Cabozantinib + Nivolumab + Ipilimumab for Kidney Cancer

Recruiting in Palo Alto (17 mi)

+3 other locations

Overseen by Bradley A McGregor, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Waitlist Available

Sponsor: Bradley A. McGregor, MD

No Placebo Group

Prior Safety Data

Breakthrough Therapy

Trial Summary

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.

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.

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 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 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}

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.

Participant Groups

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.

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

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Beth Israel Deaconess Medical Center Boston, MA

UT Southwestern Medical Dallas, TX

Dana Farber Cancer Institute Boston, MA

Brigham & Woman's Hospital Boston, MA

Who Is Running the Clinical Trial?

Bradley A. McGregor, MD Lead Sponsor

Bradley A. McGregor Lead Sponsor

Bristol-Myers Squibb Industry Sponsor

Exelixis Industry Sponsor

References

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

Adverse Events of Cabozantinib Plus Nivolumab Versus Ipilimumab Plus Nivolumab. [2023] Recently, many agents and combinations for metastatic and advanced renal cell carcinoma have been approved. This study aims to highlight the comprehensive differences in adverse events (AEs) between cabozantinib (CAB) plus nivolumab (NIVO) and ipilimumab (IPI) plus NIVO based on a real-world big dataset.

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

Cabozantinib plus Nivolumab and Ipilimumab in Renal-Cell Carcinoma. [2023] The efficacy and safety of treatment with cabozantinib in combination with nivolumab and ipilimumab in patients with previously untreated advanced renal-cell carcinoma are unknown.

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] The effectiveness of nivolumab plus cabozantinib for metastatic papillary renal cell carcinoma with inferior vena cava tumor thrombus remains unclear.

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] To assess the efficacy and safety of cabozantinib plus nivolumab in a phase II trial in patients with non-clear-cell renal cell carcinoma (RCC).

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

Less is More? First Impressions From COSMIC-313. [2023] The COSMIC-313 phase 3 randomized controlled trial tested the triplet combination of cabozantinib with nivolumab and ipilimumab in comparison with nivolumab plus ipilimumab control as fist-line systemic therapy in metastatic clear cell renal cell carcinoma. The first results presented at the 2022 European Society of Medical Oncology Congress are a milestone for the renal cell carcinoma field because they signal the advent of triplet combinations as potential treatment options for our patients. The present commentary highlights some considerations and potential next steps based on these first impressions.

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

Nivolumab plus Cabozantinib versus Sunitinib for Advanced Renal-Cell Carcinoma. [2022] The efficacy and safety of nivolumab plus cabozantinib as compared with those of sunitinib in the treatment of previously untreated advanced renal-cell carcinoma are not known.

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

Management of adverse events associated with cabozantinib plus nivolumab in renal cell carcinoma: A review. [2023] Tyrosine kinase inhibitors have been successfully developed in combination with immune checkpoint inhibitors to treat advanced renal cell carcinoma (RCC), further advancing treatment. While safety profiles are generally manageable with combination regimens, overlapping adverse events (AEs) and immune-related AEs can make treatment more complex. The CheckMate 9ER study evaluated the tyrosine kinase inhibitor cabozantinib in combination with the anti-programmed cell death protein-1 antibody nivolumab in patients with previously untreated advanced RCC. Cabozantinib + nivolumab demonstrated superiority over sunitinib for progression-free survival, overall survival, and objective response rate. These outcomes supported the approval of cabozantinib + nivolumab as a first-line therapy for advanced RCC. The safety profile was manageable with prophylaxis, supportive care, dose holds and reductions for cabozantinib, and dose holds and immunosuppressive therapy for nivolumab. This review discusses the safety results of CheckMate 9ER and provides guidance on managing some of the more clinically relevant AEs with a focus on overlapping AEs, including diarrhea, elevated amylase/lipase, hepatotoxicity, dermatologic reactions, fatigue, endocrine disorders, and nephrotoxicity. We discuss AE management strategies (prophylaxis, supportive care, dose modification, and immunosuppressive therapy), and provide recommendations for identifying the causative agent of overlapping AEs and for consulting specialists about organ-specific immune-related AEs. Optimizing AE management can maintain tolerability and should be a priority with cabozantinib + nivolumab treatment.

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] Introduction: The combination of immunotherapy and targeted therapy is currently marking a new era in the treatment of renal cancer. The latest clinical guidelines recommend the use of drug combinations for the first-line treatment of advanced renal cancer. The aim of this review is to compare the efficacy of combined cabozantinib + nivolumab therapy with other immune checkpoint inhibitors combined with tyrosine kinase inhibitors or monoclonal antibodies blocking the CTLA-4 (cytotoxic T cell antigen 4) in the first-line treatment of metastatic clear-cell renal cell carcinoma (RCC). Methodology: A systematic literature search was carried out in the PubMed and EMBASE databases. Randomized controlled trials (RCTs) on therapies recommended by the latest EAU and ESMO guidelines for treatment-naïve metastatic RCC (i.e., lenvatinib + pembrolizumab, axitinib + pembrolizumab and nivolumab + ipilimumab) were searched. A network meta-analysis (NMA) was performed for data synthesis. The methodology of included RCTs was assessed using the Cochrane RoB two tool. The data were analyzed in the overall population as well as in risk subgroups defined according to the International Metastatic Database Consortium (IMDC) i.e., patients with a favorable and intermediate or poor prognoses. The most recent cut-off dates from included studies were analyzed. Results: Four RCTs (CheckMate 9 ER, KEYNOTE-426, CLEAR and CheckMate 214) were included in the review. No studies directly comparing cabozantinib + nivolumab with any of the drug combinations included in this review were available. NMA showed that cabozantinib + nivolumab was superior compared to axitinib + pembrolizumab and nivolumab + ipilimumab in all analyzed comparisons (overall population and IMDC risk subgroups), both in terms of overall survival and progression-free survival (PFS). The advantage of cabozantinib + nivolumab was statistically significant only for PFS when compared to nivolumab + ipilimumab in the overall population. The results for the comparison of cabozantinib + nivolumab with lenvatinib + pembrolizumab showed numerical superiority of lenvatinib + pembrolizumab combination in terms of overall survival, but none of the results were statistically significant. The advantage of lenvatinib + pembrolizumab over cabozantinib + nivolumab in terms of PFS was statistically significant in the overall and favorable prognosis population. Conclusion: Inclusion of the most recent cut-off data from CheckMate 9 ER did not affect the role of the cabozantinib + nivolumab combination for treatment-naïve metastatic RCC. Cabozantinib + nivolumab is an effective therapeutic option for the first-line treatment of advanced renal cancer that is recommended both in the latest European and American guidelines for all IMDC risk groups.