Surgery + Immunotherapy + Targeted Therapy for Kidney Cancer

(Cyto-KIK Trial)

Recruiting in Palo Alto (17 mi)

+3 other locations

Overseen by Mark N Stein, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Mark Stein

Must not be taking: Anticoagulants, Corticosteroids, Immunosuppressives, others

Disqualifiers: Nephrectomy, Hypertension, Autoimmune disease, others

No Placebo Group

Prior Safety Data

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

The purpose of this study is to determine if the use of immunotherapy nivolumab and the targeted therapy cabozantinib prior to removal of the kidney, will increase the number subjects who are without any visible kidney cancer in their body at some point during the course of treatment.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are on certain blood thinners or medications that suppress the immune system, you may need to adjust or stop them. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the drug combination of cabozantinib and nivolumab for kidney cancer?

Research shows that the combination of cabozantinib and nivolumab improved progression-free survival (the time during and after treatment that a patient lives with the disease without it getting worse) and overall survival in patients with advanced kidney cancer compared to another drug, sunitinib. ^{1 2 3 4 5}

Is the combination of cabozantinib and nivolumab safe for kidney cancer treatment?

The combination of cabozantinib and nivolumab has been studied for advanced kidney cancer, and while it has a manageable safety profile, it can cause side effects like diarrhea, liver issues, skin reactions, fatigue, and kidney problems. These side effects can often be managed with supportive care and dose adjustments. ^{1 2 6 7 8}

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

The combination of Cabozantinib and Nivolumab is unique because it pairs a multi-targeted tyrosine kinase inhibitor (Cabozantinib) with an immune checkpoint inhibitor (Nivolumab), which has shown to improve survival and quality of life in advanced kidney cancer compared to traditional treatments like sunitinib. ^{1 2 3 4 9}

Eligibility Criteria

Adults with kidney cancer that has spread, who haven't had treatment for metastatic renal cell carcinoma. They must be in good physical condition (ECOG 0-1), have a measurable tumor, and agree to use two forms of contraception if of childbearing potential. Excluded are those with recent significant bleeding or radiation therapy, active or progressive other cancers, certain heart conditions, uncontrolled hypertension, brain metastases, major surgery within the last 8 weeks, systemic infections within the last month or on immunosuppressants.

Inclusion Criteria

Females of childbearing potential and males must be willing to abstain from heterosexual activity or to use 2 forms of effective methods of contraception from the time of informed consent until 6 months after treatment discontinuation. The two contraception methods can be comprised of two barrier methods, or a barrier method plus a hormonal method

I am not pregnant and can prove it with a test, or I cannot have children due to surgery or menopause.

I am 18 years old or older.

Exclusion Criteria

I haven't had a severe infection needing treatment in the last 28 days.

I haven't had any serious wounds, ulcers, or bone fractures that haven't healed in the last 28 days.

I have been treated with PD-1/PD-L1 or anti-CTLA-4 inhibitors before.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive cabozantinib and nivolumab for approximately 12 weeks prior to nephrectomy

12 weeks

Nivolumab administered every 4 weeks, cabozantinib daily

Surgery

Participants undergo cytoreductive nephrectomy to remove the kidney tumor

1 week

1 surgical visit

Post-Surgery Treatment

Participants may resume cabozantinib and nivolumab if benefiting from treatment

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 5 years

Treatment Details

Interventions

• Cabozantinib (Kinase Inhibitor)
• Cytoreductive Nephrectomy (Surgery)
• Nivolumab (Checkpoint Inhibitor)

Trial Overview The trial is testing whether combining nivolumab (an immunotherapy drug) and cabozantinib (a targeted therapy) before surgically removing the kidney can clear visible signs of kidney cancer more effectively than current treatments. Participants will receive these drugs prior to undergoing cytoreductive nephrectomy.

Participant Groups

Group I: Treatment with cabozantinib and nivolumab with nephrectomy Experimental Treatment 3 Interventions

All study participants will receive the same study medications, cabozantinib and nivolumab. The study drug, nivolumab, will be administered through an IV infusion every 4 weeks and cabozantinib will be administered orally daily. Initially participants will receive study treatment for 12 weeks. The cabozantinib will then be stopped prior to the nephrectomy. Initially patients enrolled on the study will be assigned to cohort 1. Patients who are assigned to cohort 1 will be treated with cabozantinib until 21 days prior to surgery. A patient in cohort 1 will be evaluable for assessment of the cabozantinib washout interval ("evaluable patients") if they 1. complete at least 10 of the 14 scheduled cabozantinib doses in the two week period prior to stopping cabozantinib AND 2. have surgical resection of the primary tumor. In cohort 2, subjects will receive cabozantinib until 14 days prior to nephrectomy.

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:

Columbia University Irving Medical Center New York, NY

The Rutgers Cancer Institute of New Jersey New Brunswick, NJ

Cleveland Clinic Cleveland, OH

Ohio State University Wexner Medical Center Columbus, OH

Who Is Running the Clinical Trial?

Mark Stein Lead Sponsor

Bristol-Myers Squibb Industry Sponsor

Exelixis Industry Sponsor

References

1. 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).

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. Switzerland pubmed.ncbi.nlm.nih.gov

Neoadjuvant nivolumab and cabozantinib in advanced renal cell carcinoma in a horseshoe kidney - how to achieve a safe and radical resection? a case report and review of the literature. [2023] Neoadjuvant nivolumab and cabozantinib in locally advanced renal cell carcinoma in a horseshoe kidney is a novel therapeutic approach in the preoperative setting.

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

Cost-Effectiveness Analysis of First-Line Nivolumab Plus Cabozantinib for Advanced Renal Cell Carcinoma in the United States. [2021] Nivolumab plus cabozantinib improved progression-free survival and overall survival compared with sunitinib in the first-line treatment of advanced renal cell carcinoma (RCC) according to CheckMate 9ER study.

5. 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.

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. 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.

8. 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.

9. France pubmed.ncbi.nlm.nih.gov

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.