Informations générales (source: ClinicalTrials.gov)
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)
Interventional
Phase 3
Groupe Oncologie Radiotherapie Tete et Cou (Voir sur ClinicalTrials)
mai 2026
mai 2030
21 mai 2026
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
Etablissements
| Les établissements d'Île-de-France ayant mis à jour leurs données Origine et niveau de fiabilité des données | |||||
|---|---|---|---|---|---|
| CLCC INSTITUT GUSTAVE ROUSSY | L�a LORIGUET | 09/06/2026 12:45:07 | Contacter | ||
| Les établissements hors Île-de-France dont les données sont issues de ClinicalTrials.gov Origine et niveau de fiabilité des données | |||||
| Centre Guillaume Le Conquerant - 76600 - Le Havre - France | Laurent MARTIN, Dr | Contact (sur clinicalTrials) | |||
Critères
Tous
1. Patient capable of voluntary giving her/his written informed consent.
2. Age ≥ 18 and < 80 years old at the time of enrolment.
3. Eastern Cooperative Oncology Organization (ECOG) performance status score of 0 or 1.
4. Expected survival ≥ 6 months at randomization.
5. 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.
6. HPV status test results based on tumour tissue samples must be obtained prior to
randomization for patients with oropharyngeal cancer.
7. 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.
8. 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).
9. 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.
10. 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.
Exclusion Criteria:
1. Primary tumour site (any histology) of nasopharynx, nasal cavity, sinuses, salivary
glands, thyroid or parathyroid glands, skin, or unknown primary site of tissue
origin.
2. 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.
3. 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.
4. Prior treatment with systemic anti-angiogenic drugs.
5. Previous head and neck re-irradiation for recurrent/metastatic disease
6. 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.
7. 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.
8. 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.
9. Presence of brainstem, meningeal metastases, spinal cord metastases or compression,
or leptomeningeal disease.
10. 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.
11. 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.
12. 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.
13. 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.
14. 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.