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Efficacy of pembrolizumab drug combination in advanced renal cell carcinoma: early prediction using serum KIM-1 and MAdCAM-1

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

The study looks at people with advanced renal cell carcinoma. It tests a combination of medicines that includes the immune‑system drugs pembrolizumab and nivolumab together with the targeted medicines cabozantinib and lenvatinib. Blood proteins called KIM-1 and MAdCAM-1 are measured early to see if they can predict how well the treatment works. The purpose of the study is to find out whether early changes in these proteins are linked to the effect of reducing or stopping part of the combination therapy on the chance of remaining free of disease progression for 12 months.

Participants start with the full combination of medicines given by infusion (through a vein) and pills taken by mouth. After a short initial period, they are randomly assigned either to continue the full combination or to switch to a less intensive regimen. Blood samples are taken at the start and again at the time of randomization to track the protein levels. Follow‑up visits occur regularly to monitor disease status, overall health, quality of life, and any side effects, and the study continues for at least a year after the randomization point.

The research process

The trial runs in 8 steps – from screening to follow-up. Each step says what happens and what the team monitors.

  1. Step 1

    Baseline Visit

    You will attend a first study visit after joining the trial. During this visit, blood will be drawn to measure the proteins KIM-1 and MAdCAM-1, which are being studied as early indicators of treatment response.

    Imaging tests such as a CT scan will be performed to document the current extent of the kidney cancer. The results will be evaluated using the RECIST 1.1 criteria, a standard method for measuring tumor size.

    You will complete questionnaires about your quality of life and emotional wellbeing, including the EORTC QLQ‑C30 and HADS scales.

  2. Step 2

    Start Combination Infusion Therapy

    You will begin receiving two intravenous infusions:

    Pembrolizumab (KEYTRUDA) – 200 mg given as a solution for infusion.

    Nivolumab (OPDIVO) – 480 mg given as a solution for infusion.

    Both medicines are administered through a vein by a qualified professional. The exact schedule (for example, every three weeks) will follow the study protocol and will continue until the randomization point.

  3. Step 3

    Regular Monitoring Visits

    At scheduled intervals you will return for follow‑up visits. Each visit includes:

    A blood draw to re‑measure KIM-1 and MAdCAM-1 levels.

    Repeat imaging to check for any change in tumor size.

    Completion of the same quality‑of‑life questionnaires used at baseline.

    Assessment for any side effects or adverse events, recorded using the CTCAE v5.0 grading system.

  4. Step 4

    Randomization

    After the early monitoring period, the study team will assign you to one of two groups based on the trial’s randomization process:

    Continue the combination of pembrolizumab and nivolumab, or

    Switch to a de‑escalated oral treatment.

  5. Step 5

    Continue Combination Therapy (If Assigned)

    You will keep receiving the same intravenous infusions of pembrolizumab 200 mg and nivolumab 480 mg at the schedule defined by the protocol.

    Monitoring visits, imaging, blood tests, and questionnaires will continue as described in step 3.

  6. Step 6

    Start De‑escalated Oral Therapy (If Assigned)

    You will begin taking an oral medication once daily:

    Either cabozantinib (CABOMETYX) – 40 mg film‑coated tablet, or

    Either lenvatinib (Kisplyx) – 20 mg hard capsule.

    The tablet or capsule is swallowed with water. The oral therapy will be continued until the end of the study, disease progression, or discontinuation for safety reasons.

    You will still attend regular monitoring visits for imaging, blood tests, questionnaires, and safety assessments.

  7. Step 6

    Ongoing Assessments Until Study End

    Throughout the remainder of the trial you will have periodic visits that include:

    Imaging to evaluate tumor status.

    Blood draws for KIM-1 and MAdCAM-1 and other safety labs.

    Quality‑of‑life questionnaires.

    Evaluation of any side effects, using the CTCAE v5.0 grading system.

  8. Step 7

    Final Evaluation

    At 12 months after randomization, or earlier if disease progression occurs, a final assessment will be performed.

    The primary outcome is whether the disease has progressed, according to RECIST 1.1 criteria, or if death has occurred within the 12‑month period.

    Overall survival, quality‑of‑life scores, and any treatment‑emergent adverse events will also be recorded.

Who can join the trial?

9 criteria

  • Be at least 18 years old when signing the consent form.
  • Have a doctor‑confirmed diagnosis of clear‑cell renal cell carcinoma (the type of kidney cancer seen under a microscope).
  • Have cancer that is either locally advanced (grown large in the kidney area) or metastatic (spread to other parts of the body) and cannot be cured with surgery.
  • Fit into a favorable or intermediate risk group according to the IMDC scoring system (a tool doctors use to estimate how aggressive the cancer is).
  • Have disease that can be measured on imaging tests (like CT scans) using the standard rules called RECIST version 1.1.
  • Be able to receive first‑line systemic treatment (the first medicines given for the cancer) with either pembrolizumab plus lenvatinib or nivolumab plus cabozantinib (specific cancer‑fighting drugs).
  • Have an ECOG performance status of 0 to 2, which means you are fully active (0) to able to care for yourself but unable to do strenuous work (2).
  • Show adequate bone marrow (blood‑forming tissue), hepatic (liver), and renal (kidney) function as defined by the study’s lab tests.
  • Provide a written informed consent agreeing to take part in the study.

Who cannot join the trial?

9 criteria

  • Being in a poor‑risk group according to the IMDC criteria, which is a system doctors use to estimate the outlook for kidney cancer.
  • Having already received systemic (body‑wide) treatment for advanced or metastatic kidney cancer, meaning the cancer has spread beyond the kidney.
  • Having a known contraindication (a reason you should not take the study medicines), which include the immune‑checkpoint inhibitor (ICI) or the targeted drug (TKI).
  • Having other active health problems that are not well controlled and could put you at risk or make it hard to understand the study results.
  • Having symptoms from, or untreated, cancer spread to the brain or spinal cord (central nervous system or CNS metastases), or having brain/spinal cancer that is not stable.
  • Having another current cancer that could affect the study results, unless that other cancer has been treated well and is very unlikely to interfere.
  • Being pregnant or breastfeeding.
  • Being able to become pregnant and not willing to use reliable contraception (birth control) during the study and for the required time after stopping treatment.
  • Being unable to understand the study information or to sign the written informed consent form.
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Investigated drugs

  • pembrolizumab

    is a medicine given through an IV that helps the body’s own immune system see and attack kidney cancer cells. It works by blocking a “brake” on immune cells, allowing them to be more active against the tumor.

  • nivolumab

    is also given by IV and works in a similar way to pembrolizumab. It releases a different “brake” on the immune system, helping immune cells recognize and destroy cancer cells more effectively.

  • cabozantinib

    is a pill taken by mouth that blocks several signals that tumors use to grow and spread. By stopping these signals, the drug can slow down the growth of kidney cancer and may shrink tumors.

  • lenvatinib

    is a capsule taken by mouth that blocks proteins involved in forming new blood vessels that feed the tumor and also stops signals that help cancer cells multiply. This helps to limit tumor growth.

What is already known about the treatment

  • KEYTRUDA

    This medication is given as a solution that is slowly injected into a vein (intravenous infusion). It is an approved drug that is widely used and described in many medical studies. It is mainly used to treat advanced kidney cancer and other cancers by blocking a protein called PD‑1, which helps the immune system recognize and attack cancer cells. It belongs to the class of immune checkpoint inhibitors, specifically PD‑1 inhibitors.

  • OPDIVO

    This drug is also administered as a liquid that is infused into a vein over a set period of time. It is an approved therapy with extensive documentation in the medical literature. It is used for advanced kidney cancer and works by attaching to the PD‑1 protein on immune cells, preventing cancer cells from turning off the immune response. It is classified as an immune checkpoint inhibitor, a PD‑1 blocker.

  • CABOMETYX

    The medication comes as film‑coated tablets that are swallowed whole (oral tablet). It is an approved cancer drug that has been studied in many clinical trials. It is used to treat advanced kidney cancer and works by blocking several enzymes (tyrosine kinases) that help tumors grow new blood vessels and spread. It is classified as a multi‑target tyrosine kinase inhibitor.

  • Kisplyx

    This product is provided as hard capsules that are taken by mouth (oral capsule). It is an approved medication with a solid record in scientific research. It is used for advanced kidney cancer and works by inhibiting several tyrosine kinases, including those that control blood vessel formation and tumor growth. It belongs to the class of multi‑target tyrosine kinase inhibitors.

Investigated diseases

Renal cell carcinoma - Renal cell carcinoma is a type of kidney cancer that originates in the lining of the small tubes within the kidney. It usually begins as a small, localized tumor and may grow slowly at first. Over time the tumor can enlarge and invade nearby tissues such as the adrenal gland or blood vessels. Cancer cells can also spread through the bloodstream to distant organs, most commonly the lungs, bones, and liver. The disease is monitored by imaging and clinical assessment to track any growth or spread.
Trial detailsLast updated 25 Oct 2026
Age18+ yearsPhasePhase IITrial ID2026-525749-54-00Protocol codeORI2026-15Estimated enrolment150 patientsSponsorInstitute Of Oncology Ljubljana

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