What side effects are associated with this type of intervention?

The combination of Cabozantinib, Nivolumab, and Ipilimumab for the treatment of advanced Renal Cell Carcinoma can lead to a range of side effects. Common side effects of Cabozantinib include hypertension, diarrhea, fatigue, and hand-foot syndrome. Nivolumab and Ipilimumab, as immune checkpoint inhibitors, can cause immune-related adverse events such as skin reactions, endocrine disorders, and gastrointestinal issues like colitis. When used in combination, these treatments can result in serious adverse reactions, including pneumonia, diarrhea, febrile neutropenia, anemia, acute kidney injury, and respiratory failure. It is important for patients to discuss these potential side effects with their healthcare provider to manage and mitigate risks effectively.

What prior FDA approvals exist?

The FDA has approved several treatments for Renal Cell Carcinoma (RCC) that involve tyrosine kinase inhibitors and immune checkpoint inhibitors. Cabozantinib, a tyrosine kinase inhibitor, is approved for advanced RCC. Nivolumab, a PD-1 checkpoint inhibitor, is approved for RCC, often in combination with ipilimumab, a CTLA-4 checkpoint inhibitor, for first-line treatment of intermediate or poor-risk advanced RCC. Additionally, combinations like avelumab plus axitinib and pembrolizumab plus axitinib have also received FDA approval for advanced RCC, highlighting the effectiveness of combining tyrosine kinase inhibitors with immune checkpoint inhibitors.

What other types of research exist?

Promising novel alternatives for RCC patients include: <ol> <li>Avelumab plus Axitinib: This combination has shown efficacy in the JAVELIN Renal 101 trial.</li> <li></li> </ol> Pembrolizumab plus Axitinib: Demonstrated positive outcomes in the KEYNOTE-426 study. 3. Atezolizumab plus Bevacizumab: Effective in the IMmotion151 trial. 4. Lenvatinib plus Pembrolizumab: Shown to be effective in the CLEAR study. 5. Enfortumab Vedotin: Emerging as a potential treatment in urothelial carcinoma, which may extend to RCC.

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Tyrosine Kinase Inhibitor

Cabozantinib + Nivolumab + Ipilimumab for Kidney Cancer

Phase 2

Recruiting

Led By Bradley McGregor, MD

Research Sponsored by Bradley A. McGregor, MD

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Age ≥ 18 years

ECOG performance status ≤1

Must not have

Bleeding diathesis, or significant coagulopathy in the absence of therapeutic anticoagulation

Prior allogenic stem cell or solid organ transplant

Timeline

Screening 3 weeks

Treatment Varies

Follow Up defined as the percentage of patients with partial (pr) or complete response (cr) as best overall response according to recist 1.1 by investigator assessment up to 21 months

Awards & highlights

No Placebo-Only Group

Summary

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.

Who is the study for?

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.

What is being tested?

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.

What are the potential side effects?

Possible side effects include liver problems, diarrhea, fatigue, skin rash and itching. There may also be risks of immune-related issues like inflammation in organs such as lungs or intestines and potential hormonal gland problems.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I am 18 years old or older.

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I am fully active and can carry on all pre-disease activities without restriction.

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My kidney cancer cannot be removed by surgery and has spread.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have a bleeding disorder not caused by blood thinners.

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

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I am not taking any strong drugs that affect liver enzymes.

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I cannot receive medications through an IV.

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I have a history of specific lung conditions or signs of lung inflammation on a recent chest CT.

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I have been treated with cabozantinib before.

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I have been treated with CD137 agonists and immune checkpoint inhibitors before.

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I have a history of certain infectious diseases.

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I have a condition that prevents my body from absorbing nutrients properly.

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I have serious heart problems.

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I haven't taken any immunosuppressive drugs in the last 2 weeks.

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I cannot swallow pills.

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I have a serious stomach or intestine condition that could lead to bleeding or a tear.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ defined as the percentage of patients with partial (pr) or complete response (cr) as best overall response according to recist 1.1 by investigator assessment up to 21 months

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~defined as the percentage of patients with partial (pr) or complete response (cr) as best overall response according to recist 1.1 by investigator assessment up to 21 months

This trial's timeline: 3 weeks for screening, Varies for treatment, and defined as the percentage of patients with partial (pr) or complete response (cr) as best overall response according to recist 1.1 by investigator assessment up to 21 months for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Overall Response Rate

Secondary study objectives

"Number of Participants with TreatmentRelated Adverse Events as Assessed by CTCAE version 5.

Duration of response (DOR)

Objective response rate (ORR)

+4 more

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

1Treatment groups

Experimental Treatment

Group I: CabozantinibExperimental Treatment3 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)

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Cabozantinib

2020

Completed Phase 2

~2360

Ipilimumab

2015

Completed Phase 3

~3420

Nivolumab

2015

Completed Phase 3

~4010

0 / 16Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The most common treatments for Renal Cell Carcinoma (RCC) include Tyrosine Kinase Inhibitors (TKIs) and Immune Checkpoint Inhibitors (ICIs). TKIs, like Cabozantinib, inhibit enzymes that promote cancer cell growth and angiogenesis, thereby slowing tumor progression. ICIs, such as Nivolumab and Ipilimumab, enhance the immune system's ability to target and destroy cancer cells by blocking inhibitory proteins on immune cells. This dual approach is significant for RCC patients as it combines direct inhibition of tumor growth with an enhanced immune response, offering a comprehensive strategy to manage advanced or metastatic RCC.

Results of a multicenter, phase 2 study of nivolumab and ipilimumab for patients with advanced rare genitourinary malignancies.Immunotherapy in kidney cancer: the past, present, and future.Nivolumab for the treatment of cancer.