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.

Study Overview

• Status: Not yet recruiting
• Conditions: Squamous Cell Carcinoma of Head and Neck
• Intervention / Treatment: Drug: cetuximab+PD-1 mAb(Pembrolizumab/Finotonlimab)+chemotherapy; Drug: PD-1 mAb (Pembrolizumab/Finotonlimab) + chemothearpy

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 316
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Dongmei Ji Doctor; Phone Number: +86 13564183928; Email: jidm2025@163.com

Study Locations

• China
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China
      • Fudan University Shanghai Cancer Center
      • Contact: Dongmei Ji Doctor; Phone Number: +86 13564183928; Email: jidm2025@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental Group; cetuximab + PD-1 mAb + chemotherapy	Drug: cetuximab+PD-1 mAb(Pembrolizumab/Finotonlimab)+chemotherapy; Cetuximab: 400 mg/m2 initial dose followed by 250 mg/m2 (weekly), iv, until disease progression, intolerable toxicity, or the subject voluntarily requests to discontinue the trial treatment. Pembrolizumab or Finotonlimab：200mg, iv, administered on Day 1, Q3W, until disease progression, intolerable toxicity, or the subject voluntarily requests to discontinue the trial treatment. Nab-paclitaxel: 260 mg/m², iv over 30 minutes, administered on Day 1, Q3W, for a maximum of 6 cycles. Cisplatin: 75 mg/m², iv (hydration), administered on Day 1, repeated Q3W (if cisplatin-related non-hematological toxicity occurs, treatment may switch to carboplatin area under the curve(AUC)=5; if cisplatin intolerant patients, carboplatin(AUC=5) could be used), for a maximum of 6 cycles.
Active Comparator: Control Group; PD-1 mAb + chemotherapy	Drug: PD-1 mAb (Pembrolizumab/Finotonlimab) + chemothearpy; Pembrolizumab or Finotonlimab：200mg, iv, administered on Day 1, Q3W, until disease progression, intolerable toxicity, or the subject voluntarily requests to discontinue the trial treatment. Nab-paclitaxel: 260 mg/m², iv over 30 minutes, administered on Day 1, Q3W, for a maximum of 6 cycles. Cisplatin: 75 mg/m², iv (hydration), administered on Day 1, repeated Q3W (if cisplatin-related non-hematological toxicity occurs, treatment may switch to carboplatin area under the curve(AUC)=5; if cisplatin intolerant patients, carboplatin(AUC=5) could be used), for a maximum of 6 cycles.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival (PFS)	PFS assessed according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1	Expected 51 months following the First Subject First Visit (FSFV)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR)	Disease Control Rate (DCR), Duration of Response (DoR), Time to Response (TTR), Overall Survival (OS)	Expected 51 months following the First Subject First Visit (FSFV)
Disease Control Rate (DCR)	The disease control rate (DCR) is defined as the proportion of subjects in the full analysis set (FAS) whose best overall response is either complete response (CR), partial response (PR), or stable disease (SD) based on investigator assessment using RECIST v1.1. Subjects with SD must have maintained SD for at least 6 weeks from the first dose to be counted as disease control.	Expected 51 months following the First Subject First Visit (FSFV)
Duration of Response (DoR)	The time from the first documented evidence of objective response (CR or PR) to the first documented disease progression or death from any cause, whichever occurred first.	Expected 51 months following the First Subject First Visit (FSFV)
Time to Response (TTR)	The time from the date of randomization to the date of the first documented objective response (complete response [CR] or partial response [PR]) in patients who ultimately achieve a response.	Expected 51 months following the First Subject First Visit (FSFV)
Overall Survival (OS)	The time from randomization to death from any cause.	Expected 51 months following the First Subject First Visit (FSFV)
Safety Endpoints	Incidence and severity of adverse events (AEs) and serious adverse events (SAE), including abnormalities in vital signs, electrocardiograms, and laboratory tests.	Expected 51 months following the First Subject First Visit (FSFV)

Collaborators and Investigators

• Sponsor: Ji Dongmei

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2026
• Primary Completion (Estimated): September 30, 2030
• Study Completion (Estimated): September 30, 2030

Study Registration Dates

• First Submitted: March 24, 2026
• First Submitted That Met QC Criteria: March 28, 2026
• First Posted (Actual): April 3, 2026

Study Record Updates

• Last Update Posted (Actual): April 3, 2026
• Last Update Submitted That Met QC Criteria: March 28, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Head and Neck Neoplasms; Neoplasms, Glandular and Epithelial; Carcinoma; Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck; pembrolizumab
• Other Study ID Numbers: FUSCC-HN-003

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No