855 Participants Needed

Cabozantinib + Immunotherapy for Kidney Cancer

(COSMIC-313 Trial)

Recruiting at 166 trial locations
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Pivotal Trial (Near Approval)This treatment is in the last trial phase before FDA approval
Prior Safety DataThis treatment has passed at least one previous human trial
Breakthrough TherapyThis drug has been fast-tracked for approval by the FDA given its high promise

What You Need to Know Before You Apply

What is the purpose of this trial?

This is a multicenter, randomized, double-blinded, controlled Phase 3 trial of cabozantinib in combination with nivolumab and ipilimumab versus nivolumab and ipilimumab in combination with matched placebo. Approximately 840 eligible subjects with intermediate- or poor-risk advanced or metastatic RCC by IMDC criteria will be randomized in a 1:1 ratio at approximately 180 sites.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are on certain treatments like systemic anticancer therapy, oral anticoagulants, or immunosuppressive medications. It's best to discuss your specific medications with the trial team.

Is 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. Managing these side effects with supportive care and dose adjustments is important to maintain treatment tolerability.12345

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

This drug combination is unique because it combines a targeted therapy (Cabozantinib) with two immunotherapies (Nivolumab and Ipilimumab), aiming to enhance the immune system's ability to fight kidney cancer while also targeting cancer cell growth. It is recommended for first-line treatment of advanced renal cancer and has shown effectiveness in improving progression-free survival compared to some other drug combinations.12456

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

Research shows that the combination of Cabozantinib and Nivolumab is effective for treating advanced kidney cancer, as it was found to be better than some other drug combinations in terms of survival and slowing disease progression. This combination is recommended in the latest treatment guidelines for advanced kidney cancer.12567

Are You a Good Fit for This Trial?

This trial is for adults with advanced or metastatic kidney cancer that hasn't been treated before. They should have a certain level of fitness (KPS ≥ 70%) and measurable disease. People can't join if they've had recent surgeries, live vaccines, other cancers within 3 years, autoimmune diseases needing treatment in the last two years, or are on high-dose steroids.

Inclusion Criteria

My kidney cancer cannot be cured with surgery or radiation and has spread.
My cancer can be measured and is not in an area treated by radiation.
My organs and bone marrow are working well.
See 2 more

Exclusion Criteria

My brain metastases have been treated and stable for at least 4 weeks.
I have had treatment for advanced kidney cancer that couldn't be surgically removed.
I do not have any active infections needing treatment, including hepatitis, HIV/AIDS, or tuberculosis.
See 9 more

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive cabozantinib in combination with nivolumab and ipilimumab or nivolumab and ipilimumab with placebo

16 weeks
4 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

What Are the Treatments Tested in This Trial?

Interventions

  • Cabozantinib
  • Ipilimumab
  • Nivolumab
Trial Overview The study tests Cabozantinib combined with Nivolumab and Ipilimumab against a placebo plus Nivolumab and Ipilimumab in patients with kidney cancer. It's randomized and double-blinded, meaning neither doctors nor patients know who gets the real drug versus placebo.
How Is the Trial Designed?
2Treatment groups
Experimental Treatment
Active Control
Group I: Experimental ArmExperimental Treatment3 Interventions
Cabozantinib + nivolumab + ipilimumab (4 doses) followed by cabozantinib + nivolumab
Group II: Control ArmActive Control3 Interventions
Cabozantinib-matched placebo + nivolumab + ipilimumab (4 doses) followed by cabozantinib-matched placebo + nivolumab

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

Who Is Running the Clinical Trial?

Exelixis

Lead Sponsor

Trials
126
Recruited
20,500+
Michael M. Morrissey profile image

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 profile image

Vicki L. Goodman

Exelixis

Chief Medical Officer since 2022

MD

Published Research Related to This Trial

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.
Cabozantinib plus Nivolumab and Ipilimumab in Renal-Cell Carcinoma.Choueiri, TK., Powles, T., Albiges, L., et al.[2023]
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.
Adverse Events of Cabozantinib Plus Nivolumab Versus Ipilimumab Plus Nivolumab.Blas, L., Shiota, M., Tsukahara, S., 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.
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]

Citations

Cabozantinib plus Nivolumab and Ipilimumab in Renal-Cell Carcinoma. [2023]
Adverse Events of Cabozantinib Plus Nivolumab Versus Ipilimumab Plus Nivolumab. [2023]
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]
Phase II Trial of Cabozantinib Plus Nivolumab in Patients With Non-Clear-Cell Renal Cell Carcinoma and Genomic Correlates. [2023]
Complete response of metastatic papillary renal cell carcinoma with inferior vena cava tumor thrombus to nivolumab plus cabozantinib. [2023]
Management of adverse events associated with cabozantinib plus nivolumab in renal cell carcinoma: A review. [2023]
Nivolumab plus Cabozantinib versus Sunitinib for Advanced Renal-Cell Carcinoma. [2022]
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