Cabozantinib + Nivolumab for Kidney Cancer
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: University of Texas Southwestern Medical Center
Must be taking: Cabozantinib
Must not be taking: Warfarin, Dabigatran, Clopidogrel
Disqualifiers: Brain metastases, Uncontrolled hypertension, others
No Placebo Group
Prior Safety Data
Breakthrough Therapy
Trial Summary
What is the purpose of this trial?This trial is testing higher doses of cabozantinib or a combination of cabozantinib with nivolumab in patients with advanced kidney cancer who did not respond to previous treatment. Cabozantinib stops cancer growth, while nivolumab helps the immune system fight the cancer. Cabozantinib and nivolumab have been used together to treat advanced renal cell carcinoma, showing benefits in disease control and survival.
Will I have to stop taking my current medications?
The trial does not specify if you need to stop taking your current medications, but there is no washout period required for cabozantinib. For other cancer treatments, a washout period of 4 weeks or 4 half-lives, whichever is shorter, is needed. Some anticoagulants are not allowed, so check with the trial team about your specific medications.
What data supports the effectiveness of the drug combination Cabozantinib and Nivolumab for kidney cancer?
The combination of Cabozantinib and Nivolumab has been shown to be effective as a first-line treatment for advanced renal cell carcinoma (RCC), with studies indicating longer progression-free survival and improved overall survival compared to the drug Sunitinib. Patients also reported better quality of life with this combination.
12345Is the combination of Cabozantinib and Nivolumab safe for treating kidney cancer?
The combination of Cabozantinib and Nivolumab has been studied for safety in treating advanced kidney cancer. While the safety profile is generally manageable, some side effects like diarrhea, liver issues, skin reactions, fatigue, and kidney problems can occur. These side effects can often be managed with supportive care and dose adjustments.
12467How is the drug combination of Cabozantinib and Nivolumab unique for treating advanced kidney cancer?
The combination of Cabozantinib and Nivolumab is unique because it pairs a tyrosine kinase inhibitor (Cabozantinib) with an immune checkpoint inhibitor (Nivolumab), offering improved progression-free survival and overall survival compared to traditional treatments like sunitinib. This combination is recommended as a first-line treatment for advanced renal cell carcinoma in both European and American guidelines.
12458Eligibility Criteria
Adults with advanced kidney cancer who've seen their disease progress after cabozantinib treatment can join. They must have used cabozantinib for over 6 months, be able to take it without severe side effects, and not be on certain medications or have specific health conditions. Participants need measurable cancer growth, good organ function, and a performance status indicating they can walk and care for themselves.Inclusion Criteria
I can take care of myself but might not be able to do heavy physical work.
My advanced kidney cancer responded to cabozantinib treatment for over 6 months.
Capable of understanding and complying with the protocol requirements and must have signed the informed consent document
+9 more
Exclusion Criteria
I don't have another cancer needing treatment right now, except for certain exceptions.
I haven't had radiation for bone metastasis in the last 2 weeks or any radiation in the last 4 weeks.
My brain metastases are treated and have been stable.
+15 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive cabozantinib 80mg PO daily for dose escalation after progression on cabozantinib monotherapy
Up to 24 months
Follow-up
Participants are monitored for safety and effectiveness after treatment
Up to 36 months
Participant Groups
The trial is testing two approaches in patients whose kidney cancer has worsened despite previous treatment: one group will receive a high dose of cabozantinib alone, while the other will get a lower dose combined with nivolumab. The choice between these options depends on what dosage participants tolerated before.
1Treatment groups
Experimental Treatment
Group I: Cabozantinib Dose EscalationExperimental Treatment1 Intervention
cabozantinib 80mg PO daily
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 NearbySelect from list below to view details:
UT Southwestern Medical CenterDallas, TX
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Who Is Running the Clinical Trial?
University of Texas Southwestern Medical CenterLead Sponsor
ExelixisIndustry Sponsor
References
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).
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.
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.
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.
Cabozantinib plus Nivolumab: A Review in Advanced Renal Cell Carcinoma. [2022]Dual therapy with a tyrosine kinase inhibitor (TKI) and either a programmed death protein/ligand 1 (PD-1/PD-L1) or cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitor has proven efficacy as treatment for previously-untreated advanced renal cell carcinoma (RCC). The combination of the multi-targeted TKI cabozantinib (Cabometyx®) and the anti-PD-1 monoclonal antibody nivolumab (Opdivo®) is approved as first line treatment for RCC in the EU, USA and multiple other countries. In the CheckMate 9ER trial, combination therapy with cabozantinib and nivolumab was superior to sunitinib monotherapy as first line treatment for advanced RCC, demonstrating significantly longer progression-free survival and, importantly, improved overall survival. Patients receiving the combination were also more likely to respond than those treated with sunitinib monotherapy. In addition, health-related quality of life was significantly better with cabozantinib plus nivolumab at nearly all time points during the study. The tolerability profile of the combination was consistent with that seen in previous studies evaluating the two drugs as monotherapy, although more patients who received the combination had serious adverse events than those treated with sunitinib monotherapy. In summary, cabozantinib plus nivolumab is a recommended option for first-line treatment of previously-untreated advanced RCC.
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.
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.
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.