What is the mechanism of action of this treatment?

Pembrolizumab is a PD-1 inhibitor that enhances the immune system's ability to recognize and attack cancer cells by blocking the PD-1 pathway, which tumors use to evade immune detection. Lenvatinib is a tyrosine kinase inhibitor that targets multiple receptors involved in tumor growth and angiogenesis, such as VEGFR, FGFR, and PDGFR. The combination of Pembrolizumab and Lenvatinib provides a dual approach by both stimulating the immune response and inhibiting tumor growth pathways. This multifaceted mechanism is crucial for kidney cancer patients as it can lead to higher response rates and improved outcomes compared to single-agent therapies.

What side effects are associated with this type of intervention?

Common treatments for kidney cancer, such as Pembrolizumab (a PD-1 inhibitor) and the combination of Pembrolizumab with Lenvatinib (a PD-1 inhibitor and Tyrosine Kinase Inhibitor), have known side effects. Pembrolizumab alone can cause immune-related adverse effects like pneumonitis, colitis, hepatitis, endocrinopathies, and skin reactions. When combined with Lenvatinib, additional side effects may include hypertension, diarrhea, fatigue, decreased appetite, and proteinuria. Severe adverse effects are less common but can occur.

What prior FDA approvals exist?

Pembrolizumab, a PD-1 inhibitor, has been approved by the FDA for the treatment of various cancers, including renal cell carcinoma. The combination of pembrolizumab with lenvatinib, a tyrosine kinase inhibitor, has also been studied and shown efficacy in treating advanced renal cell carcinoma. This combination leverages the immune-modulating effects of pembrolizumab and the anti-angiogenic properties of lenvatinib to improve patient outcomes. Other similar treatments include nivolumab (another PD-1 inhibitor) often used in combination with ipilimumab (a CTLA-4 inhibitor) for advanced renal cell carcinoma.

What other types of research exist?

Promising alternatives to Pembrolizumab and Pembrolizumab with Lenvatinib for kidney cancer patients include: 1) Nivolumab plus Ipilimumab, which has shown durable long-term responses and improved quality of life. 2) Cabozantinib in combination with Atezolizumab, which has demonstrated efficacy in advanced renal cell carcinoma. 3) Nivolumab monotherapy, particularly for patients who have progressed on VEGFR inhibitors, as it improves overall survival and quality of life.

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Pembrolizumab + Lenvatinib for Kidney Cancer

Phase < 1

Recruiting

Led By Vivek Narayan, MD

Research Sponsored by Abramson Cancer Center of the University of Pennsylvania

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Adequately controlled BP with or without antihypertensive medications

Histologically or cytologically confirmed diagnosis of renal cell carcinoma based on newly obtained renal mass core biopsy

Must not have

Clinically significant cardiovascular disease within 12 months from first dose of study intervention

Known history of Hepatitis B or known active Hepatitis C virus infection

Timeline

Screening 3 weeks

Treatment Varies

Follow Up approximately 18-24 months

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing a new treatment alone or in combination with another treatment in kidney cancer patients to see if these treatments improve the body's defense system against cancer around the time of surgery. The treatments help the body attack cancer and stop its growth. These treatments have shown promising results in various cancers, especially kidney cancer.

Who is the study for?

Adults with confirmed renal cell carcinoma, eligible for kidney cancer surgery, can join this trial. They must have good organ function and controlled blood pressure, not be pregnant or breastfeeding, use effective contraception if applicable, and have no recent major surgeries or active infections. Those with certain heart conditions, other cancers within 3 years, severe drug allergies or immune diseases are excluded.

What is being tested?

The study tests pembrolizumab (infusion) alone or combined with lenvatinib (tablet) on the body's immune response to kidney cancer before and after surgical removal of the tumor. The goal is to see how these drugs affect the disease when used as a pre-surgery treatment.

What are the potential side effects?

Pembrolizumab may cause immune-related side effects like inflammation in organs and infusion reactions; lenvatinib might lead to high blood pressure, fatigue, digestive issues such as diarrhea and nausea. Both drugs could potentially increase bleeding risk.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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My blood pressure is under control, with or without medication.

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My kidney cancer diagnosis was confirmed through a biopsy.

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I am fully active and can carry on all pre-disease activities without restriction.

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My kidney cancer is at a stage where surgery is possible.

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I am 18 or older with a confirmed diagnosis of kidney cancer.

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I agree to avoid sex or use birth control during and after the study.

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I am not pregnant or breastfeeding and will use effective birth control or remain abstinent.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I haven't had serious heart problems in the last year.

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I have a history of Hepatitis B or an active Hepatitis C infection.

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I have been treated with cancer-fighting drugs before.

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I have an immune system disorder or I am on long-term steroids.

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I have been diagnosed with HIV.

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I have received an organ or tissue transplant from another person.

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I need surgery urgently.

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I have or had lung inflammation that needed steroids.

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I am currently on medication for an infection.

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My scans show cancer has spread to distant parts of my body.

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I have a severe fistula.

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I am a woman and my pregnancy test is positive.

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My heart's pumping ability is reduced.

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I have another cancer that is getting worse or was treated in the last 3 years.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ approximately 18-24 months

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~approximately 18-24 months

This trial's timeline: 3 weeks for screening, Varies for treatment, and approximately 18-24 months for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Change in frequency of progenitor exhausted CD8 T cells (TEX prog) in peripheral blood during neoadjuvant pembrolizumab +/- lenvatinib and in tumor tissue.

Secondary study objectives

Brisk TIL

Change in Ki67 expression

Immune-Related Pathologic Response (irPR)

+2 more

Other study objectives

Disease-free survival (DFS)

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

2Treatment groups

Experimental Treatment

Group I: B: PembrolizumabExperimental Treatment1 Intervention

Subject will receive Pembrolizumab 200 mg or 400 mg will be administered as a 30-minute IV infusion every 3 weeks.

Group II: A: Pembrolizumab + LenvatinibExperimental Treatment2 Interventions

Subjects will receive Pembrolizumab + Lenvatinib. Pembrolizumab 200 mg or 400 mg will be administered as a 30-minute IV infusion every 3 weeks. Lenvatinib 20 mg daily will be self-administered PO by subject for 28 consecutive days, beginning Day -7.

0 / 21Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Pembrolizumab is a PD-1 inhibitor that enhances the immune system's ability to recognize and attack cancer cells by blocking the PD-1 pathway, which tumors use to evade immune detection. Lenvatinib is a tyrosine kinase inhibitor that targets multiple receptors involved in tumor growth and angiogenesis, such as VEGFR, FGFR, and PDGFR. The combination of Pembrolizumab and Lenvatinib provides a dual approach by both stimulating the immune response and inhibiting tumor growth pathways. This multifaceted mechanism is crucial for kidney cancer patients as it can lead to higher response rates and improved outcomes compared to single-agent therapies.