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A study of pembrolizumab, belzutifan, and lenvatinib before main treatment in patients with localized kidney cancer

Verified siteRegistered drugNo placebo

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What is this trial about?

A plain-language summary of the goals, design and what participants do

This study focuses on individuals with renal cell carcinoma, which is a type of kidney cancer that has not yet spread to other parts of the body. The purpose of this study is to evaluate how different drug combinations affect the size of the tumor before the main surgical treatment is performed. This initial phase of treatment is known as neoadjuvant therapy, meaning the medications are given to shrink the tumor before surgery.

Participants will receive different combinations of medications. One group will receive pembrolizumab and belzutifan, while others may also receive lenvatinib. These drugs are administered through different methods: pembrolizumab is given as an intravenous infusion, which is a liquid medicine delivered directly into a vein, while belzutifan and lenvatinib are taken as pills or capsules by mouth. Some participants may receive a placebo instead of one of the active medications to allow for a comparison between the different treatment groups.

During the study, the effectiveness of the treatment is monitored using a computed tomography scan, commonly known as a CT scan, which uses special X-rays to create detailed pictures of the inside of the body. These scans help to determine if the tumor has decreased in size. The study also tracks how participants feel and any side effects that may occur during the course of the medication.

The research process

The trial runs in 4 steps – from screening to follow-up. Each step says what happens and what the team monitors.

Step 1
Initiation of treatment
The neoadjuvant treatment, which refers to therapy given before the main surgery, begins.
The treatment involves a combination of medications to address localized renal cell carcinoma, a type of kidney cancer.
Step 2
Medication administration
The pembrolizumab is administered as an intravenous infusion, which means it is delivered directly into a vein, at a dose of 400 mg.
The belzutifan is taken as an oral film-coated tablet at a dose of 120 mg.
Depending on the assigned group, lenvatinib is also taken as an oral capsule at a dose of 20 mg.
Step 3
Monitoring and imaging
At week 12, a ct scan, which is a detailed medical image of the body, is performed to measure any changes in the size of the tumor.
The results are used to determine the radiographic response, which is assessed by checking if the tumor size has decreased by at least 30%.
Step 4
Follow-up and surgical assessment
The course includes monitoring for adverse events, which are side effects or unwanted medical occurrences.
Any delays in surgery lasting longer than 4 weeks due to side effects are recorded.
Health status and physical functioning are tracked through patient reported outcomes, which are assessments based on personal experiences of health and well-being.

Who can join the trial?

18 criteria

Participants must be at least 18 years old on the day they sign the agreement to join the study.
Men must agree to use specific contraception (methods to prevent pregnancy, such as condoms) or remain abstinent from sex for the duration of the study and for at least 7 days after the last dose of the study medicines.
Women must not be pregnant or breastfeeding and must use highly effective contraception or remain abstinent for a specific period after treatment ends.
Women must have a negative pregnancy test (a test showing no pregnancy) within 24 hours before the first dose.
The participant or their legal representative must provide written informed consent, which is a signed document showing they understand and agree to take part in the study.
Blood pressure must be well-controlled, meaning it must be 150/90 mmHg or lower, with or without the use of antihypertensive medications (drugs used to lower high blood pressure).
Participants must have adequate organ function, meaning their internal organs like the liver or kidneys are working properly, as confirmed by laboratory tests (medical tests on blood or urine).
Participants with Hepatitis B (HBV) are eligible if they have been on antiviral therapy (medicine to fight the virus) for at least 4 weeks and have an undetectable viral load (the amount of virus in the blood is so low it cannot be measured).
Participants with Hepatitis C (HCV) are eligible if they have completed treatment and have an undetectable viral load.
Participants living with HIV must have the virus well-controlled using antiretroviral therapy (ART), with a CD4+ T-cell count (a type of immune cell used to measure immune strength) of 350 or higher and a very low amount of the virus in the blood.
The patient must have a confirmed diagnosis of renal cell carcinoma (a type of kidney cancer) that includes a clear cell component (a specific type of cell seen under a microscope).
The cancer must meet specific TNM staging requirements, which is a system doctors use to describe the size and spread of a tumor.
The cancer must be measurable, meaning it is large enough to be clearly seen and tracked on medical scans.
A tissue sample (such as a biopsy, which is a small piece of the tumor removed for testing) must be provided for examination.
A surgeon must confirm that the patient is a candidate for curative intent surgery, which is an operation intended to remove all the cancer.
Any adverse events (side effects or health problems) from previous treatments must have mostly resolved or returned to a baseline (the patient's normal health state).
The patient must have an ECOG performance score of 0 or 1, which is a scale used to measure how well a person can perform daily activities while having cancer.
The patient must have a KPS score (Karnofsky Performance Status) of at least 70%, which is another scale used to measure a patient's ability to care for themselves and function.

Who cannot join the trial?

27 criteria

You have evidence that the cancer has spread to other parts of the body, known as metastatic disease.
You have a history of or currently have pneumonitis or interstitial lung disease, which are conditions involving inflammation or scarring of the lung tissue, especially if you needed steroids (medicines used to reduce inflammation) to treat it.
Your blood oxygen levels are low, specifically a pulse oximeter reading (a device that measures oxygen in the blood) below 92%, or you require supplemental oxygen (extra oxygen provided through a mask or tube) on an ongoing basis.
You have an active infection that requires intravenous therapy (medicine delivered directly into a vein).
You have moderate to severe hepatic impairment, which means your liver is not functioning properly, specifically categorized as Child-Pugh B or C (a system used to grade the severity of liver disease).
You have an active infection of Hepatitis B or Hepatitis C (viruses that affect the liver).
You have proteinuria, which is an abnormally high amount of protein in your urine.
You have had major surgery within the 3 weeks before your first dose of the study treatment, or your surgical wound has not healed properly.
You have any medical condition, treatment, or laboratory result that might make it difficult to participate in the study or make the results unclear.
You have known psychiatric disorders (mental health conditions) or substance abuse issues that could prevent you from following the study requirements.
You are pregnant, breastfeeding, planning to become pregnant, or planning to have a child during the study period.
You have previously used certain types of immunotherapy, which are medicines that help the immune system fight cancer, such as anti-PD-1, anti-PD-L1, anti-PD-L2, or other drugs that target T-cell receptors.
You have had an allogenic transplant, which means receiving an organ or tissue from another person.
You have a fistula, which is an abnormal connection or tunnel between two organs or between an organ and the skin, that is severe (Grade 3).
Your heart's pumping strength, known as the left ventricular ejection fraction (LVEF), is below the normal range as measured by an echocardiogram (an ultrasound of the heart) or a MUGA scan (a specialized heart imaging test).
You have a prolongation of the QTcF interval, which means the electrical activity of your heart is taking longer than normal to reset between beats.
You have significant cardiovascular disease (heart disease) within the last 12 months, such as congestive heart failure (the heart cannot pump enough blood), unstable angina (chest pain), a myocardial infarction (heart attack), a cerebral vascular accident (stroke), or an arrhythmia (irregular heartbeat) that causes instability.
You have had hemoptysis, which is coughing up bright red blood, within 3 weeks of starting the study treatment.
You have gastrointestinal malabsorption, which means your digestive system cannot properly absorb nutrients, or any other condition that might prevent the body from absorbing the study drug lenvatinib.
You are taking certain strong or moderate CYP3A4 inducers, which are medicines that speed up how your body processes certain drugs, such as phenobarbital or rifampicin, and cannot stop taking them.
You have received any systemic anti-cancer therapy (cancer treatment that travels through the whole body) within the last 3 years.
You have another type of cancer that is growing or has required treatment within the past 3 years, though certain skin cancers or low-risk prostate cancers are allowed.
You have received a live vaccine (a vaccine containing a weakened form of the germ) within 30 days before starting the study.
You have used an investigational agent (an experimental drug) or investigational device (an experimental tool) within the 4 weeks before the study begins.
You have a diagnosis of immunodeficiency (a weakened immune system) or are taking systemic steroid therapy (medicines like prednisone) or other immunosuppressive therapy (medicines that lower immune system activity) within 7 days of the study.
You have a severe hypersensitivity (allergic reaction) to the study drugs pembrolizumab, lenvatinib, or belzutifan.
You have an active autoimmune disease (a condition where the immune system attacks the body) that required immunosuppressive treatment in the last 2 years.

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Verified sites

All sites with verified contact details – recruitment status may not be available; ask directly

Hospital Clinic De Barcelona
Verified
Barcelona, Spain
Hospital General Universitario De Valencia
Verified
Valencia, Spain
Hospital Universitario 12 De Octubre
Verified
Madrid, Spain

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Investigated drugs

Lenvatinib
is an oral capsule used in this study to help stop the growth of cancer cells by blocking certain signals that tumors use to develop new blood vessels.
Belzutifan
is an oral tablet that works by targeting a specific protein that helps tumors grow and survive, which can help limit the progression of the cancer.
Pembrolizumab
is a medication given through an intravenous infusion that helps the body's own immune system recognize and attack cancer cells more effectively.

What is already known about the treatment

Lenvatinib
This medication is taken by mouth in the form of a capsule. It is an established cancer treatment used to help stop the growth of certain tumors by blocking specific proteins that help blood vessels supply nutrients to cancer cells. As a type of targeted therapy, it works by interfering with the signals that tumors use to grow and spread.
Belzutifan
This drug is administered orally as a film-coated tablet. It is a newer medication used to treat certain types of tumors by targeting a specific protein called HIF-2 alpha that helps cancer cells survive in low-oxygen environments. It belongs to a class of drugs known as HIF-2 alpha inhibitors, which work by preventing the protein from triggering the growth of tumor cells.
Pembrolizumab
This medication is given through an intravenous infusion directly into a vein. It is a widely used treatment for various types of cancer that works by helping the body's own immune system recognize and attack cancer cells. It is classified as an immunotherapy, specifically an immune checkpoint inhibitor, which functions by removing the "brakes" that cancer cells use to hide from the immune system.

Investigated diseases

Renal cell carcinoma - This is a type of cancer that starts in the cells of the kidney. It often begins as a mass or tumor within the kidney tissue. As the disease progresses, the abnormal cells multiply and can increase the size of the tumor. If left unchecked, the cancerous cells may spread beyond the kidney to other parts of the body.