Squamous Cell Carcinoma Head and Neck Cancer (HNSCC)Phase 3ILLUMINENCT07264075
Study Comparing Ivonescimab Alone or Ivonescimab in Combination With Ligufalimab Versus Pembrolizumab for the Treatment of SCCHN
A Phase 3 study testing Ivonescimab 10 mg/kg, Ligufalimab and Pembrolizumab (KEYTRUDA ®) in people with Squamous Cell Carcinoma Head and Neck Cancer (HNSCC), run by Groupe Oncologie Radiotherapie Tete et Cou at 1 site in France.
Trial summary
This is a randomized, open-label, active-comparator-controlled, multi-regional, three-arm, phase 3 study comparing the efficacy and safety of ivonescimab in combination with ligufalimab to pembrolizumab and of ivonescimab alone to pembrolizumab as first-line treatment in patients with recurrent or metastatic (R/M)… Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Squamous Cell Carcinoma Head and Neck Cancer (HNSCC)
- What is being tested?
- Ivonescimab 10 mg/kg, Ligufalimab and Pembrolizumab (KEYTRUDA ®)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 780 participants
- Where
- 1 siteFrance
- Study dates
- 5 May 2026to May 2030
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patient capable of voluntary giving her/his written informed consent.
- Age ≥ 18 and < 80 years old at the time of enrolment.
- Eastern Cooperative Oncology Organization (ECOG) performance status score of 0 or 1.
- Expected survival ≥ 6 months at randomization.
- Patient is histologically and/or cytologically confirmed to have r/m HNSCC (according to the International Union Against Cancer and the American Joint Committee on Cancer 8th edition staging system) with a primary tumour initially or currently located in the oral cavity, oropharynx, hypopharynx, or larynx.
- HPV status test results based on tumour tissue samples must be obtained prior to randomization for patients with oropharyngeal cancer.
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- No prior systemic anti-tumour therapy for R/M HNSCC. Note: Patients who have previously received adjuvant/neoadjuvant chemotherapy with curative intent for non-metastatic disease, radiotherapy, or radical radiotherapy in combination with chemotherapy or cetuximab/EGFR based therapy for locally advanced disease are eligible for this study if disease progression occurs > 6 months after the end of the last treatment.
- At least one measurable lesion according to RECIST v1.1, or measurable lesion with clear radiographic progression after local therapy, and the lesion must be suitable for repeated accurate measurements (see Appendix 3).
- Tumours must be PD-L1 positive (CPS ≥ 1) as confirmed by CE-IVD immunohistochemistry assay based on local assessment with any assay validated for HNSCC in a laboratory compliant with National provisions. The measurement of PD-L1 protein expression can be performed based on archival tissue sample before the diagnosis of R/M tumour or based on tissue sample obtained after the diagnosis of a R/M tumour.
- Good organ function is determined by the following requirements:
- a.Haematology (satisfactory laboratory test results obtained during the screening period, and no blood components used within 14 days of cell growth factor supportive therapy): i.Absolute neutrophil value (ANC) ≥ 1.5×109/L (1,500/mm3) ii.Platelet count ≥ 100×109/L (100,000/mm3) iii.Haemoglobin ≥ 10 g/dL b.Kidneys: i.Calculated creatinine clearance (Appendix 4) ≥ 50 mL/min ii.Urine protein ≤ 2+ or 24 hours (h) urine protein quantification < 1.0 g c.Liver: i.Serum total bilirubin ≤ 1.5× upper limit of normal (ULN); for patients with liver metastases or confirmed/suspected Gilbert syndrome, ≤ 3 × ULN ii.AST and ALT ≤ 2.5×ULN; For patients with liver metastases, AST and ALT ≤ 5×ULN iii.Serum albumin ≥ 28 g/L d.Coagulation function: International normalized ratio (INR) and/or activated partial thromboplastin time (APTT) ≤ 1.5× ULN. This applies only to patients who are not on therapeutic anti- coagulation. Patients receiving therapeutic anti-coagulation should be on a stable dose.
Who cannot join
- Primary tumour site (any histology) of nasopharynx, nasal cavity, sinuses, salivary glands, thyroid or parathyroid glands, skin, or unknown primary site of tissue origin.
- Patient with malignancies other than HNSCC within 3 years prior to enrolment. Patients with other tumours that have been cured through local treatment, such as basal or cutaneous squamous cell carcinoma, superficial bladder cancer, cervical or breast carcinoma in situ, are not excluded.
- Concurrent enrolment in another clinical study, unless it is an observational, non-interventional clinical study or a follow-up period of an interventional study; Received study treatment within 4 weeks prior to randomization.
- Prior treatment with systemic anti-angiogenic drugs.
- Previous head and neck re-irradiation for recurrent/metastatic disease
- Prior immunotherapy, including immune checkpoint inhibitors (e.g., anti-PD-1/L1 antibody, anti- CTLA-4 antibody, anti-TIGIT antibody, anti-LAG3 antibody, anti-CD47, anti-SIRPα, etc.), immune checkpoint agonists (e.g., ICOS, CD40, CD137, GITR, OX40 antibodies, etc.), immune cell therapy, and any other treatment that targets tumour immunity including therapeutic tumour vaccine, and other adjuvant/neoadjuvant anti-PD-1 based therapy.
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- Patients with ulcers on the skin surface related to the current cancer during the screening period, superficial or protruding skin lesions with excessive surface tension and a greater risk of ulceration, or other patients with a greater risk of ulceration as assessed by the investigator. Patients with recent tracheostomy involving the tumour which are at risk of bleeding.
- Imaging during the screening period shows that the tumour invades/infiltrates the surrounding important organs (such as trachea, oesophagus, and based on investigator assessment ofbleeding risk) and/or large blood vessels in the neck (such as subclavian artery, common internal and/or external carotid artery, etc.) or if the investigator judges that entering the study might cause a potential risk of bleeding.
- Presence of brainstem, meningeal metastases, spinal cord metastases or compression, or leptomeningeal disease.
- Received curative head and neck radiotherapy within 6 months prior to randomization. Palliative local treatment for non-head and neck areas carried out within 3 weeks before randomization; Received non-specific immunomodulatory therapy (such as interleukin, interferon, thymus peptide, tumour necrosis factor, etc.) within 2 weeks prior to randomization, excluding IL-11 for the treatment of thrombocytopenia.
- Presence of active autoimmune disease requiring systemic therapy (e.g., treatment with disease-modifying drugs, corticosteroids, immunosuppressants) within 2 years prior to randomization. Alternative therapies (e.g., thyroxine, insulin, or those targeting the adrenal glands or pituitary) and physiologic corticosteroid replacement therapy for pituitary insufficiency are not considered systemic treatment.
- History of immunodeficiency; Those who have history of positive test for HIV antibodies; Current long-term use of systemic corticosteroids or other immunosuppressants is excluded.
- Previous or current non-infectious pneumonitis/interstitial lung disease requiring systemic glucocorticoid therapy, or current presence of lung diseases including but not limited to the following: pneumoconiosis, silicosis, drug-related pneumonia, pulmonary diseases with severe impairment of lung function, etc.
- Severe infection within 4 weeks prior to randomization, including but not limited to comorbidities requiring hospitalization, sepsis, or severe pneumonia; Active non-severe infection that has received systemic anti-infective therapy within 2 weeks prior to randomization.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
France1 site, 1 recruiting
- Recruiting
Centre Guillaume Le Conquerant
Le Havre, 76600
Laurent MARTIN, Dr, +33235136613, l.martin@cglc.fr
About this study
Official title: A Randomized, Open-label, Multicenter, Phase 3 Trial of Ivonescimab Alone or With Ligufalimab Versus Pembrolizumab in First-line Recurrent and/or Metastatic Head and Neck Squamous Cell Carcinoma (HNSCC)
This is a randomized, open-label, active-comparator-controlled, multi-regional, three-arm, phase 3 study comparing the efficacy and safety of ivonescimab in combination with ligufalimab to pembrolizumab and of ivonescimab alone to pembrolizumab as first-line treatment in patients with recurrent or metastatic (R/M) PD-L1-positive squamous cell carcinoma of the head and neck (HNSCC).
The objective of this study is to improve first-line survival in patients with recurrent or metastatic PD-L1-positive HNSCC (CPS ≥ 1). Overall survival (OS) was chosen as the primary endpoint.
Read more
Patients will receive the following treatment regimens in accordance with the study treatment plan until disease progression, death, intolerable toxicity, or the occurrence of another protocol-specified treatment discontinuation criterion, whichever occurs first.
- ARM A: Ivonescimab (10 mg/kg iv, 60 min ± 10 min infusion, Q3W)
- ARM B: Ivonescimab (10 mg/kg iv, 60 min ± 10 min infusion, Q3W), and ligufalimab (45 mg/kg iv, 120 min ± 15 min infusion, Q3W).
- ARM C (control arm): Pembrolizumab (200 mg iv, 60 min ± 10 min infusion, Q3W). The total duration of treatment is up to 24 months
- Being tested
- Ivonescimab 10 mg/kg, Ligufalimab, Pembrolizumab (KEYTRUDA ®)
- Keywords
- first-line recurrent and/or metastatic
- Medical subject headings
- Head and Neck Neoplasms, Squamous Cell Carcinoma of Head and Neck
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ivonescimab 10 mg/kgDrug
Also called AK112
Ivonescimab is a humanized immunoglobulin (Ig) G1 monoclonal antibody (mAb) being investigated as a cancer immunotherapy agent. Ivonescimab binds to human VEGF-A which is involved in tumor angiogenesis, and to human PD-1 that is a cell surface receptor expressed primarily on activated T cells and acts to inhibit T cell activation.
LigufalimabDrug
Also called AK117
AK117 is a humanized IgG4 mAb being investigated as a cancer immunotherapy agent
Pembrolizumab (KEYTRUDA ®)Drug
Also called Keytruda
Pembrolizumab is a humanized monoclonal antibody (IgG4 kappa isotype with stabilizing sequence alteration in the Fc region) against PD-1 (programmed cell death-1), produced in Chinese hamster ovary cells by recombinant DNA technology.
| Study group | Role | What they receive |
|---|---|---|
| Bras A: Ivonescimab | Experimental | Ivonescimab (10 mg/kg iv, 60 min ± 10 min infusion, Q3W) Receives: Drug: Ivonescimab 10 mg/kg |
| Bras B: Ivonescimab - Ligufalimab | Experimental | Ivonescimab (10 mg/kg iv, 60 min ± 10 min infusion, Q3W), and ligufalimab (45 mg/kg iv, 120 min ± 15 min infusion, Q3W). Receives: Drug: Ivonescimab 10 mg/kg; Drug: Ligufalimab |
| Bras C: Pembrolizumab | Active comparator | Pembrolizumab (200 mg iv, 60 min ± 10 min infusion, Q3W). Receives: Drug: Pembrolizumab (KEYTRUDA ®) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall survival
the time from the date of randomization to the date of death from any cause. Patients still alive at the time of analysis will be censored at the date of their last known alive date
Measured: From the date of randomization to the date of death from any cause up to 54 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Dec 2025
- Study start5 May 2026
- Primary completionMay 2030 (estimated)
- Study completionMay 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Squamous Cell Carcinoma Head and Neck Cancer (HNSCC)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 780 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Groupe Oncologie Radiotherapie Tete et Cou
- Sponsor type
- University, hospital or other
- Collaborators
- Akeso Biopharma Co., Ltd., Summit Therapeutics
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07264075
- Sponsor's protocol ID
- GORTEC 2024-04
- Other IDs
- 2025-522996-27-00, 2025
- Acronym
- ILLUMINE
- Status last verified
- May 2026
- First submitted
- 29 Sep 2025
- Last updated
- 20 May 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: The study will be conducted in Europe and China, with GORTEC as the sponsor. A single, secure database will be used, and pseudonymized participant data will be shared among the partners.
Study at a glance
From the registry record, last updated by the sponsor on 20 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Open-label, Multicenter, Phase 3 Trial of Ivonescimab Alone or With Ligufalimab Versus Pembrolizumab in First-line Recurrent and/or Metastatic Head and Neck Squamous Cell Carcinoma (HNSCC)
- ClinicalTrials.gov ID
- NCT07264075
- Acronym / sponsor ID
- ILLUMINE / GORTEC 2024-04
- Keywords
- first-line recurrent and/or metastatic
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 780 participants (estimated)
- Lead sponsor
- Groupe Oncologie Radiotherapie Tete et CouUniversity, hospital or other
- Collaborators
- Akeso Biopharma Co., Ltd., Summit Therapeutics
- Study start
- 5 May 2026 (actual)
- Primary completion
- May 2030 (estimated)
- Study completion
- May 2030 (estimated)
- First posted
- 4 Dec 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a randomized, open-label, active-comparator-controlled, multi-regional, three-arm, phase 3 study comparing the efficacy and safety of ivonescimab in combination with ligufalimab to pembrolizumab and of ivonescimab alone to pembrolizumab as first-line treatment in patients with recurrent or metastatic (R/M) PD-L1-positive squamous cell carcinoma of the head and neck (HNSCC).
The objective of this study is to improve first-line survival in patients with recurrent or metastatic PD-L1-positive HNSCC (CPS ≥ 1). Overall survival (OS) was chosen as the primary endpoint.
Patients will receive the following treatment regimens in accordance with the study treatment plan until disease progression, death, intolerable toxicity, or the occurrence of another protocol-specified treatment discontinuation criterion, whichever occurs first.
- ARM A: Ivonescimab (10 mg/kg iv, 60 min ± 10 min infusion, Q3W)
- ARM B: Ivonescimab (10 mg/kg iv, 60 min ± 10 min infusion, Q3W), and ligufalimab (45 mg/kg iv, 120 min ± 15 min infusion, Q3W).
- ARM C (control arm): Pembrolizumab (200 mg iv, 60 min ± 10 min infusion, Q3W). The total duration of treatment is up to 24 months
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Bras A: Ivonescimab | Experimental | Drug: Ivonescimab 10 mg/kgIvonescimab (10 mg/kg iv, 60 min ± 10 min infusion, Q3W) |
| Bras B: Ivonescimab - Ligufalimab | Experimental | Drug: Ivonescimab 10 mg/kg, Drug: LigufalimabIvonescimab (10 mg/kg iv, 60 min ± 10 min infusion, Q3W), and ligufalimab (45 mg/kg iv, 120 min ± 15 min infusion, Q3W). |
| Bras C: Pembrolizumab | Active comparator | Drug: Pembrolizumab (KEYTRUDA ®)Pembrolizumab (200 mg iv, 60 min ± 10 min infusion, Q3W). |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Patient capable of voluntary giving her/his written informed consent.
- Age ≥ 18 and < 80 years old at the time of enrolment.
- Eastern Cooperative Oncology Organization (ECOG) performance status score of 0 or 1.
- Expected survival ≥ 6 months at randomization.
- Patient is histologically and/or cytologically confirmed to have r/m HNSCC (according to the International Union Against Cancer and the American Joint Committee on Cancer 8th edition staging system) with a primary tumour initially or currently located in the oral cavity, oropharynx, hypopharynx, or larynx.
Key exclusion criteria (14 listed)
- Primary tumour site (any histology) of nasopharynx, nasal cavity, sinuses, salivary glands, thyroid or parathyroid glands, skin, or unknown primary site of tissue origin.
- Patient with malignancies other than HNSCC within 3 years prior to enrolment. Patients with other tumours that have been cured through local treatment, such as basal or cutaneous squamous cell carcinoma, superficial bladder cancer, cervical or breast carcinoma in situ, are not excluded.
- Concurrent enrolment in another clinical study, unless it is an observational, non-interventional clinical study or a follow-up period of an interventional study; Received study treatment within 4 weeks prior to randomization.
- Prior treatment with systemic anti-angiogenic drugs.
- Previous head and neck re-irradiation for recurrent/metastatic disease
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Ivonescimab 10 mg/kgAlso: AK112Ivonescimab is a humanized immunoglobulin (Ig) G1 monoclonal antibody (mAb) being investigated as a cancer immunotherapy agent. Ivonescimab binds to human VEGF-A which is involved in tumor angiogenesis, and to human PD-1 that is a cell surface receptor expressed primarily on activated T cells and acts to inhibit T cell activation. | Drug | Bras A: Ivonescimab, Bras B: Ivonescimab - Ligufalimab |
| LigufalimabAlso: AK117AK117 is a humanized IgG4 mAb being investigated as a cancer immunotherapy agent | Drug | Bras B: Ivonescimab - Ligufalimab |
| Pembrolizumab (KEYTRUDA ®)Also: KeytrudaPembrolizumab is a humanized monoclonal antibody (IgG4 kappa isotype with stabilizing sequence alteration in the Fc region) against PD-1 (programmed cell death-1), produced in Chinese hamster ovary cells by recombinant DNA technology. | Drug | Bras C: Pembrolizumab |
Primary outcome
Overall survival
Time frame: From the date of randomization to the date of death from any cause up to 54 months
the time from the date of randomization to the date of death from any cause. Patients still alive at the time of analysis will be censored at the date of their last known alive date
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 May 2026.
- Individual participant dataSharing planned: Yes. The study will be conducted in Europe and China, with GORTEC as the sponsor. A single, secure database will be used, and pseudonymized participant data will be shared among the partners.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Ivonescimab 10 mg/kg, Ligufalimab and Pembrolizumab (KEYTRUDA ®) in people with Squamous Cell Carcinoma Head and Neck Cancer (HNSCC), run by Groupe Oncologie Radiotherapie Tete et Cou at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 20 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall survival (time frame: From the date of randomization to the date of death from any cause up to 54 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 May 2026.