XL092 + Nivolumab vs Sunitinib for Kidney Cancer

(STELLAR-304 Trial)

Recruiting at 162 trial locations

Overseen By Backup or International

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Exelixis

Must not be taking: Anticoagulants, Platelet inhibitors

Disqualifiers: Chromophobe, Brain metastases, Major surgery, others

No Placebo Group All 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 Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

Duration: 24 months

291 Participants Needed

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.

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
• Sunitinib Malate
• XL092

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

Who Is Running the Clinical Trial?

Exelixis

Lead Sponsor

Trials

126

Recruited

20,500+

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

Exelixis

Chief Medical Officer since 2022

MD

Findings from Research

Sunitinib is an effective treatment for advanced metastatic renal cell carcinoma (mRCC), showing a significant improvement in progression-free survival compared to interferon-alpha, with 11 months for sunitinib versus 5 months for interferon-alpha in a Phase III study.

In Phase II trials, sunitinib demonstrated a partial response rate of 40% and 34% as a second-line therapy for mRCC patients who did not respond to previous cytokine treatments, indicating its efficacy in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sunitinib (Sutent): a novel agent for the treatment of metastatic renal cell carcinoma. Chouhan, JD., Zamarripa, DE., Lai, PH., et al.[2018]

Sunitinib, a targeted oral medication for advanced renal cell carcinoma (mRCC), significantly improves progression-free survival, achieving a median of 11 months compared to just 5 months with interferon-alpha in a Phase III trial involving previously untreated patients.

The drug is generally well tolerated, with manageable side effects, making it a recommended first-line treatment option for patients with favorable or intermediate prognostic risk in international guidelines.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sunitinib for the management of advanced renal cell carcinoma. Escudier, B.[2020]

Sunitinib has demonstrated superiority as a first-line therapy for intermediate-risk metastatic clear cell renal carcinoma based on three clinical cases.

Bevacizumab combined with interferon showed better safety profiles, highlighting the need for more high-level evidence for neo-adjuvant treatments in kidney cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Case report of kidney cancer from JOUM 2010]. Neuzillet, Y., Guy, L., Long, JA., et al.[2011]

Sunitinib is established as a standard first-line treatment for metastatic clear-cell kidney cancer, demonstrating its efficacy in improving patient outcomes.

The paper reviews overall survival data from a pivotal phase III trial that compared sunitinib to interferon, highlighting its advantages in progression-free survival and response rates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-line therapy with sunitinib in advanced renal cell carcinoma: interpretation of the overall survival data from ASCO 2008. Wood, L.[2021]

Nivolumab (Opdivo®) has been established as an effective second-line treatment for metastatic renal cell carcinoma (mRCC), showing improved overall survival (26 months vs. 19.7 months) and response rates compared to Everolimus, based on the CheckMate 025 trial with 1,080 participants.

The combination of Nivolumab and Ipilimumab has demonstrated a significantly higher objective response rate (42% vs. 27%) and better overall survival in intermediate and high-risk patients compared to Sunitinib, while also improving quality of life, despite an increase in immune-related adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Immunotherapy for renal cell carcinoma - current status]. Grimm, MO., Foller, S.[2019]

Sunitinib has a similar safety profile in patients undergoing nephrectomy for kidney cancer, whether used in the adjuvant setting or for metastatic disease, based on data from phase III trials including CARMENA and SURTIME.

Effective management of sunitinib's adverse effects is crucial, particularly in the adjuvant setting, where maintaining dose intensity and exposure can impact treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of sunitinib in patients with renal cell carcinoma following nephrectomy. Heraudet, L., Domblides, C., Daste, A., et al.[2022]

In a Phase III trial involving treatment-naive patients with metastatic renal cell carcinoma (mRCC), sunitinib significantly improved progression-free survival compared to IFN-α, demonstrating its efficacy as a first-line treatment.

Sunitinib is effective even in challenging cases, such as patients with non-clear cell histology or those who are refractory to other treatments, and while it has common side effects like fatigue and hypertension, these may also indicate better clinical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The use of sunitinib in renal cell carcinoma: where are we now? Czarnecka, AM., Szczylik, C., Rini, B.[2018]

Sunitinib is an effective treatment for metastatic renal cell carcinoma (mRCC) in Japan, showing high therapeutic response and prolonged survival, but it has a distinct toxicity profile that requires careful monitoring.

The most common severe side effect of sunitinib is myelotoxicity, particularly thrombocytopenia, affecting 73% of patients, with 36.8% experiencing grade 3 or higher toxicity, indicating the need for dose adjustments and individualized treatment plans.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Management of sunitinib-associated adverse events]. Kanda, H., Masui, S., Yamada, Y., et al.[2018]

Sunitinib malate is a multi-kinase inhibitor approved for treating advanced renal cell carcinoma and other specific tumors, showing modest antitumor activity in ovarian cancer based on Phase I and II trials.

The drug has an acceptable safety profile, but further research is needed to better understand its toxicity and to explore combination therapies for enhanced efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The potential of sunitinib as a therapy in ovarian cancer. Leone Roberti Maggiore, U., Valenzano Menada, M., Venturini, PL., et al.[2018]

Sunitinib has been established as the standard first-line treatment for advanced renal cell carcinoma, based on results from a large-scale, long-term Phase III trial.

Conventional treatments like nephrectomy followed by IL-2 or IFN-alpha often do not provide long-term survival benefits, highlighting the importance of targeted therapies like sunitinib in improving patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sunitinib (SUTENT) for the treatment of metastatic renal cell carcinoma. Hutson, TE.[2018]

In a study of 41 patients with advanced renal cell carcinoma and renal impairment, both sunitinib and sorafenib showed similar efficacy in terms of progression-free survival (6.6 months for sunitinib vs 5.8 months for sorafenib) and overall survival (65.9 months vs 58.0 months).

However, sunitinib was associated with a higher frequency of grade 3 or higher adverse events compared to sorafenib, indicating a need for careful monitoring of side effects, especially in patients with prior kidney surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sunitinib versus sorafenib for patients with advanced renal cell carcinoma with renal impairment before the immune-oncology therapy era. Takayama, T., Kubo, T., Yamazaki, M., et al.[2020]

References

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

Sunitinib (Sutent): a novel agent for the treatment of metastatic renal cell carcinoma. [2018]

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

Sunitinib for the management of advanced renal cell carcinoma. [2020]

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

[Case report of kidney cancer from JOUM 2010]. [2011]

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]

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

[Immunotherapy for renal cell carcinoma - current status]. [2019]

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

Safety of sunitinib in patients with renal cell carcinoma following nephrectomy. [2022]

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

The use of sunitinib in renal cell carcinoma: where are we now? [2018]

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

[Management of sunitinib-associated adverse events]. [2018]

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

The potential of sunitinib as a therapy in ovarian cancer. [2018]

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

Sunitinib (SUTENT) for the treatment of metastatic renal cell carcinoma. [2018]

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]