Squamous Cell Carcinoma of Head and Neck
Conditions
Brief summary
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.
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.
Interventions
DRUGcetuximab+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.
DRUGPD-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.
Sponsors
Ji Dongmei
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival (PFS) | Expected 51 months following the First Subject First Visit (FSFV) | PFS assessed according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) | Expected 51 months following the First Subject First Visit (FSFV) | Disease Control Rate (DCR), Duration of Response (DoR), Time to Response (TTR), Overall Survival (OS) |
| Disease Control Rate (DCR) | Expected 51 months following the First Subject First Visit (FSFV) | 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. |
| Duration of Response (DoR) | Expected 51 months following the First Subject First Visit (FSFV) | 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. |
| Time to Response (TTR) | Expected 51 months following the First Subject First Visit (FSFV) | 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. |
| Overall Survival (OS) | Expected 51 months following the First Subject First Visit (FSFV) | The time from randomization to death from any cause. |
| Safety Endpoints | Expected 51 months following the First Subject First Visit (FSFV) | Incidence and severity of adverse events (AEs) and serious adverse events (SAE), including abnormalities in vital signs, electrocardiograms, and laboratory tests. |
Countries
China
Contacts
CONTACTDongmei Ji Doctor
Outcome results
None listed