Nivolumab + Cabozantinib for Kidney Cancer

(CheckMate 9ER Trial)

Not currently recruiting at 323 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Bristol-Myers Squibb

Must not be taking: Corticosteroids, Immunosuppressants, Live vaccines

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: Unknown

Duration: Up to 31 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether a combination of two drugs, Nivolumab (an immunotherapy) and Cabozantinib (a targeted therapy), is more effective than Sunitinib for individuals with untreated advanced kidney cancer. Researchers aim to determine the safety and efficacy of this new combination. The trial includes different groups: some receive only Sunitinib, while others receive the combination treatment. It seeks participants diagnosed with advanced or metastatic kidney cancer that cannot be surgically removed. Participants should not have received certain prior treatments, particularly those targeting specific cancer growth factors. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

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.

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

Research has shown that the combination of Nivolumab and Cabozantinib for kidney cancer is generally well-tolerated. Earlier studies found this treatment to be safe and effective, with patients experiencing a lower risk of death compared to those taking Sunitinib, another kidney cancer drug. While some side effects occurred, they were usually manageable with proper care.

For the combination of Nivolumab, Ipilimumab, and Cabozantinib, studies indicate it can slow the growth of kidney cancer. However, this combination has more side effects, making it harder to tolerate. Still, its effectiveness in treating cancer may offer an advantage.

These treatments have undergone advanced research stages, suggesting they are safe enough to proceed to this point. However, as with any treatment, it is important to consider the benefits alongside possible side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Nivolumab and Cabozantinib for kidney cancer because it targets the disease in a novel way. Unlike standard treatments such as Sunitinib, which primarily inhibits tumor growth, this duo enhances the body's immune response while also blocking pathways that tumors use to grow. Nivolumab, an immune checkpoint inhibitor, works by unleashing the immune system to attack cancer cells, while Cabozantinib inhibits multiple pathways that help tumors spread. This dual-action approach holds promise for improved outcomes compared to existing therapies.

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

This trial will evaluate different treatment options for advanced kidney cancer. One arm will study the combination of nivolumab and cabozantinib. Studies have shown that this combination reduces the risk of death by 23% compared to sunitinib, which is being tested as a monotherapy in another arm. Another study found that this combination lowered the chance of cancer progression by 49%. Although enrollment in the triplet arm with nivolumab, ipilimumab, and cabozantinib has been discontinued, research indicates that adding ipilimumab can significantly slow the disease or reduce the risk of death. These findings suggest promising results for people with advanced kidney cancer using these treatments. ^{2 3 4 6 7}

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 (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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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]

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]

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 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]

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]

Citations

1. news.bms.com news.bms.com/news/details/2024/Opdivo-nivolumab-in-Combination-with-CABOMETYX-cabozantinib-Demonstrates-Long-Term-Survival-Benefits-After-Four-Years-of-Follow-Up-in-the-CheckMate--9ER-Trial-in-First-Line-Advanced-Renal-Cell-Carcinoma/default.aspx

9ER Trial in First-Line Advanced Renal Cell Carcinoma Opdivo in combination with CABOMETYX reduced the risk of death by 23% in the first-line treatment of advanced renal cell carcinoma vs. sunitinib.

2. kidneycancer.org kidneycancer.org/improved-overall-survival-in-rcc/

Opdivo plus Cabometyx improved overall RCC survival In the phase III CheckMate-9ER trial, nivolumab (Opdivo) plus cabozantinib (Cabometyx) combined improved overall survival (OS) and progression-free.

3. ir.exelixis.com ir.exelixis.com/news-releases/news-release-details/exelixis-announces-final-five-year-follow-results-checkmate-9er

9ER Trial Evaluating CABOMETYX® (cabozantinib ... - Exelixis After more than five years of follow-up, the findings demonstrated that efficacy benefits with CABOMETYX in combination with Opdivo were sustained long term.

4. opdivo.com opdivo.com/advanced-kidney-cancer/clinical-trial-results/opdivo-cabometyx-immunotherapy-combination

Clinical trial results for advanced kidney cancer (renal cell ... In a clinical trial, people given OPDIVO + CABOMETYX had a 40% lower risk of dying than those given SUTENT. Words to know.

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/35298296/

Phase II Trial of Cabozantinib Plus Nivolumab in Patients With ... Results: A total of 47 patients were treated with a median follow-up of 13.1 months. Objective response rate for cohort 1 (n = 40) was 47.5% (95 ...

6. cabometyxhcp.com cabometyxhcp.com/rcc-treatment/combo/efficacy

1L aRCC Efficacy & Safety for CABOMETYX® ... See the results from the CheckMate-9ER study - including efficacy, safety, and exploratory patient-reported quality of life data.

7. ir.exelixis.com ir.exelixis.com/news-releases/news-release-details/opdivor-nivolumab-combination-cabometyxr-cabozantinib-1

9ER Trial in First-Line Advanced Renal Cell Carcinoma Opdivo in combination with CABOMETYX reduced the risk of death by 23% in the first-line treatment of advanced renal cell carcinoma vs. sunitinib.