Evolocumab + Nivolumab for Kidney Cancer

Overseen By Eric Jonasch, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Chemotherapy, Immunotherapy, others

Disqualifiers: Symptomatic brain metastases, Heart failure, 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

Compensation: Varies

Number of Visits: 1

Duration: 12 months

10 Participants Needed

Trial Summary

What is the purpose of this trial?

To learn if evolocumab and nivolumab can control metastatic and refractory renal cell carcinoma. The safety of this drug combination will also be studied.

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

The trial protocol does not specify if you must stop taking your current medications. However, you cannot receive any other systemic therapy for kidney cancer while participating in this trial. If you are on chemotherapy, immunotherapy, or other experimental cancer therapy, you must stop at least 2 weeks before starting the study treatment.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot be on any other systemic therapy for kidney cancer while participating. If you are on chemotherapy, immunotherapy, or other experimental cancer therapy, you must stop at least 2 weeks before starting the trial.

What data supports the idea that Evolocumab + Nivolumab for Kidney Cancer is an effective treatment?

The available research shows that Nivolumab, when used for advanced kidney cancer, has been effective. In a study comparing Nivolumab to another drug called everolimus, patients taking Nivolumab lived longer on average, with a median survival of 25 months compared to 19.6 months for those on everolimus. This suggests that Nivolumab is a promising option for treating kidney cancer. However, there is no specific data provided on the combination of Evolocumab and Nivolumab for kidney cancer. ^{1 2 3 4 5}

What data supports the effectiveness of the drugs Evolocumab and Nivolumab for kidney cancer?

Research shows that Nivolumab, when used for advanced kidney cancer, improved survival rates compared to another drug, everolimus, with patients living a median of 25 months compared to 19.6 months. This suggests that Nivolumab can be effective in treating kidney cancer. ^{1 2 3 4 5}

What safety data exists for Evolocumab and Nivolumab in kidney cancer treatment?

Safety data for Nivolumab, used in kidney cancer treatment, indicates that while high-grade side effects are rare, immune-mediated side effects can occur, affecting organs like the skin, liver, kidneys, gastrointestinal tract, lungs, and endocrine organs. These side effects are generally reversible with timely recognition and management, including the use of corticosteroids. Studies have shown that Nivolumab, when combined with other agents like Cabozantinib, has a manageable safety profile with appropriate prophylaxis, supportive care, and dose adjustments. However, overlapping adverse events and immune-related side effects can complicate treatment, requiring careful monitoring and management strategies. ^{6 7 8 9 10}

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

Nivolumab, used in treating kidney cancer, can cause side effects like skin issues, liver inflammation, and thyroid problems, but these are usually manageable with proper care. Serious side effects are rare, and with timely management, they are often reversible. ^{6 7 8 9 10}

Is the drug Evolocumab, Nivolumab (Repatha, Opdivo) a promising treatment for kidney cancer?

Yes, Nivolumab, which is part of the treatment, has shown promising results in improving survival rates for kidney cancer patients. It has been proven to help patients live longer compared to other treatments, making it a promising option for kidney cancer. ^{2 11 12 13 14}

How is the drug combination of Evolocumab and Nivolumab unique for kidney cancer?

This treatment is unique because it combines Evolocumab, a drug typically used to lower cholesterol, with Nivolumab, an immune checkpoint inhibitor that helps the immune system attack cancer cells. This novel combination aims to enhance the immune response against kidney cancer, which is different from standard treatments that usually focus on either immune therapy or other cancer drugs alone. ^{2 11 12 13 14}

Research Team

Eric Jonasch, MD

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

This trial is for patients with metastatic renal cell carcinoma, a type of kidney cancer that has spread and doesn't respond to treatment. Participants should meet specific health criteria set by the researchers but these aren't detailed here.

Inclusion Criteria

Signed and dated IRB/IEC approved written informed consent form

My organs and bone marrow are working well.

My hepatitis B virus is undetectable with treatment.

Exclusion Criteria

I have recovered from cancer treatment side effects, except for hair loss or hormone issues.

I don't have any health issues that would interfere with the treatment.

Known hypersensitivity to study drugs or excipients

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive evolocumab and nivolumab on Day 1 of each cycle (every 4 weeks). Evolocumab is given as an injection under the skin, and nivolumab is given by vein over about 60 minutes.

12 months

1 visit per cycle (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Evolocumab
• Nivolumab

Trial Overview The study tests whether combining two drugs, Evolocumab and Nivolumab, can manage advanced kidney cancer effectively. It also examines the safety profile of this drug combination in treating the disease.

Participant Groups

Group I: Evolocumab + Nivolumab Experimental Treatment 2 Interventions

If you are found to be eligible to take part in this study, you will receive evolocumab and nivolumab on Day 1 of each cycle (every 4 weeks). Evolocumab will be given as an injection under the skin. Nivolumab will be given by vein over about 60 minutes.

Evolocumab is already approved in United States, European Union for the following indications:

Approved in United States as Repatha for:

• To reduce the risk of myocardial infarction, stroke, and coronary revascularization in adults with established cardiovascular disease
• Familial hypercholesterolemia
• High-risk patients with LDL-C ≥70 mg/dL or non-HDL-C ≥100 mg/dL on maximally tolerated statin therapy ± ezetimibe

Approved in European Union as Repatha for:

• Primary hypercholesterolaemia and mixed dyslipidaemia
• Homozygous familial hypercholesterolaemia

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

Bristol-Myers Squibb

Industry 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

Cancer Prevention Research Institute of Texas

Collaborator

Trials

55

Recruited

98,900+

United States Department of Defense

Collaborator

Trials

940

Recruited

339,000+

Findings from Research

Nivolumab, when combined with ipilimumab, significantly improves overall survival (OS) and progression-free survival (PFS) in patients with advanced renal cell carcinoma (RCC), based on a meta-analysis of three high-quality randomized controlled trials involving 2550 patients.

The treatment with nivolumab did not lead to an increase in adverse events, indicating a manageable safety profile for patients undergoing this therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Nivolumab for Advanced Renal Cell Carcinoma: A Systematic Review and Meta-Analysis. Zhang, S., Xu, X., Chen, J., et al.[2022]

Nivolumab, an immune checkpoint inhibitor, significantly improves median overall survival in advanced kidney cancer patients, achieving 25 months compared to 19.6 months with everolimus, as shown in a recent clinical trial.

The trial demonstrated a hazard ratio for death of 0.73 for nivolumab, indicating a 27% reduction in the risk of death compared to everolimus, highlighting the effectiveness of nivolumab in treating metastatic kidney cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The promising role of nivolumab in renal cell cancers. Gupta, K., Tiu, DY., Tiu, J., 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]

Nivolumab monotherapy showed limited efficacy in treatment-naïve patients with non-clear cell renal cell carcinoma (nccRCC), achieving an objective response rate of only 14.3%, with most responses occurring in patients with sarcomatoid or unclassified tumors.

Salvage therapy with nivolumab/ipilimumab after nivolumab monotherapy resulted in minimal activity, with only one partial response observed among 17 patients, and significant treatment-related adverse events were reported, indicating a need for careful patient selection and monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II study of nivolumab and salvage nivolumab/ipilimumab in treatment-naïve patients with advanced non-clear cell renal cell carcinoma (HCRN GU16-260-Cohort B). Atkins, MB., Jegede, OA., Haas, NB., et al.[2023]

In a study of 33 patients with metastatic non-clear cell renal cell carcinoma, the combination therapy of ipilimumab and nivolumab showed a longer median overall survival (19.6 months) compared to molecular targeted therapy (10.6 months), although this difference was not statistically significant.

The combination therapy also resulted in a significantly higher objective response rate of 30% compared to 4.5% for molecular targeted therapy, indicating that ipilimumab plus nivolumab may be more effective in eliciting a response in patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative Efficacy of Combination Therapy of Ipilimumab Plus Nivolumab for Non-clear Cell Renal Cell Carcinoma. Bando, Y., Furukawa, J., Okamura, Y., et al.[2022]

In a study of 389 patients with metastatic renal cell cancer (mRCC) treated with nivolumab, the treatment showed a 23.1% objective response rate and a median progression-free survival of 4.5 months, indicating its efficacy in this patient population.

The safety profile was favorable, with no treatment-related deaths and only 5.7% of patients discontinuing treatment due to adverse events, suggesting that nivolumab is a safe option for patients, including those who are elderly or have previously received multiple therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of nivolumab for metastatic renal cell carcinoma: real-world results from an expanded access programme. De Giorgi, U., Cartenì, G., Giannarelli, D., et al.[2022]

Nivolumab is the first PD-1 receptor inhibitor approved for treating metastasized renal cell carcinoma, requiring careful monitoring for side effects due to its immunotherapy nature.

While serious side effects (grades 3 or 4) are rare, they can affect various organs and may require treatment adjustments; however, with timely recognition and management, these immune-mediated side effects are generally reversible.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Therapy monitoring and management of adverse events in PD-1/PD-L1 immune checkpoint inhibition]. Oppel-Heuchel, H., Grimm, MO.[2018]

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]

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]

The combination of cabozantinib (a tyrosine kinase inhibitor) and nivolumab (an immune checkpoint inhibitor) significantly improved progression-free survival, overall survival, and objective response rates in patients with untreated advanced renal cell carcinoma compared to sunitinib, supporting its approval as a first-line therapy.

While the safety profile of the combination treatment is generally manageable, it requires careful monitoring and management of overlapping adverse events, such as diarrhea and hepatotoxicity, to maintain patient tolerability and treatment effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Management of adverse events associated with cabozantinib plus nivolumab in renal cell carcinoma: A review. McGregor, B., Mortazavi, A., Cordes, L., et al.[2023]

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, an anti-PD1 immune checkpoint inhibitor, has significantly improved overall survival rates for patients with first-line metastatic renal cell carcinoma since its introduction in 2015.

The combination of nivolumab with ipilimumab is expected to revolutionize treatment strategies for metastatic renal cell carcinoma, indicating a major shift in clinical management approaches.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Immunotherapy in renal cell carcinoma: A booming clinical research]. Baize, N., Bigot, P.[2019]

In a study of 90 patients with metastatic clear cell renal cell carcinoma treated with nivolumab, the median overall survival was 15.8 months, while the median progression-free survival was 4.4 months, indicating that nivolumab can provide a significant duration of benefit for some patients.

The study identified that a higher baseline Neutrophil-to-Lymphocyte ratio (NLR) was linked to an increased risk of disease progression, while a higher baseline eosinophil count was associated with a lower risk, suggesting these markers could help predict patient outcomes on nivolumab.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patterns, predictors and subsequent outcomes of disease progression in metastatic renal cell carcinoma patients treated with nivolumab. Zahoor, H., Barata, PC., Jia, X., et al.[2019]

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]

References

1. Egypt pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Nivolumab for Advanced Renal Cell Carcinoma: A Systematic Review and Meta-Analysis. [2022]

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

The promising role of nivolumab in renal cell cancers. [2022]

3. Japan pubmed.ncbi.nlm.nih.gov

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

4. England pubmed.ncbi.nlm.nih.gov

Phase II study of nivolumab and salvage nivolumab/ipilimumab in treatment-naïve patients with advanced non-clear cell renal cell carcinoma (HCRN GU16-260-Cohort B). [2023]

5. Greece pubmed.ncbi.nlm.nih.gov

Comparative Efficacy of Combination Therapy of Ipilimumab Plus Nivolumab for Non-clear Cell Renal Cell Carcinoma. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Safety and efficacy of nivolumab for metastatic renal cell carcinoma: real-world results from an expanded access programme. [2022]

7. Germany pubmed.ncbi.nlm.nih.gov

[Therapy monitoring and management of adverse events in PD-1/PD-L1 immune checkpoint inhibition]. [2018]

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

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

9. Japan pubmed.ncbi.nlm.nih.gov

Tubulointerstitial nephritis as adverse effect of programmed cell death 1 inhibitor, nivolumab, showed distinct histological findings. [2021]

10. Netherlands pubmed.ncbi.nlm.nih.gov

Management of adverse events associated with cabozantinib plus nivolumab in renal cell carcinoma: A review. [2023]

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

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

12. France pubmed.ncbi.nlm.nih.gov

[Immunotherapy in renal cell carcinoma: A booming clinical research]. [2019]

13. England pubmed.ncbi.nlm.nih.gov

Patterns, predictors and subsequent outcomes of disease progression in metastatic renal cell carcinoma patients treated with nivolumab. [2019]

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

Nivolumab for Metastatic Renal Cell Carcinoma: Results of a Randomized Phase II Trial. [2022]