XL092 + Nivolumab for Kidney Cancer

(EXACT Trial)

Overseen By Gabrielle Tiggs

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Karie Runcie

Must be taking: Anti-PD-1/L1

Must not be taking: Complementary medications, Corticosteroids

Disqualifiers: Brain metastases, Active infection, Autoimmune disease, others

Stay on Your Current Meds You can continue your current medications while participating

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 92

Duration: Variable (until progression or other criteria)

70 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, there is a required 2-week washout period for those who have progressed on adjuvant anti-PD-1 therapy before starting the study treatment.

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

Research shows that Nivolumab, one of the drugs in the combination, has been effective in treating advanced kidney cancer, improving survival in patients who have already received other treatments. ^{1 2 3 4 5}

Is the combination of XL092 and Nivolumab safe for humans?

Nivolumab, used for kidney cancer, generally has a manageable safety profile, though it can cause side effects like tubulointerstitial nephritis (a kidney condition). In patients with severe kidney issues, nivolumab did not show increased toxicity, suggesting it is similarly safe for those with or without kidney problems. ^{1 6 7 8 9}

What makes the drug XL092 + Nivolumab unique for kidney cancer?

The combination of XL092 and Nivolumab is unique because it pairs a new investigational drug, XL092, with Nivolumab, an established immune checkpoint inhibitor that helps the immune system attack cancer cells. This combination aims to enhance the effectiveness of treatment by targeting different pathways involved in kidney cancer growth and immune evasion. ^{1 2 9 10 11}

What is the purpose of this trial?

The study population for this Phase 2 study will include men and women ≥ 18 with confirmed renal cell carcinoma who have progressed on adjuvant anti-PD-1/PD-L1 therapy, the current standard of care. Subjects will be randomized to Arm A or Arm B. Study treatment will be given in 28-day (4 week) cycles. Arm A treatment will consist of XL092 alone and will be taken once daily continuously (Day 1-Day 28). Arm B treatment will consist of XL092 plus nivolumab. XL092 will be taken once daily continuously (Day 1-Day 28) and nivolumab will be administered every 4 weeks (Day 1). Treatment will continue until progression by RECIST 1.1, toxicity, or other reasons as appropriate.

Research Team

Karie Runcie, MD

Principal Investigator

Columbia University

Eligibility Criteria

Adults over 18 with renal cell carcinoma (a type of kidney cancer) who've seen their cancer progress after standard anti-PD-1/PD-L1 therapy can join. They must have measurable disease, good performance status (able to carry out daily activities), and adequate organ function. Those with unresolved severe side effects from previous treatments or insufficient blood counts are excluded.

Inclusion Criteria

My kidney cancer has spread and shows clear cell features.

Written informed consent and HIPAA authorization for release of personal health information prior to registration. NOTE: HIPAA authorization may be included in the informed consent or obtained separately.

I have been mostly active and able to carry out all my pre-disease activities up to a month ago.

Exclusion Criteria

I have had an organ or stem cell transplant from a donor.

I cannot swallow pills.

I do not have serious GI disorders that could lead to holes or abnormal connections.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive XL092 alone or in combination with nivolumab in 28-day cycles until progression, toxicity, or other reasons

Variable (until progression or other criteria)

XL092 daily, nivolumab every 4 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

Treatment Details

Interventions

• Nivolumab
• XL092

Trial Overview This Phase 2 trial tests XL092 alone or combined with nivolumab in patients whose kidney cancer has worsened despite prior treatment. Participants will be randomly assigned to one of two groups and receive treatment in cycles lasting four weeks until the disease progresses, they experience unacceptable toxicity, or for other reasons.

Participant Groups

Group I: Arm B: XL092 and Nivolumab Experimental Treatment 2 Interventions

Study treatment will be given in 28-day (4 week) cycles. Arm B treatment will consist of XL092 100 mg plus nivolumab 480 mg intravenously. XL092 will be taken once daily continuously (Day 1-Day 28) and nivolumab will be administered every 4 weeks (Day 1). Treatment will continue until progression by RECIST 1.1, toxicity, or other reasons as appropriate.

Group II: Arm A: XL092 Experimental Treatment 1 Intervention

Study treatment will be given in 28-day (4 week) cycles. Arm A treatment will consist of XL092 100 mg orally alone and will be taken once daily continuously (Day 1-Day 28). Treatment will continue until progression by RECIST 1.1, toxicity, or other reasons as appropriate.

Who Is Running the Clinical Trial?

Karie Runcie

Lead Sponsor

Trials

1

Recruited

70+

Exelixis

Industry 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

Columbia University

Collaborator

Trials

1,529

Recruited

2,832,000+

Findings from Research

In a study of 389 patients with metastatic renal cell cancer (mRCC) treated with nivolumab, the treatment showed a 23.1% objective response rate and a median progression-free survival of 4.5 months, indicating its efficacy in this patient population.

The safety profile was favorable, with no treatment-related deaths and only 5.7% of patients discontinuing treatment due to adverse events, suggesting that nivolumab is a safe option for patients, including those who are elderly or have previously received multiple therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of nivolumab for metastatic renal cell carcinoma: real-world results from an expanded access programme. De Giorgi, U., Cartenì, G., Giannarelli, D., et al.[2022]

Nivolumab, when combined with ipilimumab, significantly improves overall survival (OS) and progression-free survival (PFS) in patients with advanced renal cell carcinoma (RCC), based on a meta-analysis of three high-quality randomized controlled trials involving 2550 patients.

The treatment with nivolumab did not lead to an increase in adverse events, indicating a manageable safety profile for patients undergoing this therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Nivolumab for Advanced Renal Cell Carcinoma: A Systematic Review and Meta-Analysis. Zhang, S., Xu, X., Chen, J., et al.[2022]

In a study of 389 metastatic renal cell carcinoma patients with poor prognostic features, nivolumab demonstrated a disease control rate of 53% in those with brain metastasis, 45% in liver metastasis, and 47% in bone metastasis, indicating its efficacy in difficult-to-treat populations.

The safety profile of nivolumab remained consistent with previous studies, with no new safety concerns identified, suggesting it is a safe treatment option for patients with advanced disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Negative prognostic factors and resulting clinical outcome in patients with metastatic renal cell carcinoma included in the Italian nivolumab-expanded access program. Bracarda, S., Galli, L., Maruzzo, M., et al.[2018]

In a study of 91 patients with metastatic renal cell carcinoma (mRCC), nivolumab showed significant improvements in overall survival, with a median survival of 25.2 months for the highest dose (10 mg/kg) and not reached for treatment-naïve patients.

Nivolumab treatment led to substantial increases in tumor-associated lymphocytes and changes in chemokine levels, indicating its immunomodulatory effects, while no new safety concerns were identified.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunomodulatory Activity of Nivolumab in Metastatic Renal Cell Carcinoma. Choueiri, TK., Fishman, MN., Escudier, B., et al.[2022]

Nivolumab, an immune-checkpoint inhibitor used to treat lung adenocarcinoma, can lead to autoimmune side effects, as demonstrated by a case of acute tubulointerstitial nephritis in a 67-year-old patient after three infusions.

The kidney biopsy revealed specific histological changes, including proliferation of certain immune cells, indicating that nivolumab can trigger significant immune responses that may affect organ function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tubulointerstitial nephritis as adverse effect of programmed cell death 1 inhibitor, nivolumab, showed distinct histological findings. Uchida, A., Watanabe, M., Nawata, A., et al.[2021]

Nivolumab, an immune checkpoint inhibitor, appears to be safe for patients with end-stage renal disease (ESRD) and metastatic renal cell carcinoma (mRCC), as none of the three reported cases experienced severe toxicities during treatment.

Among the patients treated with nivolumab, two achieved a partial response, indicating that this therapy can provide clinical benefits for ESRD patients, suggesting that dose adjustments may not be necessary for those on dialysis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outcomes and Safety of Biweekly and Monthly Nivolumab in Patients with Metastatic Renal Cell Carcinoma and Dialysis: Three Case Reports and Literature Review. Osmán-García, I., Congregado-Ruiz, CB., Lendínez-Cano, G., et al.[2021]

A 65-year-old man with advanced renal cell carcinoma achieved a remarkable reduction in metastasis after receiving nivolumab as the fifth systemic therapy, following treatment with angiogenesis inhibitors and interferon-α.

The patient experienced a pathological complete response, with no cancer cells found after adrenalectomy, and remains healthy 20 months post-surgery, highlighting the potential efficacy of nivolumab in advanced renal cell carcinoma cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pathological complete response after nivolumab therapy following angiogenesis inhibitors in a patient with metastatic renal cell carcinoma. Hagimoto, H., Kashima, S., Doi, K., et al.[2022]

Nivolumab, when combined with ipilimumab, significantly improves overall survival rates in previously untreated advanced renal cell carcinoma (RCC), achieving an 18-month survival rate of 75% compared to 60% with sunitinib alone.

The combination therapy also results in a higher objective response rate of 42% versus 27% for sunitinib, indicating that immune checkpoint inhibitors are becoming a promising first-line treatment option for metastatic RCC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Frontline immunotherapy treatment with nivolumab and ipilimumab in metastatic renal cell cancer: a new standard of care. Nizam, A., Aragon-Ching, JB.[2020]

References

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

Safety and efficacy of nivolumab for metastatic renal cell carcinoma: real-world results from an expanded access programme. [2022]

2. Egypt pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Nivolumab for Advanced Renal Cell Carcinoma: A Systematic Review and Meta-Analysis. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Negative prognostic factors and resulting clinical outcome in patients with metastatic renal cell carcinoma included in the Italian nivolumab-expanded access program. [2018]

4. Croatia pubmed.ncbi.nlm.nih.gov

Safety and efficacy of nivolumab as a second line therapy in metastatic renal cell carcinoma: a retrospective chart review. [2020]

5. United States pubmed.ncbi.nlm.nih.gov

Immunomodulatory Activity of Nivolumab in Metastatic Renal Cell Carcinoma. [2022]

6. Japan pubmed.ncbi.nlm.nih.gov

Efficacy and safety profile of nivolumab for Japanese patients with metastatic renal cell cancer. [2020]

7. Japan pubmed.ncbi.nlm.nih.gov

Tubulointerstitial nephritis as adverse effect of programmed cell death 1 inhibitor, nivolumab, showed distinct histological findings. [2021]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Outcomes and Safety of Biweekly and Monthly Nivolumab in Patients with Metastatic Renal Cell Carcinoma and Dialysis: Three Case Reports and Literature Review. [2021]

9. United States pubmed.ncbi.nlm.nih.gov

Safety and Efficacy of Nivolumab in Patients With Advanced Non-Clear Cell Renal Cell Carcinoma: Results From the Phase IIIb/IV CheckMate 374 Study. [2022]

10. Australia pubmed.ncbi.nlm.nih.gov

Pathological complete response after nivolumab therapy following angiogenesis inhibitors in a patient with metastatic renal cell carcinoma. [2022]

11. United States pubmed.ncbi.nlm.nih.gov

Frontline immunotherapy treatment with nivolumab and ipilimumab in metastatic renal cell cancer: a new standard of care. [2020]