Nivolumab + Ipilimumab for Kidney Cancer

No longer recruiting at 442 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two treatments for advanced kidney cancer that has not been treated with other drugs. One group will receive a combination of Nivolumab (Opdivo) and Ipilimumab (Yervoy), while the other group will take Sunitinib alone. The main goal is to determine which treatment helps patients live longer and prevents cancer progression. Individuals with kidney cancer that cannot be cured with surgery or radiation and who have not taken similar drugs before may be suitable for this trial. As a Phase 3 trial, this study represents the final step before FDA approval, offering patients access to potentially life-extending treatments.

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

Research shows that the combination of Nivolumab and Ipilimumab is generally well-tolerated by patients with advanced kidney cancer. Studies have found that this treatment can significantly lower the risk of death compared to Sunitinib. Some side effects, such as tiredness and diarrhea, have been reported, but these are common with many cancer treatments.

In one study, patients taking Nivolumab and Ipilimumab had a lower risk of dying, with more than half experiencing a survival benefit. This indicates that the treatment is not only effective but also manageable for most patients.

While every treatment has potential risks, current data supports the safety of using Nivolumab and Ipilimumab together. Discuss any concerns with a healthcare provider before joining a trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for kidney cancer?

Researchers are excited about Nivolumab combined with Ipilimumab for kidney cancer because this combination offers a unique approach by using two different immune checkpoint inhibitors to enhance the body's immune response against cancer cells. Unlike the standard care options like Sunitinib, which is a tyrosine kinase inhibitor, this duo specifically targets the PD-1 and CTLA-4 pathways to unleash a more robust immune attack on the tumor. This mechanism has the potential to offer better outcomes for patients by providing a long-lasting immune response and improved survival rates. Additionally, the potential to switch from Sunitinib to the Nivolumab and Ipilimumab combination offers flexibility in treatment strategy, which could be advantageous for patient care.

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 in Arm A will receive this combination, which studies have found to result in a 28% lower risk of death compared to those in Arm B, who will receive only Sunitinib. Specifically, those on the Nivolumab and Ipilimumab treatment demonstrated a 37% lower risk of death overall. This combination also extended patients' lives, with an average survival time of 49 months. These findings suggest that the Nivolumab and Ipilimumab combination holds promise for improving outcomes in kidney cancer patients. ^{1 2 3 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 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

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 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 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 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]

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]

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 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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39705641/

Real-World Outcomes in Patients With Metastatic Renal ... This study provides data to support the understanding of the real-world utilization and long-term effectiveness of 1L NIVO + IPI in patients ...

2. 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 ...

3. ascopubs.org ascopubs.org/doi/10.1200/CCI.24.00132

Real-World Outcomes in Patients With Metastatic Renal ... This study provides data to support the understanding of the real-world utilization and long-term effectiveness of 1L NIVO + IPI in patients with I/P-risk mRCC.

4. 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 + ...

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38251783/

Real-world outcomes of nivolumab plus ipilimumab ... Regarding an effectiveness profile, median progression-free survival, time to treatment failure and overall survival were 9.01, 12.5 and 49.0 ...

6. jitc.bmj.com jitc.bmj.com/content/13/2/e010958

Efficacy and safety of nivolumab plus ipilimumab in ... Similarly, the median PFS was 4.3 months (95% CI: 1.4 – NE) for nephrectomy patients and 5.1 months (95% CI: 2.3 to 9.6) for those without ...