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This study is a randomized, active-controlled, open-label clinical trial for participants with newly diagnosed Stage III-IVb, resectable, locoregionally advanced head and neck squamous cell carcinoma (LA-HNSCC). The study consists of two experimental arms and one control arm. Participants in Experimental Arm A will receive two cycles of Toripalimab, albumin-bound paclitaxel, carboplatin, and cetuximab prior to surgery. Participants in Experimental Arm B will receive two cycles of Toripalimab, albumin-bound paclitaxel, and carboplatin before surgical intervention. Following the surgical procedure, individuals in both Experimental Arm A and B will continue to receive 15 cycles of Toripalimab. The Control Arm will undergo the current standard treatment without preoperative drug intervention. Postoperatively, participants will be administered postoperative radiotherapy or chemoradiotherapy based on their recurrence risk. The primary study hypotheses are that the treatments in the Experimental Arms will improve the 2-year event-free survival (EFS) rates compared to the standard control treatment.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Toripalimab + Chemotherapy + Cetuximab + SOC (Immunotherapy+ chemotherapy+targeted therapy, ICT) | Experimental | Participants will receive an intravenous (IV) infusion of Toripalimab 240mg on Day 1, Albumin-bound Paclitaxel 125mg/m^2 on Days 1 and 8, Carboplatin with an area under the curve (AUC) of 5 on Day 1, and Cetuximab 400mg/m^2 on Day 1, followed by Cetuximab 250mg/m^2 on Day 1 of each subsequent week. The treatment is given in 21-day cycles for a total of two cycles. Afterward, participants will proceed to the standard of care (SOC), which includes surgical intervention and postoperative radiotherapy. Following surgical resection, high-risk participants will receive standard radiotherapy plus Cisplatin 100 mg/m^2 via intravenous infusion on Day 1, every 3 weeks (Q3W) for three 21-day cycles. Low-risk participants will receive only standard radiotherapy. Subsequently, participants will receive Toripalimab 240mg every 21-day cycle for a total of 15 cycles. |
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| Toripalimab + Chemotherapy + SOC (Immunotherapy+ chemotherapy, IC) | Experimental | Participants will receive an intravenous (IV) infusion of Toripalimab 240mg on Day 1, Albumin-bound Paclitaxel 125mg/m^2 on Days 1 and 8, Carboplatin with an area under the curve (AUC) of 5 on Day 1. The treatment is given in 21-day cycles for a total of two cycles. Afterward, participants will proceed to the standard of care (SOC), which includes surgical intervention and postoperative radiotherapy. Following surgical resection, high-risk participants will receive standard radiotherapy plus Cisplatin 100 mg/m^2 via intravenous infusion on Day 1, every 3 weeks (Q3W) for three 21-day cycles. Low-risk participants will receive only standard radiotherapy. Subsequently, participants will receive Toripalimab 240mg every 21-day cycle for a total of 15 cycles. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Toripalimab | Biological | Specified dose on specified days |
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| Measure | Description | Time Frame |
|---|---|---|
| ICT vs Control: Two-Year Event-free Survival (EFS) rate | Two-Year Event-free Survival (EFS) rate defined as the proportion of participants who have not experienced any EFS events by the 2-year mark from randomization, out of all participants in the arm. EFS events: any progression of disease precluding surgery, progression or recurrence disease after surgery, death due to any cause, or occurrence of a second primary tumor. Participants who don't undergo surgery for reason other than progression will be considered to have an event at progression or death. EFS: The time from randomization, until the first documented occurrence of EFS event. Per protocol, Two-Year EFS rate in the ICT arm will be compared to the control arm as a pre-specified primary analysis of the Intent-To-Treat (ITT) population. | Up to ~72 months |
| IC vs Control: Two-Year EFS rate | Two-Year EFS rate defined as the proportion of participants who have not experienced any EFS events by the 2-year mark from randomization, out of all participants in the arm. EFS events: any progression of disease precluding surgery, progression or recurrence disease after surgery, death due to any cause, or occurrence of a second primary tumor. Participants who don't undergo surgery for reason other than progression will be considered to have an event at progression or death. EFS: The time from randomization, until the first documented occurrence of EFS event. Per protocol, Two-Year EFS rate in the IC arm will be compared to the control arm as a pre-specified primary analysis of the Intent-To-Treat (ITT) population. | Up to ~72 months |
| Measure | Description | Time Frame |
|---|---|---|
| ICT vs Control: Overall Survival (OS) | OS is the time from randomization to death due to any cause. Per protocol, OS in the ICT arm will be compared to the control arm as a pre-specified secondary analysis of the ITT population. | Up to ~96 months |
| IC vs Control: OS |
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Inclusion Criteria:
Histologically confirmed squamous cell carcinoma of the head and neck (excluding nasopharyngeal cancer);
Male or female, aged 18-75 years;
Clinical stage III-IVb (AJCC 8th edition TNM stage) and operable patients; if oropharyngeal squamous cell carcinoma (P16-), the stage is III-IVb; if oropharyngeal squamous cell carcinoma (P16+), the stage is III;
No prior antitumor therapy including radiotherapy, chemotherapy, immunotherapy or biological therapy for the current tumor;
Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1;
Life expectancy ≥ 6 months;
No obvious contraindications to immunotherapy, radiochemotherapy, or surgical treatment;
Willing to accept surgical treatment;
The level of main organ function meets the following criteria:
Women of childbearing potential must have a negative pregnancy test result (serum or urine), conducted within seven days prior to enrollment and agree to use effective contraception during the study period and for six months post last dose of anti-PD-1 antibody administration. Male subjects with female partners who are capable of conception must also utilize effective contraception throughout this study duration and for six months after their final dose anti-PD-1 antibody;
Willingness to participate in this study by signing an informed consent form, while exhibiting strong compliance and readiness to cooperate with follow-up procedures.
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Feng Liu, M.D. | Contact | 18917797783 | nuanliu@126.com |
| Name | Affiliation | Role |
|---|---|---|
| Yue He, M.D. | Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine | Principal Investigator |
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| No Neoadjuvant + SOC (Control) | Active Comparator | Participants will receive the standard of care (SOC) with no neoadjuvant prior to surgery. Following surgical resection, high-risk participants will receive standard radiotherapy plus Cisplatin 100 mg/m^2 via intravenous infusion on Day 1, every 3 weeks (Q3W) for three 21-day cycles. Low-risk participants will receive only standard radiotherapy. |
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| Cetuximab | Biological | Specified dose on specified days |
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| Albumin-Bound Paclitaxel | Drug | Specified dose on specified days |
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| Carboplatin | Drug | Specified dose on specified days |
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| Cisplatin | Drug | Specified dose on specified days |
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| Radiotherapy 60 Gray/day | Radiation | Low risk participants administered 2 Gray/day in 30 fractions. Administered using intensity modulated radiation therapy. |
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| Radiotherapy 66 Gray/day | Radiation | High risk participants administered 2 Gray/day in 33 fractions. Administered using intensity modulated radiation therapy. |
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| Radiotherapy 70 Gray/day | Radiation | Participants with gross residual disease administered 2 Gray/day in 35 fractions. Administered using intensity modulated radiation therapy. |
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OS is the time from randomization to death due to any cause. Per protocol, OS in the IC arm will be compared to the control arm as a pre-specified secondary analysis of the ITT population. |
| Up to ~96 months |
| ICT vs IC: Major Pathological Response (MPR) | The percentage of participants with a major pathological response (MPR) as assessed by the Central Pathologist at the time of definitive surgery. MPR is defined as ≤10% invasive squamous cell carcinoma within the resected primary tumor specimen and all the sampled regional lymph nodes. Per protocol, MPR in the ICT arm will be compared to the IC arm as a pre-specified secondary analysis of the ITT population. | Up to ~40 months |
| ICT vs IC: Pathological Complete Response (PCR) | he percentage of participants with a pathological complete response (PCR) as assessed by the central pathologist at the time of definitive surgery. PCR is defined as having no residual invasive squamous cell carcinoma within the resected primary tumor specimen and all sampled regional lymph nodes. Per protocol, PCR in the ICT arm will be compared to the IC arm as a pre-specified secondary analysis of the ITT population. | Up to ~40 months |
| ICT vs IC: Objective Response Rate (ORR) | According to Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), Objective Response Rate (ORR) assesses the proportion of subjects with complete response (CR) and partial response (PR). Per RECIST v1.1 criteria for target lesions and assessed by MRI or CT: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Per protocol, ORR in the ICT arm will be compared to the IC arm as a pre-specified secondary analysis of the ITT population. | Up to ~40 months |
| ICT vs Control: Three-Year EFS rate | Three-Year EFS rate defined as the proportion of participants who have not experienced any EFS events by the 3-year mark from randomization, out of all participants in the arm. EFS events: any progression of disease precluding surgery, progression or recurrence disease after surgery, death due to any cause, or occurrence of a second primary tumor. Participants who don't undergo surgery for reason other than progression will be considered to have an event at progression or death. EFS: The time from randomization, until the first documented occurrence of EFS event. Per protocol, Three-Year EFS rate in the ICT arm will be compared to the control arm as a pre-specified secondary analysis of the ITT population. | Up to ~84 months |
| ICT vs Control: Five-Year EFS rate | Five-Year EFS rate defined as the proportion of participants who have not experienced any EFS events by the 5-year mark from randomization, out of all participants in the arm. EFS events: any progression of disease precluding surgery, progression or recurrence disease after surgery, death due to any cause, or occurrence of a second primary tumor. Participants who don't undergo surgery for reason other than progression will be considered to have an event at progression or death. EFS: The time from randomization, until the first documented occurrence of EFS event. Per protocol, Five-Year EFS rate in the ICT arm will be compared to the control arm as a pre-specified secondary analysis of the ITT population. | Up to ~96 months |
| IC vs Control: Three-Year EFS rate | Three-Year EFS rate defined as the proportion of participants who have not experienced any EFS events by the 3-year mark from randomization, out of all participants in the arm. EFS events: any progression of disease precluding surgery, progression or recurrence disease after surgery, death due to any cause, or occurrence of a second primary tumor. Participants who don't undergo surgery for reason other than progression will be considered to have an event at progression or death. EFS: The time from randomization, until the first documented occurrence of EFS event. Per protocol, Three-Year EFS rate in the IC arm will be compared to the control arm as a pre-specified secondary analysis of the ITT population. | Up to ~84 months |
| IC vs Control: Five-Year EFS rate | Five-Year EFS rate defined as the proportion of participants who have not experienced any EFS events by the 5-year mark from randomization, out of all participants in the arm. EFS events: any progression of disease precluding surgery, progression or recurrence disease after surgery, death due to any cause, or occurrence of a second primary tumor. Participants who don't undergo surgery for reason other than progression will be considered to have an event at progression or death. EFS: The time from randomization, until the first documented occurrence of EFS event. Per protocol, Five-Year EFS rate in the IC arm will be compared to the control arm as a pre-specified secondary analysis of the ITT population. | Up to ~96 months |
| ICT vs IC: Two-Year EFS rate | Two-Year EFS rate defined as the proportion of participants who have not experienced any EFS events by the 2-year mark from randomization, out of all participants in the arm. EFS events: any progression of disease precluding surgery, progression or recurrence disease after surgery, death due to any cause, or occurrence of a second primary tumor. Participants who don't undergo surgery for reason other than progression will be considered to have an event at progression or death. EFS: The time from randomization, until the first documented occurrence of EFS event. Per protocol, Two-Year EFS rate in the ICT arm will be compared to the IC arm as a pre-specified secondary analysis of the ITT population. | Up to ~72 months |
| ICT vs IC: Three-Year EFS rate | Three-Year EFS rate defined as the proportion of participants who have not experienced any EFS events by the 3-year mark from randomization, out of all participants in the arm. EFS events: any progression of disease precluding surgery, progression or recurrence disease after surgery, death due to any cause, or occurrence of a second primary tumor. Participants who don't undergo surgery for reason other than progression will be considered to have an event at progression or death. EFS: The time from randomization, until the first documented occurrence of EFS event. Per protocol, Three-Year EFS rate in the ICT arm will be compared to the IC arm as a pre-specified secondary analysis of the ITT population. | Up to ~84 months |
| ICT vs IC: Five-Year EFS rate | Five-Year EFS rate defined as the proportion of participants who have not experienced any EFS events by the 5-year mark from randomization, out of all participants in the arm. EFS events: any progression of disease precluding surgery, progression or recurrence disease after surgery, death due to any cause, or occurrence of a second primary tumor. Participants who don't undergo surgery for reason other than progression will be considered to have an event at progression or death. EFS: The time from randomization, until the first documented occurrence of EFS event. Per protocol, Five-Year EFS rate in the ICT arm will be compared to the IC arm as a pre-specified secondary analysis of the ITT population. | Up to ~96 months |
| ICT vs IC vs Control: Locoregional recurrence-free survival (LRFS) rate | The Two-Year, Three-Year, and Five-Year LRFS rates refer to the proportions of participants who have not experienced locoregional recurrence and are still alive at 2, 3, and 5 years post-randomization, respectively, out of all participants in the arm. Per protocol, the LRFS rate will be compared between the ICT, IC, and Control arms. | Up to ~96 months |
| ICT vs IC vs Control: Distant Disease-free Survival (DDFS) rate | Two-Year, Three-Year, and Five-Year DDFS rates refer to the proportion of patients who have not experienced distant metastasis and are still alive at 2, 3, and 5 years post-randomization, out of all participants in the arm. Per protocol, the DDFS rate will be compared between the ICT, IC, and Control arms. | Up to ~96 months |
| ICT vs IC vs Control: Change From Baseline in Global Health Status/Quality of Life Scale (GHS/QoL) | Change from baseline in the combined score of global health status (GHS)/quality of life (QoL) using the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Core Questionnaire (EORTC QLQ-C30) items 29 and 30. Participant responses to questions regarding overall health/QoL will be scored on a 7-point scale (1=Very poor to 7=Excellent) with a higher score indicating better overall health status. | Up to ~96 months |
| ICT vs IC vs Control: Change From Baseline in Global Health Status/Physical Functioning Scales | Change from baseline in the combined score of physical functioning scale using the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Core Questionnaire (EORTC QLQ-C30) items 1 through 5. Participant responses to questions regarding their physical functioning will be scored on a 4-point scale (1=Not at All to 4=Very Much) with a higher score indicating worse physical functioning. | Up to ~96 months |
| ICT vs IC vs Control: Change from Baseline in Swallowing, Speech, and Pain Symptoms | Change from baseline in the combined score of swallowing, speech, and pain symptoms using the European Organization for Research and Treatment of Cancer Head and Neck Questionnaire (EORTC QLQ-H&N35) items 31-38, 46, and 53-54. Participant responses to questions regarding problems with swallowing, speech and pain in the mouth will be scored on a 4-point scale (1=Not at all to 4=Very much) with a higher score indicating more problems. | Up to ~96 months |
| ICT vs IC vs Control: Percentage of Participants Experiencing An Adverse Event (AEs) | Percentage of participants experiencing any sign, symptom, disease, or worsening of preexisting condition temporally associated with study therapy and irrespective of causality to study therapy. | Up to ~96 months |
| ICT vs IC: Percentage of Participants Discontinuing Study Drug Due to AEs | Percentage of participants discontinuing study drug due to an AE. | Up to ~48 months |
| ICT vs IC: OS | OS is the time from randomization to death due to any cause. Per protocol, OS in the ICT arm will be compared to the IC arm as a pre-specified secondary analysis of the ITT population. | Up to ~96 months |
| ID | Term |
|---|---|
| D000077195 | Squamous Cell Carcinoma of Head and Neck |
| C565324 | Parkinson Disease 4, Autosomal Dominant Lewy Body |
| ID | Term |
|---|---|
| D002294 | Carcinoma, Squamous Cell |
| D002277 | Carcinoma |
| D009375 | Neoplasms, Glandular and Epithelial |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D006258 | Head and Neck Neoplasms |
| D009371 | Neoplasms by Site |
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| ID | Term |
|---|---|
| C000656314 | toripalimab |
| C000711728 | spartalizumab |
| D000068818 | Cetuximab |
| D000068196 | Albumin-Bound Paclitaxel |
| D016190 | Carboplatin |
| D002945 | Cisplatin |
| ID | Term |
|---|---|
| D061067 | Antibodies, Monoclonal, Humanized |
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
| D007162 | Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |
| D017239 | Paclitaxel |
| D043823 | Taxoids |
| D043822 | Cyclodecanes |
| D003516 | Cycloparaffins |
| D006840 | Hydrocarbons, Alicyclic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D004224 | Diterpenes |
| D013729 | Terpenes |
| D000418 | Albumins |
| D056831 | Coordination Complexes |
| D017606 | Chlorine Compounds |
| D007287 | Inorganic Chemicals |
| D017672 | Nitrogen Compounds |
| D017671 | Platinum Compounds |
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