XL092 + Nivolumab vs Sunitinib for Kidney Cancer

(STELLAR-304 Trial)

Recruiting in Palo Alto (17 mi)

+162 other locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

Sponsor: Exelixis

Must not be taking: Anticoagulants, Platelet inhibitors

Disqualifiers: Chromophobe, Brain metastases, Major surgery, others

No Placebo Group

Pivotal Trial (Near Approval)

Prior Safety Data

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

This is a multicenter, randomized (2:1), open-label, controlled Phase 3 trial of XL092 in combination with nivolumab versus sunitinib in subjects with unresectable, locally advanced or metastatic nccRCC who have not received prior systemic anticancer therapy.

Will I have to stop taking my current medications?

The trial requires that participants who are taking oral anticoagulants (blood thinners) switch to a different type called LMWH before joining. If you are on platelet inhibitors, you cannot participate. Other medications are not specifically mentioned, so it's best to discuss with the trial team.

What data supports the effectiveness of the drug combination XL092 + Nivolumab for kidney cancer?

Sunitinib, a component of the trial, is a well-established treatment for advanced kidney cancer, showing improved survival rates in multiple studies. Nivolumab, another component, has been shown to improve overall survival and response rates in kidney cancer patients, especially when combined with other immune therapies. ^{1 2 3 4 5}

What is known about the safety of XL092 + Nivolumab vs Sunitinib for kidney cancer?

Sunitinib (Sutent) is generally used for kidney cancer and can cause side effects like fatigue, diarrhea, skin rash, and high blood pressure. It may also lead to more serious issues like low blood cell counts and thyroid problems. Managing these side effects is important for patient comfort and treatment success. ^{1 6 7 8 9}

How is the drug combination XL092 + Nivolumab different from Sunitinib for kidney cancer?

The combination of XL092 and Nivolumab is unique because it combines a new investigational drug (XL092) with an immune checkpoint inhibitor (Nivolumab), potentially offering a novel approach by targeting cancer cells and enhancing the immune system's ability to fight cancer, whereas Sunitinib is a well-established treatment that works by inhibiting multiple protein kinases involved in tumor growth. ^{1 7 9 10 11}

Eligibility Criteria

Adults with advanced or metastatic non-clear cell renal cell carcinoma (nccRCC) that hasn't been treated before can join. They need a certain level of fitness, measurable disease, and proper organ function. Pregnant women, those with specific nccRCC subtypes, recent surgery patients, or individuals who've had certain treatments for this cancer are excluded.

Inclusion Criteria

There is a stored sample of your tumor from a past biopsy.

I am 18 years old or older.

My kidney cancer cannot be surgically removed and has spread.

Exclusion Criteria

I am on blood thinners but can switch to LMWH; I am not on platelet inhibitors.

I have not had major surgery in the last 8 weeks, laparoscopic nephrectomy in the last 4 weeks, or minor surgery in the last 10 days.

Your heart's electrical activity (measured by ECG) shows a prolonged QT interval.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive XL092 + nivolumab or sunitinib for advanced or metastatic nccRCC

24 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

22 months

Treatment Details

Interventions

• Nivolumab (Checkpoint Inhibitor)
• Sunitinib Malate (Tyrosine Kinase Inhibitor)
• XL092 (Other)

Trial Overview The trial is testing XL092 in combination with Nivolumab against Sunitinib alone in people with nccRCC. It's a Phase 3 study where participants are randomly assigned to either the test combo or the standard treatment in a 2:1 ratio without hiding which treatment they receive.

Participant Groups

Group I: XL092 + Nivolumab Experimental Treatment 2 Interventions

Subjects with advanced or metastatic nccRCC will receive XL092 + nivolumab

Group II: Sunitinib Malate Active Control 1 Intervention

Subjects with advanced or metastatic nccRCC will receive an active comparator of sunitinib

Nivolumab is already approved in United States, European Union, Canada, Switzerland for the following indications:

🇺🇸 Approved in United States as Opdivo for:

• Advanced or metastatic gastric cancer
• Gastroesophageal junction cancer
• Esophageal adenocarcinoma
• Melanoma
• Non-small cell lung cancer
• Renal cell carcinoma
• Hodgkin lymphoma
• Head and neck squamous cell carcinoma
• Urothelial carcinoma
• Colorectal cancer
• Hepatocellular carcinoma
• Esophageal squamous cell carcinoma

🇪🇺 Approved in European Union as Opdivo for:

• Melanoma
• Non-small cell lung cancer
• Renal cell carcinoma
• Hodgkin lymphoma
• Head and neck squamous cell carcinoma
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Gastroesophageal junction cancer
• Esophageal adenocarcinoma

🇨🇦 Approved in Canada as Opdivo for:

• Melanoma
• Non-small cell lung cancer
• Renal cell carcinoma
• Hodgkin lymphoma
• Head and neck squamous cell carcinoma
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Gastroesophageal junction cancer
• Esophageal adenocarcinoma

🇨🇭 Approved in Switzerland as Opdivo for:

• Melanoma
• Non-small cell lung cancer
• Renal cell carcinoma
• Hodgkin lymphoma
• Head and neck squamous cell carcinoma
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Gastroesophageal junction cancer
• Esophageal adenocarcinoma

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Exelixis Clinical Site #164 Newport Beach, CA

Exelixis Clinical Site #162 San Francisco, CA

Exelixis Clinical Site #163 Aurora, CO

Exelixis Clinical Site #161 Buffalo, NY

More Trial Locations

Who Is Running the Clinical Trial?

Exelixis Lead Sponsor

References

1. England pubmed.ncbi.nlm.nih.gov

Sunitinib (Sutent): a novel agent for the treatment of metastatic renal cell carcinoma. [2018] To provide a review of the clinical data supporting the use of sunitinib (Sutent), a multitargeted, small molecule, tyrosine kinase inhibitor, with focus on its approved indication for the treatment of advanced renal cell carcinoma in patients with metastatic disease requiring drug therapy.

2. England pubmed.ncbi.nlm.nih.gov

Sunitinib for the management of advanced renal cell carcinoma. [2020] Targeted agents, such as sunitinib (SUTENT((R))) have become central to the management of advanced and/or metastatic renal cell carcinoma (mRCC). Sunitinib is an oral, multitargeted receptor tyrosine kinase inhibitor that has demonstrated efficacy for the treatment of mRCC in multiple clinical trials. In a Phase III trial in previously untreated patients with mRCC, sunitinib was associated with median progression-free survival of 11 months, which was more than double that observed with interferon-alpha (5 months; p

3. France pubmed.ncbi.nlm.nih.gov

[Case report of kidney cancer from JOUM 2010]. [2011] Three clinical cases have shown the superiority of sunitinib in first line therapy intermediate risk metastatic clear cell renal carcinoma and a best safety of bevacizumab plus interferon, the current lack of high level of evidence arguments for the neo-adjuvant treatment of kidney cancer, the importance to prevent mucositis during a mTOR inhibitors treatment and the diagnostic pitfalls of its pulmonary complications.

4. Switzerland pubmed.ncbi.nlm.nih.gov

First-line therapy with sunitinib in advanced renal cell carcinoma: interpretation of the overall survival data from ASCO 2008. [2021] Sunitinib is now a standard first-line therapy for metastatic clear-cell kidney cancer. This paper focuses on interpretation of the overall survival data presented at the 2008 annual meeting of the American Society of Clinical Oncology from the pivotal phase iii trial comparing sunitinib with interferon in the first-line setting. The previously published progression-free survival and response rate data from that study are also summarized.

5. Germany pubmed.ncbi.nlm.nih.gov

[Immunotherapy for renal cell carcinoma - current status]. [2019] Systemic treatment of metastatic renal cell carcinoma (mRCC) has substantially changed during the last 2 years due to approval of the immune-checkpoint inhibitor Nivolumab (Opdivo®) and new multikinase inhibitors (Cabozantinib, Lenvatinib, Tivozanib). The german kidney tumor guideline strongly recommends Nivolumab and Cabozantinib as 2nd line treatments after prior VEGF targeted therapy. CheckMate 025, the prospective randomized trial which led to approval of Nivolumab demonstrated improved overall survival (26 month vs. 19.7 month; hazard ratio 0.73; p = 0.0006) and response rate (26 % vs. 5 %) as well as a favorable toxicity profile compared with Everolimus. Currently, numerous combinations with PD-1/PD-L1 inhibitors are compared to Sunitinib as first line treatment of mRCC. Out of these CheckMate 214, a randomized phase-3 trial is the first to demonstrate a significant higher objective response rate (42 % vs. 27 %, p < 0.0001) and overall survival (Sunitinib 26.0 month, median for Nivo + Ipi has been not yet reached (28.2 - NR); Hazard ratio 0.63) for the combination of Nivolumab and the CTLA-4 antibody Ipilimumab in IMDC intermediate and high risk patients. Furthermore, CheckMate 214 shows better side effect profile and quality of life in patients receiving Nivolumab and Ipilimumab compared with Sunitinib. However, a considerable increase of immune related adverse events is associated with the immune combination therapy. Another randomized trial demonstrates improved progression-free survival for the combination of the PD-L1 inhibitor Atezolizumab and the VEGF antibody Bevacizumab in patients with PD-L1 positive tumors; this was found in all IMDC risk groups. Further phase-3 trials with "new" VEGFR-TKIs (Axitinib, Cabozantinib, Lenvatinib) and PD-1/PD-L1 inhibitor combinations are ongoing.In conclusion, the PD-1 immune checkpoint inhibitor Nivolumab will remain a standard treatment for patients with metastatic renal cell carcinoma after prior VEGF targeted therapy. Nivolumab in combination with Ipilimumab will become a standard 1st line option for patients with intermediate and high risk profile according to IMDC. Further data are required regarding PD-1/PD-L1 inhibitors in combination with Bevacizumab and VEGFR-TKIs, respectively, including overall survival and side effect profile.

6. England pubmed.ncbi.nlm.nih.gov

Safety of sunitinib in patients with renal cell carcinoma following nephrectomy. [2022] The safety profile characteristics of sunitinib were evaluated in patients who underwent nephrectomy for kidney cancer.

7. England pubmed.ncbi.nlm.nih.gov

The use of sunitinib in renal cell carcinoma: where are we now? [2018] Sunitinib malate (Sutent™) is an inhibitor of multiple protein tyrosine kinases that shows antitumor and antiangiogenic activities. In a randomized Phase III trial of treatment-naive patients with metastatic renal cell carcinoma (mRCC), patients treated with sunitinib showed a significant improvement in progression-free survival compared with those treated with IFN-α. Sunitinib also exhibited antitumor activity in unselected RCC patients, including those with who were refractory to treatment, had non-clear cell histology brain metastases, or an Eastern Cooperative Oncology Group performance status >1. Typical side effects of sunitinib malate are fatigue, asthenia, diarrhea, skin rash, stomatitis, hand-foot skin syndrome, hypothyroidism and hematological abnormalities. Hypertension, other toxicities may serve as biomarkers for improved clinical outcomes in sunitinib treatment. Currently, sunitinib remains the gold standard of care in the treatment of mRCC.

8. Japan pubmed.ncbi.nlm.nih.gov

[Management of sunitinib-associated adverse events]. [2018] Patients diagnosed with metastatic renal cell carcinoma (mRCC) are currently treated with oral tyrosine kinase inhibitors (TKIs). Sunitinib malate (Sutent R Pfizer INC) is an oral multitargeted TKI and is the mainstay of therapy for mRCC patients in Japan. Although it shows a high therapeutic response and prolonged survival rates, sunitinib exhibits a novel and distinct toxicity profile that requires appropriate monitoring and management. Therefore, the physician needs to understand the modalities to detect and cope with such adverse events to effectively treat the patient. We summarized the management of the most frequent and clinically significant adverse events of sunitinib treatment. Myelotoxicity, especially thrombocytopenia seemed to be the most common and severe toxicity (73% all grade, 36.8%, ≧grade 3). The incidences of thyroid dysfunction, fatigue, hypertension, hand-foot syndrome, nausea, diarrhea and oral changes were reviewed. The incidences of ≧grade 3 adverse events and dose reduction were higher than those in western reports. In our institution, fever was frequently observed (up to 63.1%). When the patient is at high risk of sunitinib assosicated adverse events, dose reduction from the beginning of sunitinib therapy may be useful. To maintain the patient's quality of life and for long-term administration of the sunitinib, it is worth while to modulate the sunitinib administration schedule for each patient.

9. England pubmed.ncbi.nlm.nih.gov

The potential of sunitinib as a therapy in ovarian cancer. [2018] Sunitinib malate (SU11248; Sutent®; Pfizer, Inc., New York) is a multi-kinase inhibitor currently approved for use in advanced renal cell carcinoma (RCC), imatinib-resistant/-intolerant gastrointestinal stromal tumours and progressive, well-differentiated pancreatic neuroendocrine tumours in patients with unresectable, locally advanced or metastatic disease.

10. England pubmed.ncbi.nlm.nih.gov

Sunitinib (SUTENT) for the treatment of metastatic renal cell carcinoma. [2018] Kidney cancer accounts for approximately 2% of new cancers and conventional treatment with nephrectomy followed by IL-2 or IFN-alpha treatment does not provide long-term survival benefit in many patients. Increased understanding of the pathophysiology of renal cell carcinoma has prompted the development of targeted therapies for patients with this disease, including sunitinib. This paper reviews the most recent efficacy and safety data for sunitinib, as well as currently ongoing and planned studies for this receptor tyrosine kinase inhibitor. Results from a large-scale, long-term, Phase III trial have established sunitinib as the standard of care for first-line treatment of patients with advanced renal cell carcinoma, and it is now the reference standard against which other therapies for this cancer should be evaluated.

11. England pubmed.ncbi.nlm.nih.gov

Sunitinib versus sorafenib for patients with advanced renal cell carcinoma with renal impairment before the immune-oncology therapy era. [2020] The efficacy and safety of sunitinib versus sorafenib in patients with advanced renal cell carcinoma with renal impairment remains poorly documented.