The administration of first-line pembrolizumab monotherapy or combined chemotherapy has been shown to improve survival among patients with recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC). However, over 80% of the patients still experience disease progression within a year. Upon progression, treatment options are notably constrained, typically comprising methotrexate, docetaxel, and cetuximab. The median progression-free survivaland overall survival following chemotherapy, targeted therapy, or their combination are dismally low, ranging from 2-3 months and 6-8 months, respectively. The clinical trials CheckMate 141 and KEYNOTE 040 have led to the approval of Nivolumab and Pembrolizumab as second-line treatments for R/M HNSCC. Nevertheless, the response rates to immune monotherapy are limited, ranging from 10% to 35%. Even after receiving standard second-line immunotherapy, over 80% of patients encounter disease progression within 6 months, and more than 60% succumb to the disease within a year. Therefore, there is a dearth of a standardized treatment for R/M HNSCC after the failure of first- or second-line PD-1 (L1) inhibitors and/or platinum-based therapy
Who can participate
Age range
18 Years – 75 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
. Pathologically or cytologically confirmed R/M HNSCC (including oral, oropharyngeal, hypopharyngeal, and laryngeal sites); Recurrence that cannot be cured by local treatment, and previous treatment with PD-1 (L1) inhibitors and/or platinum-based chemotherapy has failed.
. At least one measurable lesion according to RECIST v1.1, excluding previously irradiated lesions unless clear progression occurred more than 3 months after the last radiotherapy;
. Known HPV p16 status of oropharyngeal cancer;
. Known PD-L1 expression status;
. ECOG performance status of 0-1;
. Expected survival ≥ 3 months;
. Adequate bone marrow function, defined as: Hb ≥ 9.0 g/dL (90 g/L); ANC ≥ 1,500/mcL (1.5 × 10\^9/L); PLT ≥ 100,000/mcL (100 × 10\^9/L) and no blood transfusion within 3 weeks or growth factor (G-CSF, EPO) therapy within 2 weeks prior to dosing;
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.
. Adequate liver function, defined as: TBIL ≤ 1.5× upper limit of normal (ULN); If no liver metastases, AST and ALT ≤ 2.5× ULN; if liver metastases are present, AST or ALT ≤ 3.0× ULN; ALP ≤ 1.5× ULN; if liver metastases ≤ 2× ULN; Serum albumin ≥ 30g/L;
Exclusion criteria
. Participants who have received treatment with cetuximab in the first line.
. Grade ≥2 peripheral neuropathy (according to CTCAE 5.0).
. Anticipated need for surgery or any other form of systemic or local anti-tumor therapy during the study, including maintenance therapy or radiotherapy for head and neck squamous cell carcinoma (excluding palliative treatment for non-target lesions).
. Received systemic chemotherapy within 3 weeks prior to first administration of study drug, received small molecule targeted therapy within 2 weeks prior to first administration or within 5 half-lives (whichever is longer), received anti-tumor biologic therapy, large molecule targeted therapy or immunotherapy within 4 weeks prior to first administration, or underwent major surgery (excluding minor surgery within 2 weeks with complete recovery); received radiotherapy within 14 days prior to first administration of study drug (excluding central nervous system radiotherapy which requires a washout period of ≥28 days).
. Known active central nervous system metastases and/or carcinomatous meningitis. Participants with treated brain metastases may participate if stable, without progressive or new neurological deficits, seizures, evidence of increased intracranial pressure, vomiting, or headaches.
. Lesions that are superficially ulcerated or have broken through at baseline.
. Residual toxicity from prior anti-tumor therapy (excluding alopecia, fatigue, and grade 2 hypothyroidism) or clinically significant laboratory abnormalities \> grade 1 (CTCAE v5.0).
. Pulmonary embolism or deep vein thrombosis within 3 months prior to first administration of study drug.