SLM-Axitinib-Pembrolizumab for Renal Cell Carcinoma

Recruiting in Palo Alto (17 mi)

Overseen by Bilal Rahim, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1 & 2

Recruiting

Sponsor: Mohammed Milhem

Must not be taking: CYP3A4 drugs

Disqualifiers: Pregnancy, Breastfeeding, CNS metastases, others

No Placebo Group

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

The purpose of this research study is to test the safety and effectiveness of Seleno-L Methionine (SLM) when combined with the standard dose and schedule of Axitinib and Pembrolizumab in patients who have locally advanced or metastatic clear cell renal cell carcinoma (ccRCC).

Will I have to stop taking my current medications?

The trial does not specify if you need to stop all current medications, but you cannot take drugs that affect the enzyme CYP3A4, like certain antibiotics and antifungals. It's best to discuss your current medications with the trial team.

What data supports the effectiveness of the drug combination Axitinib and Pembrolizumab for Renal Cell Carcinoma?

Research shows that the combination of Axitinib and Pembrolizumab has a 73% response rate in patients with advanced renal cell carcinoma, and it improves overall survival and progression-free survival compared to another drug, sunitinib, in patients with metastatic renal cell carcinoma.

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What safety data exists for the combination of Axitinib and Pembrolizumab in treating renal cell carcinoma?

The combination of Axitinib and Pembrolizumab has been studied for safety in patients with advanced renal cell carcinoma. Common side effects include diarrhea, high blood pressure, fatigue, decreased appetite, nausea, voice changes, hand-foot syndrome (redness and swelling of the hands and feet), and hypothyroidism (underactive thyroid). These side effects were generally manageable.

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How is the drug combination of Axitinib and Pembrolizumab unique for treating renal cell carcinoma?

The combination of Axitinib and Pembrolizumab is unique because it is a standard first-line treatment for advanced renal cell carcinoma, offering a high response rate of 73% in previously untreated patients. This combination works by targeting both the blood vessels that supply the tumor and the immune system to enhance the body's ability to fight cancer.

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Eligibility Criteria

This trial is for adults with advanced or metastatic clear cell renal cell carcinoma (ccRCC) who haven't been treated for it in the metastatic setting. They must be physically active or able to do light work, have normal organ function, controlled blood pressure, and agree to use effective contraception. Those with other cancers, untreated brain metastases, recent major surgery, HIV/AIDS complications, or needing certain drugs are excluded.

Inclusion Criteria

I agree to use effective birth control during and 6 months after the study.

Written and voluntary informed consent

My liver tests are within the required limits, even with liver metastases.

Exclusion Criteria

My eligibility is not affected by my sex, race, or ethnicity.

I haven't had a heart attack, severe chest pain, heart failure, or stroke in the last 6 months.

I am not using, nor will I need, strong medication that affects liver enzymes.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Escalation Part 1

Dose-escalation study to find the maximum tolerated dose (MTD) of Seleno-L Methionine (SLM)

Varies

Multiple visits (in-person)

Expansion Part 2

Participants receive SLM and Axitinib orally, and Pembrolizumab intravenously at the start of each 21-day cycle

21-day cycles

Every 21 days (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 3 years

Participant Groups

The study tests the safety and effectiveness of Seleno-L Methionine (SLM) combined with standard doses of Axitinib and Pembrolizumab in treating ccRCC. It aims to see if adding SLM improves outcomes compared to just Axitinib and Pembrolizumab.

Group I: Seleno-L Methionine (SLM) in Combination with Axitinib and Pembrolizumab Experimental Treatment 3 Interventions

SLM only will be taken by mouth during a two-week run in period. Then patients will receive SLM and Axitinib drugs by mouth, and Pembrolizumab intravenously (IV), at the start of each 21 day cycle.

Axitinib is already approved in European Union, United States, United Kingdom for the following indications:

🇪🇺 Approved in European Union as Inlyta for:

• Renal cell carcinoma

🇺🇸 Approved in United States as Inlyta for:

• Advanced renal cell carcinoma

🇬🇧 Approved in United Kingdom as Inlyta for:

• Advanced renal cell carcinoma

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

University of Iowa Hospitals & Clinics Iowa City, IA

Who Is Running the Clinical Trial?

Mohammed Milhem Lead Sponsor

Bilal G. Rahim Lead Sponsor

Yousef Zakharia Lead Sponsor

University of Iowa Collaborator

References

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

Angiogenic and Immune-Related Biomarkers and Outcomes Following Axitinib/Pembrolizumab Treatment in Patients with Advanced Renal Cell Carcinoma. [2023] Combined axitinib/pembrolizumab is approved for advanced renal cell carcinoma (aRCC). This exploratory analysis examined associations between angiogenic and immune-related biomarkers and outcomes following axitinib/pembrolizumab treatment.

2. Switzerland pubmed.ncbi.nlm.nih.gov

Real-World Therapy Management and Outcomes of First-Line Axitinib Plus Pembrolizumab in Patients With Advanced Renal Cell Carcinoma in the United States. [2022] Combination axitinib plus pembrolizumab is a standard of care in the first-line treatment of patients with advanced clear cell renal cell carcinoma (RCC). This analysis describes the clinical characteristics, treatment management and outcomes of patients receiving first-line (1L) axitinib plus pembrolizumab in a real-world US setting.

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

Extended follow-up from JAVELIN Renal 101: subgroup analysis of avelumab plus axitinib versus sunitinib by the International Metastatic Renal Cell Carcinoma Database Consortium risk group in patients with advanced renal cell carcinoma. [2023] We report updated data for avelumab plus axitinib versus sunitinib in patients with advanced renal cell carcinoma from the third interim analysis of the phase III JAVELIN Renal 101 trial.

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

Axitinib plus Pembrolizumab Is Effective in Renal Cell Carcinoma. [2019] Axitinib plus pembrolizumab has a 73% response rate in previously untreated advanced renal cell carcinoma.

5. Japan pubmed.ncbi.nlm.nih.gov

Pembrolizumab plus axitinib versus sunitinib in metastatic renal cell carcinoma: outcomes of Japanese patients enrolled in the randomized, phase III, open-label KEYNOTE-426 study. [2022] In the phase III open-label KEYNOTE-426 (NCT02853331) study, first-line pembrolizumab and axitinib improved overall survival (OS) and progression-free survival (PFS) versus sunitinib for metastatic renal cell carcinoma (mRCC). KEYNOTE-426 evaluated patients enrolled from 25 sites in Japan.

6. New Zealand pubmed.ncbi.nlm.nih.gov

Axitinib: a review in advanced renal cell carcinoma. [2018] Axitinib (Inlyta(®)) is a potent, selective inhibitor of vascular endothelial growth factor receptor-1, -2 and -3. This article reviews the clinical efficacy and tolerability of axitinib in patients with previously-treated advanced renal cell carcinoma (RCC), as well as summarizing its pharmacological properties. Axitinib was effective in the second-line treatment of advanced RCC, according to the results of the pivotal, phase III AXIS trial. Median progression-free survival (PFS) was significantly prolonged with axitinib versus sorafenib (primary endpoint; independent review committee assessment); this PFS benefit was seen in patients who had received prior treatment with cytokines or sunitinib. The objective response rate was also significantly higher with axitinib than with sorafenib, with no significant between-group difference in median overall survival. Axitinib had a manageable tolerability profile in the AXIS trial, with the most commonly reported treatment-related adverse events including diarrhoea, hypertension, fatigue, decreased appetite, nausea, dysphonia, hand-foot syndrome and hypothyroidism. In conclusion, axitinib is an important option in previously-treated patients with advanced RCC.

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

Outcomes With Combination Pembrolizumab and Axitinib in Second and Further Line Treatment of Metastatic Renal Cell Carcinoma. [2023] Combination immune checkpoint inhibitors (ICI) and vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGF-R-TKI), including pembrolizumab/axitinib, are approved for first-line treatment of metastatic renal cell carcinoma (mRCC). Pembrolizumab/axitinib is associated with superior progression free survival (PFS), objective response rate (ORR), and overall survival over sunitinib. However, to date, the activity and safety of pembrolizumab/axitinib in later lines of therapy has not been reported.

8. England pubmed.ncbi.nlm.nih.gov

Axitinib plus pembrolizumab in patients with advanced renal-cell carcinoma: Long-term efficacy and safety from a phase Ib trial. [2021] Axitinib plus pembrolizumab showed superior overall survival (OS), progression-free survival (PFS) and objective response rate (ORR) versus sunitinib in a randomised phase III trial in patients with advanced renal-cell carcinoma (RCC). We report long-term efficacy and safety of the axitinib/pembrolizumab from the phase I trial (NCT02133742), after 46-55 months from study initiation (data cut-off date, 23rd July 2019).