69 Participants Needed

Zanzalintinib + Nivolumab for Kidney Cancer

(EXPLORE-RCC Trial)

QQ
AL
Overseen ByAhran Lee
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
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 trial explores a new combination of treatments for kidney cancer that is difficult to remove surgically. Participants will receive two medications: zanzalintinib, a potential new drug, and nivolumab, an immunotherapy. The aim is to determine if these medications help shrink the tumor or keep it stable. After 12 weeks, doctors will assess whether surgery is an option or if continued medication is the best course. Eligible participants have kidney cancer that cannot be surgically removed and have not received certain treatments for this cancer before. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial requires stopping certain medications, such as oral anticoagulants and complementary medicines, before starting the study treatment. If you're on these, you may need to stop them a few days before the trial begins. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that the combination of zanzalintinib and nivolumab has been tested in patients with advanced kidney cancer. The treatment proved effective for many, with 63% of patients experiencing tumor shrinkage and 90% seeing either shrinkage or no growth. It is generally considered safe for patients.

While all medications can have side effects, studies suggest that these are manageable for most people. Several studies have tested the combination without major safety concerns, indicating a good level of safety for potential trial participants.12345

Why do researchers think this study treatment might be promising for kidney cancer?

Unlike the standard treatments for kidney cancer, which often include drugs like sunitinib or pazopanib, the combination of Zanzalintinib and Nivolumab represents a novel approach. Researchers are excited about this treatment because Zanzalintinib (XL092) is an innovative tyrosine kinase inhibitor that targets multiple pathways involved in tumor growth and spread. When paired with Nivolumab, an immune checkpoint inhibitor that helps the immune system recognize and attack cancer cells, the combination could enhance the body's ability to fight the cancer more effectively. This dual-action strategy has the potential to improve outcomes for patients who may not respond well to traditional therapies.

What evidence suggests that this treatment might be an effective treatment for kidney cancer?

Research shows that the combination of zanzalintinib and nivolumab, which participants in this trial will receive, may be promising for treating kidney cancer. Studies found that 63% of patients experienced tumor shrinkage, indicating the treatment's effectiveness for many. Additionally, the treatment prevented cancer growth in 90% of patients. On average, patients lived 18.5 months without their cancer worsening. These findings suggest that zanzalintinib and nivolumab could effectively manage advanced kidney cancer.12367

Who Is on the Research Team?

QQ

Qian Qin, MD

Principal Investigator

University of Texas

Are You a Good Fit for This Trial?

This trial is for adults with advanced kidney cancer that can't be removed by surgery or has spread a little. They should be fairly active (able to care for themselves), have recovered from past treatments, and their blood counts need to meet certain levels. People with very small metastases are allowed. Those who've given consent and have confirmed clear cell renal carcinoma diagnosis can join.

Inclusion Criteria

I have signed the consent form and agreed to share my health information.
My white blood cell count is healthy without needing medication in the last 2 weeks.
My hemoglobin level is 9 g/dL or higher without recent transfusions.
See 6 more

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive zanzalintinib 100mg orally once daily plus nivolumab standard of care dosing for a total of 12 weeks

12 weeks
Bi-weekly or monthly visits for nivolumab administration

Restaging and Evaluation

Participants undergo restaging scan/evaluation for surgical operability

1-2 weeks

Adaptive Treatment

Participants receive up to 48 weeks total of zanzalintinib plus nivolumab if partial response or stable disease but inoperable, or stop treatment for standard care if disease progression

Up to 48 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

48 weeks

What Are the Treatments Tested in This Trial?

Interventions

  • Nivolumab
  • Zanzalintinib
Trial Overview Patients will take Zanzalintinib pills daily and get Nivolumab injections every 2-4 weeks for 12 weeks. Afterward, they might get surgery if possible, continue treatment if the disease hasn't worsened but isn't operable, or switch to standard care if the cancer grows.
How Is the Trial Designed?
1Treatment groups
Experimental Treatment
Group I: Zanzalintinib (XL092) and NivolumabExperimental Treatment2 Interventions

Find a Clinic Near You

Who Is Running the Clinical Trial?

Qian Qin

Lead Sponsor

Trials
2
Recruited
130+

Exelixis

Industry 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

University of Texas

Collaborator

Trials
193
Recruited
143,000+

Citations

Press Release - Exelixis, Inc.Zanzalintinib in combination with nivolumab demonstrated an objective response rate of 63% and a disease control rate of 90%.
2.pubmed.ncbi.nlm.nih.govpubmed.ncbi.nlm.nih.gov/40008409/
a phase III study of zanzalintinib (XL092) plus nivolumab in ...STELLAR-304 is a phase III trial evaluating first-line zanzalintinib plus nivolumab versus sunitinib in advanced nccRCC.
Zanzalintinib (zanza) + nivolumab (nivo) ± relatlimab (rela) ...Results: In the zanza + nivo arm (n = 40), 75% had intermediate or poor IMDC risk disease. After median follow-up of 16.1 months, the ORR was 63 ...
Zanzalintinib plus nivolumab shows safety, efficacy for ...Zanzalintinib and nivolumab showed a 63% response rate and 18.5-month median PFS in stage 4 RCC. · The study included patients with advanced RCC, ...
STELLAR-304: a phase III study of zanzalintinib (XL092) ...Safety and efficacy of nivolumab in patients with advanced non-clear cell renal cell carcinoma: results from the phase IIIb/iv CheckMate 374 study. Clin ...
STELLAR-304: a phase III study of zanzalintinib (XL092) plus ...In a phase Ib study in advanced solid tumors, cabozantinib plus atezolizumab (a PD-L1 inhibitor) led to an ORR of 31% (80% CI: 20–44) and median PFS of 9.5 (95% ...
ESMO 2025: EXPLORE-RCC: A Phase II Study of ...This study was powered to detect an improvement in objective response rate (ORR) to 0.45 compared with a historical control rate of 0.3, with 80 ...
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