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Efficacy Comparison of Zanzalintinib (XL092) and Pembrolizumab Versus Pembrolizumab Monotherapy in PD-L1 Positive Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma

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What is this trial about?

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

This clinical trial is focused on studying a type of cancer known as recurrent or metastatic head and neck squamous cell carcinoma. This is a condition where cancer cells form in the tissues of the head and neck and have either returned after treatment or spread to other parts of the body. The study will explore the effectiveness of a new treatment combination involving two medications: zanzalintinib (XL092) and pembrolizumab. Pembrolizumab is already used in cancer treatment, while zanzalintinib is being tested for its potential benefits when used together with pembrolizumab.

The purpose of the study is to compare how well the combination of zanzalintinib and pembrolizumab works against using pembrolizumab alone in treating this type of cancer. Participants in the study will be randomly assigned to receive either the combination treatment or pembrolizumab by itself. Some participants may receive a placebo, which looks like the real medication but does not contain the active drug. The study will involve regular check-ups and monitoring to assess the treatment's effects and any side effects experienced by the participants.

The study will take place over several months, with participants receiving treatment and being monitored for changes in their condition. The goal is to determine if the combination of zanzalintinib and pembrolizumab can improve outcomes for patients with this type of cancer. Participants will be closely observed by medical professionals throughout the study to ensure their safety and to gather important data on the treatment's effectiveness.

The research process

The trial runs in 3 steps – from screening to follow-up. Each step says what happens and what the team monitors.

  1. Step 1

    Study participation

    Participation begins with the assignment to a specific treatment group. this is done through a randomized process, meaning the group is chosen by chance, and a double-blind process, which means neither the patient nor the medical staff knows which specific treatment is being administered during the study.

  2. Step 2

    Treatment administration

    Treatment involves receiving one of two options. one option is the combination of xl092 and pembrolizumab, while the other option is pembrolizumab alone.

    xl092 is taken as a 100 mg tablet by mouth.

    pembrolizumab is administered as a 200 mg solution through an intravenous infusion, which is a method of delivering medicine directly into a vein.

  3. Step 3

    Monitoring and evaluation

    Regular monitoring is conducted to track the progression-free survival, which measures the length of time during and after treatment that the disease does not get worse.

    Health status is assessed by checking for adverse events, which are side effects or medical problems that may occur during the study.

    Medical checks are performed to observe changes in laboratory parameters, such as blood test results, and vital signs, such as blood pressure and heart rate.

Who can join the trial?

11 criteria

  • You must have head and neck squamous cell carcinoma (a type of cancer that starts in the skin or cells of the head and neck area) that has returned or spread to other parts of the body, and which cannot be cured by local treatments like surgery or radiation.
  • The cancer must be located in the oropharynx (the back of the throat), oral cavity (the mouth), hypopharynx (the lower part of the throat), or larynx (the voice box).
  • You must not have received any systemic therapy (medicine that travels through the whole body, such as chemotherapy) to treat the cancer after it returned or spread.
  • If you received treatment for advanced cancer in the past, it must have been completed more than 6 months before joining this study.
  • Your tumor must show a PD-L1 expression level (a protein on certain cells) with a Combined Positive Score (CPS) of 1 or higher.
  • If your cancer is in the oropharynx, you must have a test result showing your HPV status (testing for the Human Papillomavirus) using p16 testing.
  • A doctor must be able to measure your cancer using specific rules called RECIST 1.1 (a standard method used to measure how much tumor is present).
  • Any side effects from previous treatments must have improved to a Grade 1 severity (mild symptoms) or returned to your normal baseline state.
  • You must be at least 18 years old or the legal age of adulthood in your country.
  • Your ECOG performance status must be 0 or 1, which means you are generally able to carry out most daily activities and are physically active.
  • You must have adequate organ and marrow function (your vital organs and the part of your bone marrow that makes blood cells must be working well).

Who cannot join the trial?

14 criteria

  • Cancer located in the nasopharynx (the upper part of the throat behind the nose), salivary glands, or an occult primary site (a cancer where the original starting location cannot be clearly found).
  • Having had major surgery, such as surgery on the gastrointestinal tract (the digestive system) or the removal/biopsy of brain metastasis (cancer that has spread to the brain), within 8 weeks before being assigned to the study. All wounds must be fully healed.
  • An electrocardiogram (a test that records the electrical activity of the heart) showing a corrected QT interval (a measurement of the time it takes for the heart muscle to recharge between beats) greater than 480 ms.
  • Being pregnant or lactating (breastfeeding).
  • Receiving a live, attenuated vaccine (a type of vaccine that uses a weakened form of the germ) within 30 days before joining the study.
  • Having cancer that can be treated with local therapy (treatment focused on one specific area, like surgery or radiation) with the goal of curative intent (aiming to completely cure the disease).
  • Having previously used certain types of systemic immunotherapy (treatments that help the immune system fight cancer), such as zanzalintinib or drugs targeting PD-1, PD-L1, PD-L2, CTLA-4, OX-40, or CD137, unless specific timing rules regarding surgery are met.
  • Having a life expectancy (how long a person is expected to live) of less than 3 months or having rapidly progressing disease (cancer that is growing or spreading very quickly, such as causing uncontrolled pain).
  • Having progressive disease (cancer that is growing or spreading) within 6 months of finishing previous systemic treatment (medicine that travels through the whole body, like chemotherapy) for head and neck cancer. This must be confirmed by radiographic (imaging like X-rays or CT scans) evidence.
  • Having received radiation therapy for bone metastases (cancer that has spread to the bones) within 2 weeks, or any other radiation within 4 weeks before starting the study.
  • Having ongoing complications from past radiation, such as radiation pneumonitis (inflammation of the lung tissue caused by radiation) or fistulation (the formation of an abnormal connection between organs).
  • Having known brain metastases (cancer that has spread to the brain) or cranial epidural disease (cancer near the protective lining of the brain) unless it has been treated and has been stable (not changing or growing) for at least 4 weeks.
  • Testing positive for the hepatitis B surface antigen, which indicates a hepatitis B infection.
  • Testing positive for the hepatitis C virus antibody, which indicates a hepatitis C infection.
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Investigated drugs

  • XL092

    is an experimental oral tablet being studied for its ability to treat cancer.

  • Pembrolizumab

    is an intravenous medication that helps the body's immune system recognize and attack cancer cells.

What is already known about the treatment

  • XL092

    This medication is taken as a tablet by mouth and is currently being studied in clinical trials to treat advanced cancers. It belongs to a group of drugs known as tyrosine kinase inhibitors, which work by blocking specific proteins that help cancer cells grow and multiply. By targeting these molecular signals, the drug aims to stop the progression of the tumor.

  • Pembrolizumab

    This medicine is administered as a liquid through an intravenous infusion into a vein and is an established treatment for various types of cancer. It is classified as an immunotherapy that works by attaching to specific proteins on immune cells to prevent them from being turned off by cancer cells. This action helps the body's own immune system recognize and attack the cancer more effectively.

Investigated diseases

Recurrent or metastatic head and neck squamous cell carcinoma - This is a type of cancer that begins in the squamous cells lining the head and neck area. It often develops in the mouth, throat, or larynx. The disease is considered recurrent if it returns in the same location after a period of being undetectable. It is considered metastatic when the cancer cells spread from the original site to other parts of the body. This progression involves cells breaking away from the primary tumor and traveling through the blood or lymph system.
Trial detailsLast updated 2 Oct 2026
Age18+ yearsPhasePhase IVTrial ID2023-506308-24-00Protocol codeXL092-305Estimated enrolment190 patientsSponsorExelixis Inc.

sourced from the EU Clinical Trials Register and site verification

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On this site, “treatment” means an investigational medicine being studied in a clinical trial. Its safety and efficacy for the use being studied have not yet been confirmed, some participants may receive a placebo or a comparator medicine, and taking part does not guarantee any health benefit. The decision to take part is made by the doctor at the research site. This site is for information only and does not replace medical advice.

This service is not affiliated with the European Commission, the EMA, or the official CTIS system. Most information comes from publicly available international clinical-trial registries, supplemented by data from academic sites, national regulators and commercial sponsors. On this site, “treatment” and “therapy” mean a medicine being tested in a clinical trial. Its safety and effectiveness in the use being studied are not yet confirmed, some participants may receive a placebo or a comparator, and taking part does not guarantee a health benefit. The doctor at the research site decides who can take part. This site provides information, not medical advice. Certain content and visual elements on this website have been generated or enhanced using artificial intelligence (AI).