Nivolumab + Ipilimumab for Kidney Cancer

Not currently recruiting at 181 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness of two drugs, nivolumab (Opdivo) and ipilimumab (Yervoy), used together compared to nivolumab alone for individuals with metastatic kidney cancer. The goal is to determine if the combination is more effective and safe for treating this type of cancer. Individuals with kidney cancer that cannot be treated with surgery or radiation, and who have not received other treatments, might be suitable candidates for this trial. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants the opportunity to contribute to potentially groundbreaking treatment advancements.

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

Research has shown that using nivolumab and ipilimumab together can help treat advanced kidney cancer. Studies have found this combination to be generally safe, with many patients tolerating the treatment well, although some experienced side effects.

Evidence indicates that people receiving this combination had a 28% lower risk of death compared to those who did not receive it. This suggests the treatment is not only effective but also relatively safe. However, like many treatments, it can cause side effects, such as tiredness, skin rash, or diarrhea. Discussing expectations and management of potential issues with healthcare providers is important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of nivolumab and ipilimumab for kidney cancer because it targets the immune system in a unique way compared to traditional treatments. Most standard therapies for kidney cancer, like tyrosine kinase inhibitors and mTOR inhibitors, work by blocking signals that cancer cells use to grow. In contrast, nivolumab and ipilimumab are immune checkpoint inhibitors that help the body's own immune system recognize and attack cancer cells more effectively. This approach not only has the potential to improve patient outcomes but also offers a novel mechanism of action that could change how kidney cancer is treated.

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

Research has shown that using nivolumab and ipilimumab together effectively treats advanced kidney cancer. In this trial, participants will receive either the combination of nivolumab and ipilimumab or a placebo version of this combination. Studies have found that this combination lowers the risk of death by 28% in patients with untreated advanced or metastatic kidney cancer. Specifically, one study showed a 37% lower risk of dying when patients received these two drugs compared to another treatment called sunitinib. This combination also links to better long-term outcomes and survival rates. Overall, the evidence suggests that these drugs together can be a strong option for treating advanced kidney cancer. ^{1 2 4 5 6}

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 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 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 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]

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]

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]

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 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 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]

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]

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]

Citations

1. news.bms.com news.bms.com/news/details/2024/Eight-Year-Data-for-Opdivo-nivolumab-Plus-Yervoy-ipilimumab-Continue-to-Demonstrate-Longest-Survival-Benefit-vs.-Sunitinib-Reported-in-Patients-with-Previously-Untreated-Advanced-or-Metastatic-Renal-Cell-Carcinoma/default.aspx

Eight-Year Data for Opdivo (nivolumab) Plus Yervoy ... Patients with previously untreated advanced or metastatic renal cell carcinoma treated with Opdivo plus Yervoy experienced a 28% reduction in the risk of death ...

2. opdivo.com opdivo.com/advanced-kidney-cancer/clinical-trial-results/immunotherapy-combination

Clinical trial results for advanced kidney cancer (renal cell ... In the clinical trial, people given OPDIVO + YERVOY had a 37% lower risk of dying than those given SUTENT, and more than half of the people given OPDIVO + ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8975659/

Efficacy and Safety of Nivolumab for Advanced Renal Cell ... Nivolumab plus ipilimumab has been reported to be associated with improved prognosis of RCC patients [8].

4. cancernetwork.com cancernetwork.com/view/nivolumab-combo-may-show-long-term-benefits-in-advanced-rcc

Nivolumab Combo May Show Long-Term Benefits in ... Combining nivolumab (Opdivo) with ipilimumab (Yervoy) may potentially improve long-term outcomes in patients with advanced renal cell carcinoma (RCC).

5. curetoday.com curetoday.com/view/real-world-data-may-support-opdivo-plus-yervoy-efficacy-in-mrcc

Real-World Data May Support Opdivo Plus Yervoy Efficacy ... Nivolumab plus ipilimumab shows promising real-world effectiveness in intermediate- or poor-risk mRCC, with median overall survival of 38.4 ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6289271/

Ipilimumab in combination with nivolumab for the treatment of ... The 18-month OS rate in favorable-risk patients was high in both treatment arms - 88% with nivolumab plus ipilimumab vs 93% with sunitinib (p = 0.27). Notably, ...