipilimumab immunotherapy for hemodialysis patients with advanced renal cell carcinoma. [2023]

12. Australia pubmed.ncbi.nlm.nih.gov

Safe administration of ipilimumab plus nivolumab to a dialysis patient with renal cell carcinoma. [2022]