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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
316
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.
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.
Fudan University Shanghai Cancer Center
Shanghai, Shanghai Municipality, China
Progression Free Survival (PFS)
PFS assessed according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
Time frame: Expected 51 months following the First Subject First Visit (FSFV)
Objective Response Rate (ORR)
Disease Control Rate (DCR), Duration of Response (DoR), Time to Response (TTR), Overall Survival (OS)
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: Expected 51 months following the First Subject First Visit (FSFV)
Overall Survival (OS)
The time from randomization to death from any cause.
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Time frame: 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.
Time frame: Expected 51 months following the First Subject First Visit (FSFV)