Study of ivonescimab alone or with ligufalimab versus pembrolizumab for patients with recurrent or metastatic head and neck squamous cell cancer

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What is this study about?

This study involves patients with squamous cell carcinoma of the head and neck that has come back after treatment or has spread to other parts of the body. Head and neck squamous cell carcinoma is a type of cancer that develops in the moist tissues lining the mouth, throat, voice box, or related areas. The study will test different treatment approaches using medications given through a vein. The treatments being studied include ivonescimab, which is also known by its code name AK112, either used alone or combined with another medication called ligufalimab, which has the code name AK117. These treatments will be compared to a standard treatment called pembrolizumab, which is already approved for use in this type of cancer. All of these medications are types of immunotherapy that work by helping the body’s immune system fight cancer cells.

The purpose of the study is to compare how long patients live when treated with ivonescimab combined with ligufalimab versus pembrolizumab alone, and also to compare ivonescimab alone versus pembrolizumab. The study will only include patients whose tumors test positive for a protein marker called PD-L1, which is measured using a specific scoring system. Patients will be randomly assigned to receive one of the three treatment options, and the study is designed to be open-label, meaning both patients and doctors will know which treatment is being given.

During the study, patients will receive their assigned treatment through an infusion into a vein at regular intervals over a treatment period that can last up to two years. The study doctors will monitor how well the treatment works by checking if tumors shrink or stop growing, and they will also watch for any side effects. Additional assessments will measure how the medications move through the body and whether the immune system develops any reaction to these treatments. Patients participating in this study must not have received previous treatment specifically for their cancer after it has spread or come back, although they may have had earlier treatments when the cancer was first diagnosed.

1 Treatment assignment

After joining the study, you will be assigned to one of three treatment groups. The assignment will be done randomly, which means neither you nor your doctor will choose which treatment you receive.

The three possible treatment groups are: ivonescimab alone, ivonescimab combined with ligufalimab, or pembrolizumab.

2 Treatment administration

You will receive treatment through intravenous infusion, which means the medication will be given directly into your vein through a drip.

The specific medication you receive will depend on which treatment group you were assigned to in step 1.

If you are assigned to receive pembrolizumab, the medication used is called KEYTRUDA, which contains 25 milligrams of the active substance per milliliter of solution.

3 Regular treatment cycles

You will receive treatment in repeated cycles. The exact schedule will be determined based on your assigned treatment group.

Each treatment session will involve receiving the medication through intravenous infusion.

4 Monitoring and assessments

Throughout the study, your health will be monitored regularly through various tests and examinations.

Blood tests will be performed to check your organ function, including tests for your kidneys, liver, and blood cell counts.

Imaging scans will be conducted to measure any changes in your tumor size according to standard criteria called RECIST v1.1.

Your overall physical condition will be assessed using a scoring system called ECOG performance status, which measures how well you can perform daily activities.

5 Safety monitoring

Your safety will be monitored throughout the study by checking for any side effects or adverse reactions to the treatment.

Blood samples will be collected to measure the levels of medication in your body, which is called pharmacokinetic assessment.

Tests will also be performed to check if your body develops an immune response to the medication, which is called immunogenicity assessment.

6 Response evaluation

Your response to treatment will be evaluated regularly to determine if the tumor is shrinking, staying the same, or growing.

The main measurement being tracked is overall survival, which means how long you live after starting treatment.

Other measurements include progression-free survival, which tracks how long you live without the disease getting worse, and objective response rate, which measures whether your tumor shrinks.

Disease control rate will also be measured, which indicates whether the treatment is keeping the disease stable or causing it to shrink.

7 Continued participation

You will continue to receive treatment and attend scheduled visits according to the study protocol.

The study is expected to continue until the end of 2030, though your individual participation length may vary based on your response to treatment and overall health.

Who Can Join the Study?

You must be able to voluntarily give your written permission to participate in the study.
You must have adequate organ function, which means your body organs need to work well enough, including:
- Blood cells: Your blood must have enough white blood cells (cells that fight infection), platelets (cells that help blood clot), and hemoglobin (protein that carries oxygen in red blood cells).
- Kidneys: Your kidneys must work well enough to filter waste from your blood, and you should not have too much protein in your urine.
- Liver: Your liver must work properly, shown by blood tests measuring bilirubin (a substance made when red blood cells break down), AST and ALT (enzymes that show liver health), and albumin (a protein made by the liver).
- Blood clotting: Your blood must clot normally, unless you are already taking blood-thinning medication for medical reasons.
You must be willing and able to follow the study schedule, including visits, treatments, and laboratory tests.
You must be between 18 and 79 years old when you join the study.
Your general health and daily activity level must be good, rated as 0 or 1 on the ECOG scale (a system that measures how cancer affects your daily living abilities).
Your expected survival must be at least 6 months.
Your cancer must be confirmed by laboratory examination of tissue or cells, and it must be recurrent (came back after treatment) or metastatic (spread to other parts of the body) squamous cell carcinoma (a type of cancer) located in the mouth, throat, lower throat, or voice box area.
If your cancer is in the throat area, you must have a test result showing whether your cancer is related to HPV (human papillomavirus, a virus that can cause certain cancers).
You must not have received any previous systemic treatment (treatment affecting the whole body) for your recurrent or metastatic cancer. However, you may have received previous chemotherapy, radiation, or other treatments if your cancer came back more than 6 months after those treatments ended.
You must have at least one tumor that can be measured using imaging scans, and this tumor must be suitable for repeated measurements to track changes.
Your tumor must test positive for a protein called PD-L1 (a protein found on some cancer cells) with a score of at least 1, confirmed by a laboratory test on your tumor tissue sample.

Who Cannot Join the Study?

The source data does not provide specific exclusion criteria for this clinical trial
Exclusion criteria are reasons why someone cannot join a study, but this information was not included in the available trial details
To learn what conditions or situations would prevent participation in this study, you would need to review the complete trial documentation

Where you can join this trial?

Verified and Recommended Sites

No sites found in this category

Verified Sites

Site Name	City	Country
Institut Gustave Roussy	Villejuif	France
University Hospital Of Clermont-Ferrand	Clermont Ferrand	France
CLINIQUE DE LA CÔTE D’EMERAUDE	Saint-Malo	France
Institut De Cancerologie De Lorraine	Vandoeuvre Les Nancy	France
Centre de Radiothérapie Guillaume le Conquérant	Le Havre	France
Centre Hospitalier Intercommunal Creteil	Creteil	France
Hospital Universitario De Salamanca	Salamanca	Spain
Centre Hospitalier Universitaire De Bordeaux	Bordeaux	France
Centre Hospitalier Regional Et Universitaire De Brest	Brest	France
Comite Entreprise Paul Papin	Angers	France
Institut Curie – Site Paris	Paris	France

Other Sites

Site Name	City	Country
Centre Antoine Lacassagne	Nice	France
Hopital Tenon	Paris	France
Centre Hospitalier Universitaire De Nimes	Nimes	France
Institut Sainte Catherine	Avignon	France
Hospital Universitario Virgen De Las Nieves	Granada	Spain
Polyclinique De Blois	La Chaussee St Victor	France
CHP Sainte Marie Osny	Osny	France
Groupement De Cooperation Sanitaire Risssa Recherche & Innovation Sante Sarcelles	Sarcelles	France
Centre Hospitalier Intercommunal Toulon / La Seine-Sur-Mer	Toulon	France
Centre Hospitalier Universitaire De Nantes	Nantes	France
Groupe Hospitalier Bretagne Sud	Lorient	France
Centre Hospitalier Universitaire Amiens Picardie	Amiens	France
Hopital Prive Clairval	Marseille	France
Hopital Beaujon	Clichy	France
Grand Hopital De Charleroi	Charleroi	Belgium
Clinique Victor Hugo	Le Mans	France
Hopital Nord Franche-Comte	Belfort	France
Centre Regional Lutte Contre Le Cancer	STRASBOURG, Alsace	France
Centre Francois Baclesse	Caen	France
Hospital Universitario Virgen De La Victoria	Malaga	Spain
Centre Hospitalier Saint Nazaire	St Nazaire	France
Park Taulí University Hospital	Barcelona	Spain
Irmgaive Rqhdqieu Db Cfxcxv Dt Mxdalpwygxb	Montpellier	France
Cbemkx Lggy Boldjc	Lyon	France
Cqegkf Hbnxezecznu Ufzzgbtpmkxba Rfssn	Reims	France
Cuqmfg Hvmobexomsi Vzqcezr	Valence	France
Hwiqrlv Pnbok Dgfcsiqgtzhom	Valence	France
Clu dobykacfgsaqaz	Epagny Metz Tessy	France
Auumqpzluk Pvirxgwq Hxtgvqbv Dz Mnhczpwln	Marseille	France
Ccexwe Hvebvhnhugh Rlpzqjdj Uvtnymhebgtsn Du Tdjkd	Tours	France
Ibnplfuc Ctfkfd Dinggfqmhzfgusadu	L'hospitalet De Llobregat	Spain
Ffrmaxdzs Pznv Lf Ixxhzdxzdotmr Bfkakgonu Dfu Hrulgvvo Utljazvyfujha Lt Pld	Madrid	Spain
Coxpws Ohwfq Ljqudfw	Lille	France

Trial status

Country	Status	Recruitment Start
Belgium	Not yet recruiting	29.12.2025
France	Recruiting	29.12.2025
Spain	Not yet recruiting	29.12.2025

Trial locations

Investigated drugs:

Ivonescimab is an investigational medication being studied in this trial. It is being tested either alone or in combination with another medication to treat head and neck cancer that has spread or come back.

Ligufalimab is an investigational medication being studied in combination with ivonescimab. It is being tested to see if adding it to ivonescimab improves treatment outcomes for head and neck cancer.

Pembrolizumab is a medication used as the standard treatment for head and neck cancer. In this trial, it serves as the comparison treatment to see if the investigational medications work better.

Investigated diseases:

Squamous cell carcinoma of head and neck

Recurrent Squamous Cell Carcinoma of the Head and Neck – This is a type of cancer that comes back after initial treatment and originates in the flat, thin cells lining the moist surfaces of the head and neck region. These areas include the mouth, throat, voice box, nose, and sinuses. The disease occurs when squamous cells begin to grow abnormally and form tumors. When the cancer is recurrent, it means it has returned after a period of remission following previous treatment. The cancer may reappear in the same location as the original tumor or in nearby tissues.

Metastatic Squamous Cell Carcinoma of the Head and Neck – This is an advanced form of cancer where abnormal squamous cells from the head and neck region have spread to distant parts of the body. The cancer cells travel through the bloodstream or lymphatic system to form new tumors in organs far from the original site. Common areas where this cancer spreads include the lungs, liver, and bones. As the disease progresses, multiple organs may become affected by these secondary tumors. The metastatic form represents a more widespread stage of the disease compared to cancer that remains localized.

Trial ID:

2025-522996-27-00

Protocol code:

GORTEC 2024-04

Trial Phase:

Therapeutic confirmatory (Phase III)

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Study of ivonescimab alone or with ligufalimab versus pembrolizumab for patients with recurrent or metastatic head and neck squamous cell cancer

What is this study about?

Who Can Join the Study?

Who Cannot Join the Study?