Nivolumab + Ipilimumab for Kidney Cancer

Recruiting at 387 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Bristol-Myers Squibb

Must not be taking: VEGF inhibitors, Corticosteroids

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: 5

Duration: Until disease progression or study end

1390 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

The purpose of this study is to compare the objective response rate, progression free survival and the overall survival of Nivolumab combined with Ipilimumab to Sunitinib monotherapy in patients with previously untreated Renal Cell Cancer.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are on systemic corticosteroids or immunosuppressive medications, you may need to stop them 14 days before starting the study drug.

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

The combination of Nivolumab (Opdivo) and Ipilimumab (Yervoy) has been studied for safety in treating advanced kidney cancer. Some patients may experience immune-related side effects, which are reactions where the immune system attacks normal organs and tissues, but these are generally manageable with medical care. ^{1 2 3 4 5}

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

The combination of nivolumab and ipilimumab is unique for treating advanced kidney cancer because it is an immunotherapy that works by helping the immune system attack cancer cells more effectively, and it has shown better and longer-lasting responses compared to the standard drug sunitinib, with fewer side effects. ^{2 6 7 8 9}

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

Research shows that the combination of Nivolumab and Ipilimumab is more effective than Sunitinib for treating advanced kidney cancer, with more patients responding to the treatment and experiencing longer periods without the disease getting worse. ^{2 6 8 9 10}

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 or metastatic renal cell carcinoma who haven't had systemic therapy for it, except possibly one adjuvant/neoadjuvant therapy not targeting VEGF if recurrence was over 6 months ago. Participants must have a KPS of at least 70%, measurable disease, and provide tumor tissue samples. Exclusions include brain metastases, prior VEGF/VEGF receptor targeted therapies or immunotherapies, current CNS metastases, and certain autoimmune diseases.

Inclusion Criteria

I am able to care for myself but may not be able to do active work.

My kidney cancer cannot be cured with surgery or radiation.

My kidney cancer diagnosis includes clear-cell features.

Exclusion Criteria

I have previously been treated with specific immunotherapy drugs.

I have had or currently have cancer spread to my brain.

I don't have an active autoimmune disease or need strong immune system medications.

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 Sunitinib monotherapy. Nivolumab and Ipilimumab are administered intravenously every 3 weeks for 4 doses, followed by Nivolumab every 2 weeks. Sunitinib is taken orally for 4 weeks followed by 2 weeks off.

Until disease progression or study end

Every 2-3 weeks (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment. Survival follow-up is conducted every 3 months.

Approximately 31 months

Every 3 months (in-person or virtual)

Open-label extension (optional)

Eligible participants may switch from Sunitinib to Nivolumab combined with Ipilimumab after completion of the final analysis.

Long-term

What Are the Treatments Tested in This Trial?

Interventions

• Ipilimumab
• Nivolumab
• Sunitinib

Trial Overview The study compares the effectiveness of combining Nivolumab (an immune checkpoint inhibitor) with Ipilimumab (another immune-modulating drug) against Sunitinib monotherapy in untreated renal cell cancer patients. It looks at response rate to treatment, how long patients live without their disease getting worse, and overall survival rates.

How Is the Trial Designed?

Group I: Arm A: Nivolumab 3 mg/kg + Ipilimumab 1 mg/kg Experimental Treatment 2 Interventions

Nivolumab 3 mg/kg combined with Ipilimumab 1 mg/kg solutions intravenously every 3 weeks for 4 doses then Nivolumab 3 mg/kg solutions intravenously every 2 weeks until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends

Group II: Arm B: Sunitinib 50 mg Active Control 3 Interventions

Sunitinib 50 mg capsules by mouth once daily for 4 weeks then 2 weeks off, continuously until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends After completion of final analysis eligible participants may switch from receiving Sunitinib to receiving Nivolumab 3 mg/kg IV combined with Ipilimumab 1 mg/kg IV every 3 weeks for 4 doses then Nivolumab 240mg flat dose IV every 2 weeks

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

Ono Pharmaceutical Co. Ltd

Industry Sponsor

Trials

182

Recruited

97,100+

Shinji Takai

Ono Pharmaceutical Co. Ltd

Chief Medical Officer since 2023

MD from an unspecified institution

Gyo Sagara

Ono Pharmaceutical Co. Ltd

Chief Executive Officer since 2024

PhD in Pharmaceutical Sciences from Kyoto University

Published Research Related to This Trial

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 phase III trial, the combination of nivolumab and ipilimumab resulted in a higher response rate (over 41%) compared to sunitinib (26.5%) in patients with intermediate or high-risk renal cell carcinoma.

Patients treated with the immunotherapy combination not only had longer progression-free survival but also experienced fewer side effects, indicating a potentially safer and more effective treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Checkpoint Inhibitor Combo Effective for RCC. [2019]

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 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]

Sunitinib has a similar safety profile in patients undergoing nephrectomy for kidney cancer, whether used in the adjuvant setting or for metastatic disease, based on data from phase III trials including CARMENA and SURTIME.

Effective management of sunitinib's adverse effects is crucial, particularly in the adjuvant setting, where maintaining dose intensity and exposure can impact treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of sunitinib in patients with renal cell carcinoma following nephrectomy. Heraudet, L., Domblides, C., Daste, A., et al.[2022]

In a phase 3 trial involving 651 patients with untreated advanced renal-cell carcinoma, the combination of nivolumab and cabozantinib significantly improved progression-free survival (16.6 months) compared to sunitinib (8.3 months), with a hazard ratio of 0.51, indicating a 49% reduction in the risk of disease progression or death.

Patients receiving nivolumab plus cabozantinib also had a higher overall survival rate at 12 months (85.7%) compared to those on sunitinib (75.6%), and a greater objective response rate (55.7% vs. 27.1%), although adverse events were common in both groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab plus Cabozantinib versus Sunitinib for Advanced Renal-Cell Carcinoma. Choueiri, TK., Powles, T., Burotto, M., et al.[2022]

Citations

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

Second-line targeted therapies after nivolumab-ipilimumab failure in metastatic renal cell carcinoma. [2021]

2. 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]

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

Checkpoint Inhibitor Combo Effective for RCC. [2019]

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

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

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

Nivolumab plus ipilimumab versus sunitinib in previously untreated advanced renal-cell carcinoma: analysis of Japanese patients in CheckMate 214 with extended follow-up. [2020]

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

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

7. Switzerland pubmed.ncbi.nlm.nih.gov

Balancing the Risk-Benefit Ratio of Immune Checkpoint Inhibitor and Anti-VEGF Combination Therapy in Renal Cell Carcinoma: A Systematic Review and Meta-Analysis. [2022]

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. England pubmed.ncbi.nlm.nih.gov

Safety of sunitinib in patients with renal cell carcinoma following nephrectomy. [2022]

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

Nivolumab plus Cabozantinib versus Sunitinib for Advanced Renal-Cell Carcinoma. [2022]