Study Comparing Ivonescimab Alone or Ivonescimab in Combination With Ligufalimab Versus Pembroliz… (NCT07264075) | Clinical Trial Compass
RecruitingPhase 3
Study Comparing Ivonescimab Alone or Ivonescimab in Combination With Ligufalimab Versus Pembrolizumab for the Treatment of SCCHN
France780 participantsStarted 2026-05-05
Plain-language 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) 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
Who can participate
Age range
18 Years – 80 Years
Sex
ALL
See this in plain English?
AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.
Inclusion criteria
. 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.
Questions worth asking your doctor
Bring these to your next appointment. They're a starting point for a shared conversation — not a sign you qualify or a recommendation to enrol.
1Based on my diagnosis and history, is this trial worth exploring for me — or is there a standard treatment we should try first?
2What does this trial's phase tell us about how much is already known about its safety and benefit?
3What would taking part actually involve for me — visits, tests, time, and travel?
4What are the known and possible risks or side effects I should weigh, and how would they be monitored?
5If this trial isn't the right fit, what other options or trials would you suggest I look into?
Generated to help you prepare — always confirm anything about your own eligibility and care with the study team and your doctor.
Questions for the trial coordinator
The trial coordinator is the person who runs the study day to day. These cover the practical side — logistics, costs, and what taking part would actually mean for your life. The study team confirms whether you meet the criteria; these are questions to ask, not a sign you qualify.
1What does taking part actually involve week to week — how many visits, where, and how long does each one take?
2What costs are covered by the study, and what might I have to pay for myself, including travel, parking, or time off work?
3What happens during screening, and what happens if the study team confirms I don't meet the criteria after those tests?
4Who pays for the scans, blood work, and other tests the trial requires — the study, my insurance, or me?
5How will being in the trial affect my regular care, and will my own doctor stay informed and involved?
6Can I leave the trial at any point if I change my mind, and what would happen to my care if I do?
A starting point for the conversation — always confirm anything about your own eligibility, costs, and care with the study team and your doctor.
What they're measuring
1
Overall survival
Timeframe: From the date of randomization to the date of death from any cause up to 54 months
. 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).
Exclusion criteria
. 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.
. 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.