Nivolumab + Cabozantinib for Kidney Cancer

(CheckMate 9ER Trial)

Recruiting at 285 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Bristol-Myers Squibb

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: Unknown

Duration: Up to 31 months

701 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to determine whether Nivolumab Combined with Cabozantinib is safe and effective compared to Sunitinib in previously untreated advanced or metastatic renal cell carcinoma

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 certain treatments like high-dose corticosteroids or other immunosuppressive drugs within 14 days before starting the trial.

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

Research shows that the combination of Nivolumab and Cabozantinib is more effective than Sunitinib alone for treating advanced kidney cancer, leading to longer survival and better quality of life for patients. This combination is approved as a first-line treatment in several countries, and studies have shown it improves progression-free survival and overall survival compared to Sunitinib. ^{1 2 3 4 5}

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

The combination of Nivolumab and Cabozantinib has been shown to have a manageable safety profile for treating advanced kidney cancer, with common side effects including diarrhea, fatigue, and skin reactions. These side effects can often be managed with supportive care and dose adjustments. ^{1 2 6 7 8}

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

The combination of Nivolumab and Cabozantinib is unique because it has shown to be more effective than Sunitinib alone for advanced kidney cancer, offering longer survival and better quality of life. This combination uses a dual approach: Nivolumab boosts the immune system to fight cancer, while Cabozantinib targets cancer cell growth pathways. ^{1 2 3 4 9}

Research Team

Bristol-Myers Squibb

Principal Investigator

Bristol-Myers Squibb

Eligibility Criteria

This trial is for adults with advanced or metastatic renal cell carcinoma (kidney cancer) who haven't had systemic treatment for it, except possibly one adjuvant therapy that didn't target VEGF. Participants should not have received certain vaccines recently, be on high-dose steroids or other immune-suppressing drugs, have active brain metastases, or any known autoimmune diseases.

Inclusion Criteria

My kidney cancer cannot be cured with surgery or radiation.

My kidney cancer has been confirmed to have clear-cell features.

I had one treatment for kidney cancer that didn't target blood vessel growth, and my cancer returned 6+ months after treatment.

Exclusion Criteria

I have active cancer spread to my brain.

I haven't taken high-dose steroids or other immune-weakening drugs in the last 2 weeks.

You have any ongoing or suspected autoimmune disease.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Nivolumab combined with Cabozantinib or Sunitinib

Up to 31 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 32 months

Open-label extension (optional)

Participants may opt into continuation of treatment long-term

Treatment Details

Interventions

• Cabozantinib
• Nivolumab
• Sunitinib

Trial Overview The study is testing the safety and effectiveness of combining Nivolumab (an immunotherapy drug) with Cabozantinib (a medication targeting cancer growth) versus using Sunitinib alone in patients who are facing kidney cancer for the first time without previous treatments.

Participant Groups

Group I: Triplet Experimental Treatment 1 Intervention

Nivolumab, Ipilimumab, Cabozantinib \*Enrollment to the triplet arm was discontinued by protocol amendment

Group II: Doublet Experimental Treatment 2 Interventions

Nivolumab and Cabozantinib

Group III: Monotherapy Active Control 1 Intervention

Sunitinib

Cabozantinib is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Cabometyx for:

• Renal cell carcinoma
• Hepatocellular carcinoma

Approved in United States as Cabometyx for:

• Renal cell carcinoma
• Hepatocellular carcinoma

Approved in Canada as Cabometyx for:

• Renal cell carcinoma
• Hepatocellular carcinoma

Approved in Japan as Cabometyx for:

• Renal cell carcinoma

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

Exelixis

Industry Sponsor

Trials

126

Recruited

20,500+

Michael M. Morrissey

Exelixis

Chief Executive Officer since 2010

PhD in Chemistry from Harvard University, BSc in Chemistry from the University of Wisconsin

Vicki L. Goodman

Exelixis

Chief Medical Officer since 2022

MD

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

Findings from Research

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 II trial involving 47 patients with advanced non-clear-cell renal cell carcinoma, the combination of cabozantinib and nivolumab showed a promising objective response rate of 47.5% in patients with papillary, unclassified, or translocation-associated RCC, along with a median progression-free survival of 12.5 months.

The treatment was less effective in chromophobe RCC, with no objective responses observed, highlighting the need for further research into genomic predictors of response, particularly mutations like NF2 and FH that were associated with better outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II Trial of Cabozantinib Plus Nivolumab in Patients With Non-Clear-Cell Renal Cell Carcinoma and Genomic Correlates. Lee, CH., Voss, MH., Carlo, MI., et al.[2023]

In a phase 3 trial involving 855 patients with untreated advanced renal-cell carcinoma, the combination of cabozantinib with nivolumab and ipilimumab significantly improved progression-free survival compared to nivolumab and ipilimumab alone, with a 12-month progression-free survival rate of 57% versus 49%.

However, the experimental group experienced a higher incidence of severe adverse events (grade 3 or 4) at 79%, compared to 56% in the control group, indicating a trade-off between efficacy and safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cabozantinib plus Nivolumab and Ipilimumab in Renal-Cell Carcinoma. Choueiri, TK., Powles, T., Albiges, L., et al.[2023]

The combination of cabozantinib (a TKI) and nivolumab (an anti-PD-1 antibody) is an effective first-line treatment for previously-untreated advanced renal cell carcinoma (RCC), showing significantly longer progression-free and overall survival compared to sunitinib monotherapy in the CheckMate 9ER trial.

Patients receiving cabozantinib plus nivolumab reported better health-related quality of life, although the combination therapy had a higher incidence of serious adverse events compared to sunitinib, indicating a need for careful monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cabozantinib plus Nivolumab: A Review in Advanced Renal Cell Carcinoma. Markham, A.[2022]

Cabozantinib (CAB) has shown significant improvements in overall survival and progression-free survival in phase-III studies for patients with advanced renal cell carcinoma and hepatocellular carcinoma, leading to its approval in Japan for these conditions.

CAB may enhance antitumor immunity and, when combined with PD-1 checkpoint inhibitors like nivolumab, has demonstrated increased progression-free survival compared to standard treatments, indicating a potential synergistic effect in cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Pharmacological properties and clinical outcomes of the anti-cancer drug, cabozantinib (CABOMETYX®)]. Osaka, T., Yamaguchi, N., Hara, T.[2022]

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 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]

The European Association of Urology now recommends nivolumab and cabozantinib as preferred treatments for patients with renal cancer who have not responded to previous vascular endothelial growth factor-targeted therapies.

Recent data indicate that cabozantinib offers a survival benefit, reinforcing its efficacy as a treatment option in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

European Association of Urology Guidelines for Clear Cell Renal Cancers That Are Resistant to Vascular Endothelial Growth Factor Receptor-Targeted Therapy. Powles, T., Staehler, M., Ljungberg, B., et al.[2018]

References

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

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

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

Phase II Trial of Cabozantinib Plus Nivolumab in Patients With Non-Clear-Cell Renal Cell Carcinoma and Genomic Correlates. [2023]

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

Cabozantinib plus Nivolumab and Ipilimumab in Renal-Cell Carcinoma. [2023]

4. France pubmed.ncbi.nlm.nih.gov

Cabozantinib plus Nivolumab: A Review in Advanced Renal Cell Carcinoma. [2022]

5. Japan pubmed.ncbi.nlm.nih.gov

[Pharmacological properties and clinical outcomes of the anti-cancer drug, cabozantinib (CABOMETYX®)]. [2022]

6. Netherlands pubmed.ncbi.nlm.nih.gov

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

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

Cabozantinib Versus Sunitinib As Initial Targeted Therapy for Patients With Metastatic Renal Cell Carcinoma of Poor or Intermediate Risk: The Alliance A031203 CABOSUN Trial. [2022]

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

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

9. Switzerland pubmed.ncbi.nlm.nih.gov

European Association of Urology Guidelines for Clear Cell Renal Cancers That Are Resistant to Vascular Endothelial Growth Factor Receptor-Targeted Therapy. [2018]