Immunotherapy for Kidney Cancer

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Steroids, Immunosuppressants

Disqualifiers: Autoimmune disease, HIV/AIDS, Hepatitis, others

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

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

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 38

Duration: 6 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines how well the drug nivolumab (an immunotherapy) works alone or with other drugs, bevacizumab or ipilimumab, before surgery in people with metastatic kidney cancer. The goal is to determine if these treatments can help the immune system attack the cancer and prevent its growth. People with kidney cancer that can be surgically removed and has spread to other parts of the body might be suitable candidates, especially if they have experienced frequent issues related to this condition. As an Early Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants a chance to contribute to groundbreaking medical advancements.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, patients on high-dose steroids or other potent immune suppression medications, as well as those requiring ongoing anticoagulation (except aspirin), are excluded. It's best to discuss your specific medications with the trial team.

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

Research shows that nivolumab, when used alone, can cause rare but serious side effects like kidney problems, pneumonia, and diarrhea. When combined with bevacizumab, it has been tested in patients with kidney cancer and is generally well-tolerated, though bevacizumab might add more side effects.

Studies have found the combination of nivolumab and ipilimumab effective for kidney cancer, but it may also increase the risk of serious side effects, such as inflammation and issues with the liver or glands. This treatment is already approved for other uses, indicating its safety has been well-researched.

These treatments have been tested in many patients before this trial, which is an early phase trial. This trial explores new uses for these treatments, but their safety is already known in some situations. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for kidney cancer because they utilize immunotherapy, which is a different approach compared to traditional therapies like surgery or chemotherapy. Nivolumab, an immune checkpoint inhibitor, boosts the body's immune system to target cancer cells more effectively. In one arm, it's combined with bevacizumab, which inhibits blood vessel growth that tumors need to grow, offering a dual approach. Another arm combines nivolumab with ipilimumab, another immune checkpoint inhibitor, potentially providing a more robust immune response. These combinations aim to offer more precise and potentially effective treatment options with unique mechanisms compared to existing treatments.

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

Studies have shown that nivolumab, a type of immunotherapy, effectively treats advanced kidney cancer by helping the immune system attack cancer cells. In this trial, participants in Arm C will receive a combination of nivolumab and ipilimumab. Research indicates that this combination can lower the risk of death by 28% in people with untreated advanced kidney cancer. Additionally, studies show that patients receiving this combination had a 37% lower risk of dying compared to those taking sunitinib. Participants in Arm B will receive a combination of nivolumab and bevacizumab. While the effectiveness of this combination is less clear, nivolumab alone, as administered in Arm A, has shown promising long-term survival rates in patients. ^{4 5 6 7 8}

Who Is on the Research Team?

Padmanee Sharma, MD, PhD

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults with metastatic clear cell renal cell carcinoma (kidney cancer) that can be surgically removed. Participants must understand the study and risks, may have had previous treatments except certain immunotherapies or bevacizumab, and should meet specific health criteria like adequate blood counts and organ function.

Inclusion Criteria

I have had treatments for kidney cancer but not with PD1 or CTLA-4 inhibitors or bevacizumab.

My kidney cancer has spread, and I am eligible for surgery to remove the tumor.

I have a tumor or lymph node that can be measured and meets the size requirements.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients receive nivolumab alone or in combination with bevacizumab or ipilimumab for 6 weeks, followed by surgery

6 weeks

3 visits (in-person)

Surgery

Patients undergo nephrectomy, metastasectomy, or biopsy approximately 4 weeks after treatment

1 day

1 visit (in-person)

Maintenance Therapy

Patients receive maintenance nivolumab every 4 weeks for up to 2 years if they have a clinical response or stable disease

Up to 2 years

Every 4 weeks (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 5 years

30 days, 86 days, every 3 months for 2 years, every 6 months for 1 year, then annually

What Are the Treatments Tested in This Trial?

Interventions

• Bevacizumab
• Ipilimumab
• Nivolumab

Trial Overview The trial tests how well nivolumab works alone or combined with bevacizumab or ipilimumab before surgery in patients with kidney cancer. It's an early phase I pilot study to see if these monoclonal antibodies can boost the immune system to fight cancer and prevent tumor growth.

How Is the Trial Designed?

Group I: Arm C (nivolumab, ipilimumab, surgery) Experimental Treatment 6 Interventions

Patients receive nivolumab IV over 60 minutes and ipilimumab IV over 90 minutes on day 1 every 3 weeks for 6 weeks. Patients also undergo nephrectomy, metastasectomy or biopsy as in Arm A. Beginning 4-6 weeks after surgery, patients in all arms who have clinical response, stable disease, or even slight progression of disease to therapy preoperatively, receive maintenance nivolumab IV over 60 minutes on day 1. Cycles repeat every 4 weeks for 2 years in the absence of disease progression or unacceptable toxicity.

Group II: Arm B (nivolumab, bevacizumab, surgery) Experimental Treatment 6 Interventions

Patients receive nivolumab IV over 60 minutes and bevacizumab IV over 90 minutes on day 1 every 2 weeks for 6 weeks. Patients also undergo nephrectomy, metastasectomy or biopsy as in Arm A. Beginning 4-6 weeks after surgery, patients in all arms who have clinical response, stable disease, or even slight progression of disease to therapy preoperatively, receive maintenance nivolumab IV over 60 minutes on day 1. Cycles repeat every 4 weeks for 2 years in the absence of disease progression or unacceptable toxicity.

Group III: Arm A (nivolumab, surgery) Experimental Treatment 5 Interventions

Patients receive nivolumab IV over 60 minutes on day 1 every 2 weeks for 6 weeks. Approximately 4 weeks later, patients undergo nephrectomy, metastasectomy or biopsy. Beginning 4-6 weeks after surgery, patients in all arms who have clinical response, stable disease, or even slight progression of disease to therapy preoperatively, receive maintenance nivolumab IV over 60 minutes on day 1. Cycles repeat every 4 weeks for 2 years in the absence of disease progression or unacceptable toxicity.

Nivolumab is already approved in United States, European Union, Canada, Switzerland for the following indications:

Approved in United States as Opdivo for:

• Advanced or metastatic gastric cancer
• Gastroesophageal junction cancer
• Esophageal adenocarcinoma
• Melanoma
• Non-small cell lung cancer
• Renal cell carcinoma
• Hodgkin lymphoma
• Head and neck squamous cell carcinoma
• Urothelial carcinoma
• Colorectal cancer
• Hepatocellular carcinoma
• Esophageal squamous cell carcinoma

Approved in European Union as Opdivo for:

• Melanoma
• Non-small cell lung cancer
• Renal cell carcinoma
• Hodgkin lymphoma
• Head and neck squamous cell carcinoma
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Gastroesophageal junction cancer
• Esophageal adenocarcinoma

Approved in Canada as Opdivo for:

• Melanoma
• Non-small cell lung cancer
• Renal cell carcinoma
• Hodgkin lymphoma
• Head and neck squamous cell carcinoma
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Gastroesophageal junction cancer
• Esophageal adenocarcinoma

Approved in Switzerland as Opdivo for:

• Melanoma
• Non-small cell lung cancer
• Renal cell carcinoma
• Hodgkin lymphoma
• Head and neck squamous cell carcinoma
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Gastroesophageal junction cancer
• Esophageal adenocarcinoma

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 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 53 patients with metastatic renal cell carcinoma treated with nivolumab, those who experienced immune-related adverse events (irAEs) had significantly better overall survival compared to those without irAEs, indicating a potential link between irAEs and treatment efficacy.

The study found that a lower platelet-to-lymphocyte ratio before treatment was a risk factor associated with the development of irAEs, suggesting that this ratio could be a useful predictor for monitoring patient responses to nivolumab.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Association Between Immune-related Adverse Events and Clinical Outcome Following Nivolumab Treatment in Patients With Metastatic Renal Cell Carcinoma. Kobayashi, K., Iikura, Y., Hiraide, M., et al.[2021]

Nivolumab, an immune-checkpoint inhibitor used to treat lung adenocarcinoma, can lead to autoimmune side effects, as demonstrated by a case of acute tubulointerstitial nephritis in a 67-year-old patient after three infusions.

The kidney biopsy revealed specific histological changes, including proliferation of certain immune cells, indicating that nivolumab can trigger significant immune responses that may affect organ function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tubulointerstitial nephritis as adverse effect of programmed cell death 1 inhibitor, nivolumab, showed distinct histological findings. Uchida, A., Watanabe, M., Nawata, A., et al.[2021]

Nivolumab (Opdivo®) has been established as an effective second-line treatment for metastatic renal cell carcinoma (mRCC), showing improved overall survival (26 months vs. 19.7 months) and response rates compared to Everolimus, based on the CheckMate 025 trial with 1,080 participants.

The combination of Nivolumab and Ipilimumab has demonstrated a significantly higher objective response rate (42% vs. 27%) and better overall survival in intermediate and high-risk patients compared to Sunitinib, while also improving quality of life, despite an increase in immune-related adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Immunotherapy for renal cell carcinoma - current status]. Grimm, MO., Foller, S.[2019]

This case report describes the first known instance of minimal change disease with nephrotic syndrome linked to the PD-1 inhibitor Nivolumab, occurring in a 57-year-old man after one month of treatment for metastatic squamous cell carcinoma.

Despite treatment with corticosteroids and stopping Nivolumab, the patient's kidney function and nephrotic syndrome did not improve, highlighting the need for awareness of various kidney complications associated with immune checkpoint inhibitors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Minimal change disease in a patient receiving checkpoint inhibition: Another possible manifestation of kidney autoimmunity? Vaughan, E., Connolly, E., Hui, M., et al.[2021]

A 65-year-old man with advanced renal cell carcinoma achieved a remarkable reduction in metastasis after receiving nivolumab as the fifth systemic therapy, following treatment with angiogenesis inhibitors and interferon-α.

The patient experienced a pathological complete response, with no cancer cells found after adrenalectomy, and remains healthy 20 months post-surgery, highlighting the potential efficacy of nivolumab in advanced renal cell carcinoma cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pathological complete response after nivolumab therapy following angiogenesis inhibitors in a patient with metastatic renal cell carcinoma. Hagimoto, H., Kashima, S., Doi, K., et al.[2022]

Nivolumab showed antitumor activity in patients with metastatic renal cell carcinoma (mRCC), with median overall survival rates of 18.2, 25.5, and 24.7 months across three different doses, indicating its potential effectiveness as a treatment option.

The safety profile of nivolumab was manageable, with fatigue being the most common side effect; however, no significant dose-response relationship was found in terms of progression-free survival, suggesting that the efficacy may not increase with higher doses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab for Metastatic Renal Cell Carcinoma: Results of a Randomized Phase II Trial. Motzer, RJ., Rini, BI., McDermott, DF., et al.[2022]

In a study of 91 patients with metastatic renal cell carcinoma (mRCC), nivolumab showed significant improvements in overall survival, with a median survival of 25.2 months for the highest dose (10 mg/kg) and not reached for treatment-naïve patients.

Nivolumab treatment led to substantial increases in tumor-associated lymphocytes and changes in chemokine levels, indicating its immunomodulatory effects, while no new safety concerns were identified.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunomodulatory Activity of Nivolumab in Metastatic Renal Cell Carcinoma. Choueiri, TK., Fishman, MN., Escudier, B., et al.[2022]

Nivolumab, an anti-PD-1 antibody, shows promising effects in the treatment of advanced renal cancer, indicating its potential as an effective immunotherapy option.

The manuscript highlights the role of nivolumab in harnessing the immune system to target and combat renal cancer, suggesting a new avenue for treatment in this challenging disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Nivolumab (Anti-PD-1 antibody; ONO-4538/BMS-936558) in renal cancer]. Ozono, S.[2018]

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. 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. esmoopen.com esmoopen.com/article/S2059-7029(24)01371-1/fulltext

Nivolumab in patients with advanced renal cell carcinoma ... Assuming a 1-year survival rate of 70% (based on CheckMate 025 results), we determined that a sample size of 323 patients for the nivolumab ...

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. opdivohcp.com opdivohcp.com/efficacy/rcc

Efficacy Data for Renal Cell Carcinoma (RCC) - Opdivo In patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg every 3 weeks, diabetes occurred in 2.7% (15/666) of patients, including Grade 4 (0.6%), Grade 3 (0.3%) ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5568541/

Safety and Efficacy of Nivolumab in Patients With Metastatic ... Only 12% of patients with mRCC are alive at 5 years and only 1 agent has shown an improvement in overall survival (OS) in a specific subgroup of patients, ...

7. opdivohcp.com opdivohcp.com/safety/rcc

Safety Profile for Renal Cell Carcinoma (RCC) - Opdivo The most frequent serious adverse reactions reported in ≥2% of patients were acute kidney injury, pleural effusion, pneumonia, diarrhea, and hypercalcemia. In ...

8. 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 ...