Nivolumab + Ipilimumab for Kidney Cancer

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

Must not be taking: High dose steroids

Disqualifiers: Other malignancies, Autoimmune disease, HIV, Hepatitis, others

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

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: Up to 2 years

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of two immunotherapy drugs, nivolumab and ipilimumab, to evaluate their effectiveness in treating kidney cancer. The goal is to help the immune system attack cancer cells and prevent their growth and spread. This trial may suit individuals with advanced kidney cancer who have not received certain types of immunotherapy before. Participants should have a measurable tumor and show signs of disease progression after their last treatment. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group of people.

Do I have to stop taking my current medications for the trial?

The trial does not specify if you need to stop taking your current medications. However, you cannot be on high-dose steroids or other potent immune suppression medications, and you must not be receiving any other systemic therapy for kidney cancer.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research shows that using nivolumab and ipilimumab together is safe for treating kidney cancer. Studies have found that while patients may experience some side effects, they are usually manageable.

In one study, patients with metastatic renal cell carcinoma (a type of kidney cancer that has spread) had positive long-term results. The treatment's safety matched existing knowledge, with side effects similar to those seen in other studies of these drugs. Common side effects include tiredness, skin rash, or diarrhea, which are typical for these kinds of treatments.

Overall, research suggests that the combination of nivolumab and ipilimumab is generally well-tolerated. This should reassure those considering joining a clinical trial about the treatment's safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about the combination of Nivolumab and Ipilimumab for kidney cancer because these drugs work differently from standard treatments. Unlike traditional options that primarily target cancer cells directly, Nivolumab and Ipilimumab are immunotherapies that enhance the body's own immune system to recognize and attack cancer cells. Nivolumab blocks the PD-1 pathway, and Ipilimumab targets CTLA-4, both of which are immune checkpoints that cancers use to evade detection. This unique mechanism can potentially offer improved outcomes by harnessing the immune system more effectively.

What evidence suggests that nivolumab and ipilimumab might be an effective treatment for kidney cancer?

Research shows that the combination of nivolumab and ipilimumab, which participants in this trial will receive, can effectively treat kidney cancer. In everyday medical practice, patients using this combination have lived without their cancer worsening for an average of 9 months and have lived for an average of 49 months overall. Another study found that this treatment worked for 70% of patients in certain groups. These findings suggest that nivolumab and ipilimumab can help the immune system fight kidney cancer and slow its growth. ^{1 2 3 6 7}

Who Is on the Research Team?

Nizar Tannir

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for patients with kidney cancer, specifically Renal Medullary Carcinoma. Participants can be new to treatment or have had previous therapies, must not be HIV positive or pregnant, and should not have other severe medical conditions. They need a good performance status (able to carry out daily activities) and acceptable blood test results.

Inclusion Criteria

Your blood clotting tests should not be more than 1.5 times higher than the normal range before joining the study.

Azoospermic males and WOCBP who are continuously not heterosexually active are exempt from contraceptive requirements

Your blood must have enough white blood cells called neutrophils.

Exclusion Criteria

Patients who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study

Patients must not be scheduled to receive another experimental drug while on this study

I have not had major surgery or significant injury in the last 4 weeks.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive nivolumab and ipilimumab intravenously. Treatment repeats every 21 days for up to 4 courses, followed by nivolumab every 28 days for up to 2 years.

Up to 2 years

Follow-up

Participants are monitored for safety and effectiveness after treatment completion every 3 months.

Up to 2 years

What Are the Treatments Tested in This Trial?

Interventions

• Nivolumab and Ipilimumab

Trial Overview The trial is testing the combination of two immunotherapy drugs: Nivolumab and Ipilimumab. These drugs are designed to help the immune system recognize and fight cancer cells in patients with advanced kidney cancer.

How Is the Trial Designed?

Group I: Treatment (nivolumab, ipilimumab) Experimental Treatment 2 Interventions

Patients receive nivolumab IV over 60 minutes and ipilimumab IV over 90 minutes on day 1. Treatment repeats every 21 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. Patients then receive nivolumab IV over 60 minutes on day 1. Courses repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity.

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

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 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 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 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]

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. 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.

3. 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 ...

4. annalsofoncology.org annalsofoncology.org/article/S0923-7534(24)01516-3/fulltext

Nivolumab plus ipilimumab versus sunitinib for first-line ... Nivolumab plus ipilimumab versus sunitinib for first-line treatment of advanced renal cell carcinoma: extended 8-year follow-up results of efficacy and safety

5. nature.com nature.com/articles/s41698-025-00912-x

Enhanced efficacy of ipilimumab plus nivolumab in ... The BIONIKK trial revealed that ipilimumab plus nivolumab (Ipi/Nivo) achieved a 70% objective response rate in angiogenic cluster1/2 versus 41% in cluster4/5.

6. nejm.org nejm.org/doi/full/10.1056/NEJMoa1712126

Nivolumab plus Ipilimumab versus Sunitinib in Advanced ... Nivolumab plus ipilimumab produced objective responses in patients with advanced renal-cell carcinoma in a pilot study.

7. 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 ...