Cabozantinib + Nivolumab + Ipilimumab for Kidney Cancer

Recruiting at 3 trial locations

Overseen By Bradley McGregor, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Bradley A. McGregor, MD

Must not be taking: Corticosteroids, Hydroxychloroquine, Warfarin, others

Disqualifiers: Untreated brain metastases, Cardiovascular disorders, Autoimmune disease, 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: 12

Duration: 21 months

60 Participants Needed

Trial Summary

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you must stop all current medications. However, you cannot take certain medications like small molecule tyrosine kinase inhibitors, hydroxychloroquine, or systemic immunosuppressive medications within two weeks of starting the trial. It's best to discuss your specific medications with the trial team.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, certain medications like small molecule tyrosine kinase inhibitors, hydroxychloroquine, and some systemic immunosuppressive medications must be stopped at least 2 weeks before starting the trial. It's best to discuss your current medications with the trial team.

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

The available research shows that the combination of Cabozantinib, Nivolumab, and Ipilimumab is being explored as a potential treatment for kidney cancer. The COSMIC-313 trial compared this combination to another treatment option and suggested that using all three drugs together could be a promising approach for patients with advanced kidney cancer. This trial is considered a significant step forward in finding effective treatments for this condition. ^{1 2 3 4 5}

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

The COSMIC-313 trial suggests that the combination of cabozantinib, nivolumab, and ipilimumab could be a promising treatment option for metastatic clear cell renal cell carcinoma, as it marks a significant step forward in using triplet drug combinations for this condition. ^{1 2 3 4 5}

What safety data exists for the combination of Cabozantinib, Nivolumab, and Ipilimumab in kidney cancer treatment?

The safety of Cabozantinib plus Nivolumab has been evaluated in several studies. The CheckMate 9ER study found that this combination had a manageable safety profile with appropriate management strategies like prophylaxis, supportive care, and dose adjustments. Common adverse events included diarrhea, elevated amylase/lipase, hepatotoxicity, dermatologic reactions, fatigue, endocrine disorders, and nephrotoxicity. However, the safety of the combination of Cabozantinib, Nivolumab, and Ipilimumab specifically is not well-documented in the provided research. ^{1 2 4 6 7}

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

The combination of Cabozantinib and Nivolumab has been studied for safety in kidney cancer, showing manageable side effects with proper care. Common issues include diarrhea, skin reactions, and fatigue, but these can often be controlled with dose adjustments and supportive treatments. ^{1 2 4 6 7}

Is the drug combination of Cabozantinib, Ipilimumab, and Nivolumab promising for kidney cancer?

Yes, the combination of Cabozantinib, Ipilimumab, and Nivolumab is promising for treating advanced kidney cancer. Studies show that Cabozantinib with Nivolumab is effective and recommended by guidelines for first-line treatment. It has shown better results in terms of survival and slowing disease progression compared to some other drug combinations. ^{1 2 5 6 8}

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

This drug combination is unique because it combines two types of treatments: immunotherapy (which helps the immune system fight cancer) and targeted therapy (which blocks specific proteins that help cancer cells grow). This approach is part of a new era in kidney cancer treatment, offering a potentially more effective option for patients with advanced stages of the disease. ^{1 2 5 6 8}

What is the purpose of this trial?

This trial is testing a combination of three drugs to see if they can slow down advanced kidney cancer that has spread. The drugs work by stopping cancer growth and helping the immune system attack the cancer. About 40 people will participate in this study.

Research Team

Bradley A McGregor, MD

Principal Investigator

Dana-Farber Cancer Institute

Eligibility Criteria

Adults with advanced or metastatic non-clear cell renal cell carcinoma (nccRCC) who haven't had certain previous treatments can join. They must be able to provide a fresh tumor biopsy, use contraception, and have normal organ/marrow function. Excluded are those with specific heart diseases, autoimmune conditions, lung fibrosis, bleeding disorders without therapeutic anticoagulation, severe infections or on strong CYP3A4 inhibitors/inducers.

Inclusion Criteria

My organ and bone marrow functions are normal.

Ability to understand and willingness to sign a written informed consent document

I will have a new tumor biopsy before starting treatment unless it's unsafe.

Exclusion Criteria

I haven't taken cancer drugs or tyrosine kinase inhibitors in the last 4 weeks.

I have a bleeding disorder not caused by blood thinners.

I have had a previous transplant of an organ or stem cells from a donor.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive Cabozantinib, Nivolumab, and Ipilimumab in cycles of 21 days for the first 4 cycles, followed by cycles of 28 days

21 months

Every 3 weeks for the first 4 cycles, then every 4 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

21 months

Every 8 weeks for the first 6 months, then every 12 weeks

Treatment Details

Interventions

• Cabozantinib
• Ipilimumab
• Nivolumab

Trial Overview The trial is testing the combination of Cabozantinib with immunotherapy drugs Nivolumab and Ipilimumab for effectiveness in slowing kidney cancer growth. Participants will receive all three medications to see if they work better together than current standard treatments.

Participant Groups

Group I: Cabozantinib Experimental Treatment 3 Interventions

Eligible patients will be enrolled and receive treatment with * Cycle 1-4 (cycles of 21 days) * Cabozantinib predetermined protocol dosage po daily * Nivolumab predetermined protocol dosage via IV every 3 weeks * Ipilimumab predetermined protocol dosage via IV every 3 weeks * After the first four cycles of therapy, * Cabozantinib determined protocol dosage po daily * Nivolumab predetermined protocol dosage via IV every 3 weeks (cycles of 28 days)

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?

Bradley A. McGregor, MD

Lead Sponsor

Trials

3

Recruited

100+

Bradley A. McGregor

Lead Sponsor

Trials

3

Recruited

100+

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

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

Findings from Research

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]

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]

A 77-year-old male with metastatic papillary renal cell carcinoma and inferior vena cava tumor thrombus was successfully treated with nivolumab plus cabozantinib, leading to significant regression of all lesions.

Following treatment, the patient underwent radical nephrectomy and other surgeries, with no viable cancer cells found and no recurrence of the disease for 9 months, indicating the potential efficacy of this combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Complete response of metastatic papillary renal cell carcinoma with inferior vena cava tumor thrombus to nivolumab plus cabozantinib. Hayashida, M., Miura, Y., Yamaguchi, T., et al.[2023]

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]

The COSMIC-313 phase 3 trial demonstrated that the triplet combination of cabozantinib, nivolumab, and ipilimumab may offer a new first-line treatment option for patients with metastatic clear cell renal cell carcinoma, marking a significant advancement in therapy.

The results presented at the 2022 European Society of Medical Oncology Congress suggest that triplet combinations could enhance treatment efficacy compared to the standard dual therapy of nivolumab and ipilimumab.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Less is More? First Impressions From COSMIC-313. Msaouel, P.[2023]

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 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]

Cabozantinib combined with nivolumab is shown to be superior in terms of progression-free survival (PFS) compared to axitinib + pembrolizumab and nivolumab + ipilimumab for the first-line treatment of metastatic clear-cell renal cell carcinoma (RCC), based on a systematic review of four randomized controlled trials involving treatment-naïve patients.

While cabozantinib + nivolumab demonstrated effectiveness, the combination of lenvatinib + pembrolizumab showed numerical superiority in overall survival, indicating that while cabozantinib + nivolumab is a strong option, other combinations may also be effective and warrant consideration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immune checkpoint inhibitors combined with tyrosine kinase inhibitors or immunotherapy for treatment-naïve metastatic clear-cell renal cell carcinoma-A network meta-analysis. Focus on cabozantinib combined with nivolumab. Niewada, M., Macioch, T., Konarska, M., et al.[2023]

References

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

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

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

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

3. Australia pubmed.ncbi.nlm.nih.gov

Complete response of metastatic papillary renal cell carcinoma with inferior vena cava tumor thrombus to nivolumab plus cabozantinib. [2023]

4. 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]

5. England pubmed.ncbi.nlm.nih.gov

Less is More? First Impressions From COSMIC-313. [2023]

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

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

7. Netherlands pubmed.ncbi.nlm.nih.gov

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

8. Switzerland pubmed.ncbi.nlm.nih.gov

Immune checkpoint inhibitors combined with tyrosine kinase inhibitors or immunotherapy for treatment-naïve metastatic clear-cell renal cell carcinoma-A network meta-analysis. Focus on cabozantinib combined with nivolumab. [2023]