Cetuximab Combined With Pembrolizumab or Finotonlimab and Chemotherapy in R/M HNSCC

Cetuximab Combined With Pembrolizumab or Finotonlimab and Chemotherapy in R/M HNSCC: an Open-label, Randomized, Prospective, Multicenter Phase III Trial

This is an open-label, randomized, prospective, multicenter phase III trial to evaluate the efficacy and safety of the combination therapy of cetuximab with either pembrolizumab or finotonlimab, alongside chemotherapy, as a first-line treatment, compared with pembrolizumab or finotonlimab with chemotherapy for R/M HNSCC.

Patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) who are not candidates for curative-intent therapies have a poor prognosis.

Currently, the standard treatment involves a combination of cetuximab with chemotherapy or a PD-1 inhibitor-based regimen.

This study is an open-label, randomized, prospective, multicenter phase III trial requiring a total of 316 R/M HNSCC patients. Participants will be randomized into either the experimental group or the control group. The stratification factors include the choice of PD-1 inhibitor (pembrolizumab versus finotonlimab) and the primary tumor site (oral cavity, hypopharynx, or others).

Patients in the experimental group will receive cetuximab along with either pembrolizumab or finotonlimab, nab-paclitaxel, and cisplatin. Those in the control group will receive either pembrolizumab or finotonlimab, nab-paclitaxel, and cisplatin.

Inclusion Criteria:

1. Age 18-70 years;
2. ECOG Performance Status 0 or 1;
3. Histologically confirmed diagnosis of head and neck squamous cell carcinoma;
4. Subjects with distant metastasis or local recurrence not suitable for curative treatment; local recurrence patients must have previously received radiotherapy (postoperative or radical);
5. No prior systemic chemotherapy; subjects who have ceased chemotherapy for locally advanced disease as part of multidisciplinary treatment for more than 6 months may be enrolled;
6. At least one measurable lesion available for evaluation by enhanced CT or MRI according to RECIST 1.1;
7. Adequate organ function:
8. Estimated survival greater than 3 months;
9. Voluntary signing of informed consent form, with good compliance expected, and ability to follow up as required by the protocol.

Exclusion Criteria:

1. Nasopharyngeal carcinoma；
2. Known allergic reaction against any of the components of the trial treatment;
3. a. Previous treatment with immune checkpoint inhibitors (ICIs) (Prior receipt of ICIs is allowed if they were given as part of curative-intent neoadjuvant therapy, with more than 6 months between the last dose and disease recurrence, or as adjuvant ICI monotherapy that achieved disease control for over 6 months); b. Previous treatment with cetuximab (Prior receipt of cetuximab is allowed if they were given as part of curative-intent therapy, with more than 6 months between the last dose and disease recurrence); c．Previous treatment with chemotherapy (Prior receipt of chemotherapy is allowed if they were given as part of curative-intent neoadjuvant and adjuvant therapy, with more than 6 months between the last dose and disease recurrence) The end date of the therapies mentioned above is the date of the last administration.
4. Clinically significant heart disease, including severe heart failure: NYHA heart failure class III~IV, ischemic heart disease (e.g., myocardial infarction or angina), acute myocardial infarction or congestive heart failure or QTc interval greater than 500 ms within the last 6 months;
5. Undergoing or expected to undergo secondary or higher surgeries within three weeks prior to the first dose;
6. Autoimmune diseases requiring treatment or a history of syndromes requiring systemic use of corticosteroids or immunosuppressants, such as pituitary inflammation, pneumonia, colitis, hepatitis, nephritis, hyperthyroidism, hypothyroidism, etc.;
7. Other serious uncontrolled concomitant diseases affecting protocol compliance or result interfere, including uncontrolled diabetes or pulmonary diseases (interstitial pneumonia, obstructive lung disease, and symptomatic bronchospasm history);
8. Known active central nervous system metastasis and/or leptomeningeal disease; Note: Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging (using the identical imaging modality for each assessment, either MRI or CT scan) for at least 4 weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment. This exception does not include carcinomatous meningitis which is excluded regardless of clinical stability.
9. Hepatitis B (HBV) (HBsAg positive and HBV-DNA≥ 103 IU/ml), hepatitis C (HCV) infection (HCV antibody positive and detectable HCV-RNA); and other acquired or congenital immunodeficiency diseases, including but not limited to HIV infection;
10. Pregnant or breastfeeding women, or women planning to conceive during treatment and within 6 months after the last dose of study medication. Fertile women and sexually active men unwilling to use highly effective contraception during the study and for 6 months afterward.
11. Severe active infections;
12. Severe neurological or psychiatric history, including dementia or epilepsy;
13. Drug abuse, medical, psychological, or social conditions that may interfere with the subject's participation in the trial or the assessment of results;
14. Other reasons deemed unsuitable for enrollment by the investigator.