Adebrelimab Combined With Carboplatin and Albumin-bound Taxanol in the Treatment of Resectable Locally Advanced Oral Squamous Cell Carcinoma Cardiac, Randomized, Phase II Exploratory Study
Phase: PHASE2
Conditions: Oral Squamous Cell Carcinoma (OSCC), Neoadjuvant Chemoimmunotherapy
Sponsor: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University

 1 / 37 
 
Clinical study protocol 
 
Project Name: A single-center, randomized, phase II exploratory 
study of adebelimab combined with carboplatin and nab-binding 
squamous alcohol in the treatment of resectable locally advanced oral 
squamous cell carcinoma 
Sponsor: Sun Yat-sen Memorial Hospital, Sun Yat-sen University 
Version number: V4.0 
Version date: 2025.0721 
 
 
 
 
Plan signing confirmation: 
 
 
 
Statement of Compliance 
In compliance with the provisions of the Good Practice for Drug Clinical Trials and the 
Administrative Measures for Conducting Investigator-initiated Clinical Research in Medical and 
Health Institutions (Trial) and the Declaration of Helsinki, participants must be trained to carry out 
the study after obtaining written approval from the ethics committee and the written informed consent 
of the subjects. 
 

 2 / 37 
 
1. Summary of the plan 
 
Neoadjuvant immunochemotherapy can effectively improve the postoperative 
pathological complete response rate, improve patient survival, and reduce the risk of 
recurrence in oral squamous cell carcinoma (OSCC). Programmed death ligand-1 (PD-
L1) plays a role in inhibiting the cancer-immune cycle by binding to negative regulators 
of T cell activation such as PD-1 and B7.1, and has achieved good efficacy in lung 
cancer, liver cancer and other cancers. Previous studies have shown that three cycles of 
PD-L1 inhibitor combined with chemotherapy have satisfactory efficacy and safety in 
locally advanced oral squamous cell carcinoma. However, in the course of three cycles 
of medication, due to the accumulation of drug toxic effects, the patient's tolerance to 
adverse reactions decreases, which increases the risk of serious adverse events and 
increases the psychological pressure of the patient. On this basis, this study aims to 
explore the efficacy of two cycles of adebelimab (PD-L1 inhibitor) combined with 
chemotherapy in locally advanced oral squamous cell carcinoma, and explore whether 
it can shorten the treatment time while achieving the equivalent of three cycles of 
efficacy and reducing the risk of serious adverse eventsTo further verify the efficacy 
and safety of PD-L1 inhibitors combined with chemotherapy in the treatment of locally 
advanced oral squamous cell carcinoma. In this study, the postoperative pathological 
complete response (PCR) rate was used as the primary outcome indicator, and the tumor 
objective response (ORR) rate, major pathological response (MPR) rate, 2-year disease-
free survival (EFS) rate, and 2-year and 5-year overall survival (OS) rates were used as 
secondary outcome measures to evaluate the efficacy and long-term survival impact.  
 
2. Introduction 
2.1 Research theoretical basis/background 
According to the latest data from the International Agency for Research on Cancer, 
the global incidence of head and neck cancer in 2022 ranks among the top ten new 
cancer incidences in the world [1]. Among them, the treatment guidelines for locally 
advanced head and neck squamous cell carcinoma (HNSCC) are risk-adapted adjuvant 

 3 / 37 
 
radiotherapy with or without platinum-based chemotherapy, or definitive concurrent 
chemoradiotherapy after surgical resection. However, despite aggressive combination 
therapy, patients with locally advanced HNSCC remain at high risk of recurrence, 
distant metastasis, and death [2,3]. With the proposal of the treatment concept of 
preoperative induction chemotherapy, clinical studies have shown that patients who 
achieve tumor remission after preoperative induction chemotherapy have a higher 
survival rate and lower risk of distant metastasis, but the complete response rate of 
tumor pathology after surgery is low, and the effect has not been satisfactory [4]. 
Tumor immunotherapy provides the possibility to solve the above dilemma. At 
present, immune checkpoint inhibitors (ICIs) are widely used in oral squamous cell 
carcinoma (OSCC). A clinical study (KEYNOTE-048) showed that pembrolizumab 
(PD-1) combined with chemotherapy significantly improved the survival of patients 
with recurrent or metastatic oral squamous cell carcinoma [5], and has now become the 
first-line treatment option according to NCCN guidelines. Meanwhile, in a 
retrospective study by Li et al. [6], neoadjuvant chemoimmunotherapy (NACL) showed 
safe and encouraging efficacy in patients with locally advanced resectable OSCC. 
Among the 104 patients who received NACI, the pathological complete response (PCR) 
rate was 47.1%, the major pathological response (MPR) rate was 65.4%, and the 
expected 3-year disease-free survival (DFS) rate and overall survival (Overall survival, 
OS) rates of 89.0% and 91.3%, suggesting that NACI can effectively improve the 
postoperative pathological remission rate and improve the prognosis of patients. 
Programmed death ligand-1 (PD-L1) plays a role in inhibiting the cancer-immune 
cycle by binding to negative regulators of T cell activation, such as PD-1 and B7.1 [7]. 
In a meta-analysis [8], the overall average incidence of grade 3 or higher adverse events 
was higher with PD-1 inhibitors than with PD-L1 inhibitors (OR, 1.58; 95% CI, 1.00-
2.54), which may be due to the fact that PD-L1 inhibitors bind PD-L1 on the surface of 
tumor cells and antigen-presenting cells, but retain the normal function of PD-L2, 
thereby reducing the risk of potential autoimmune reactions and adverse events [9,10]. 
Therefore, PD-L1 inhibitors may have more therapeutic potential than PD-1 inhibitors. 

 4 / 37 
 
Currently, PD-L1 inhibitors are mostly used in lung cancer, liver cancer, and triple-
negative breast cancer [11-13]. Adebrelimab, a human-derived monoclonal antibody 
against PD-L1, significantly improved median overall survival in the adebrelimab arm 
in a phase 3 clinical trial in combination with chemotherapy for small cell lung cancer 
[14] (median 15.3 months [95% CI; 13.2-17.5]）。 However, there is a lack of research 
on its application in oral squamous cell carcinoma, and the existing phase I clinical 
studies have confirmed its therapeutic safety and tumor activity [15]. In addition, 
previous studies have shown that in 28 patients with locally advanced oral squamous 
cell carcinoma who received three cycles of PD-L1 inhibitor (adebelimab) combined 
with chemotherapy, the tumor objective response (ORR) rate was 60.7% (95% CI, 
40.58%-78.50%) and the complete pathologic response (PCR) rate was 35.7% (95% CI, 
18.64%-55.93%)), showing satisfactory efficacy, confirming that the PD-L1 inhibitor 
(adebelimab) can effectively increase the PCR rate. However, in the course of three 
cycles of medication, due to the accumulation of drug toxic effects, the patient's 
tolerance to adverse reactions decreases, which increases the risk of serious adverse 
events and increases the psychological pressure of the patient. On this basis, this study 
aims to explore the efficacy of two cycles of adebelimab (PD-L1 inhibitor) combined 
with chemotherapy in locally advanced oral squamous cell carcinoma, explore whether 
it can shorten the treatment time while achieving the same efficacy as three cycles, 
reduce the risk of serious adverse events, and further verify the efficacy and safety of 
PD-L1 inhibitor combined with chemotherapy in the treatment of locally advanced oral 
squamous cell carcinoma.  
2.2 Risk/benefit assessment 
2.2.1 Known potential risks 
The potential risks of this study mainly include adverse reactions after the use of PD-
L1 inhibitors, the superprogress of tumor treatment caused by the study protocol itself, 
and the risk of sudden accidents in the study. 
2.2.2 Known potential benefits 
The potential benefits of the subjects in this study are: the treatment effect of the study 

 5 / 37 
 
regimen has enabled the subjects to achieve complete or partial remission of the tumor; 
Subjects who accept the research program can receive a certain drug donation policy 
and obtain certain financial assistance; Subjects entering this clinical study can get more 
attention from the investigator and deal with changes in their condition in a timely 
manner, which is conducive to the treatment of the subject's disease. 
2.2.3 Evaluation of potential risks and benefits 
The main study drugs in this study are adebelimab combined with carboplatin and nab-
binding shirtol. Among them, carboplatin and nab-binding shirt alcohol are the first-
line recommendations for the systemic treatment of head and neck cancer in the NCCN 
guidelines, and the adverse reactions and safety have also been proven by many studies. 
As a PD-L1 inhibitor, adebelimab has been confirmed in existing clinical studies to 
have a certain immune response effect on advanced tumors of the head and neck. At the 
same time, adebelimab has been studied in a large-sample phase III clinical study in 
small cell lung cancer in China, and its safety has been verified, and it was approved 
for marketing by the National Medical Products Administration on March 3, 2023. 
Therefore, the clinical study protocol has a low risk of tumor progression and serious 
adverse events in the treatment of head and neck squamous cell carcinoma, and the 
subjects have certain economic benefits under the drug donation policy of the 
pharmaceutical company. At the same time, in future studies, researchers will pay more 
attention to the subject's general condition and tumor treatment, and the subjects will 
also gain certain clinical benefits in the study. 
 
3. Purpose and endpoint of the study 
3.1 Purpose  
3.1.1 Main purpose 
The main objective of this study is to explore the efficacy of adebelimab combined with 
chemotherapy in patients with locally advanced resectable oral squamous cell 
carcinoma.  
3.1.2 Secondary Objectives  

 6 / 37 
 
The secondary objective of this study is to explore the prognostic impact of adebelimab 
combined with chemotherapy on patients with locally advanced resectable oral 
squamous cell carcinoma with different drug cycles. 
3.1.3 Exploratory purpose 
The exploratory objective of this study is to explore the effectiveness of adebelimab 
combined with chemotherapy in the treatment of locally advanced resectable oral 
squamous cell carcinoma with different drug cycles. To explore the correlation between 
biomarkers and the efficacy of combination regimens.  
3.2. Research indicators  
3.2.1 Main indicators and definitions  
Postoperative pathological complete response (PCR) rate: No residual tumor cells in 
the pathological sections of surgically resected primary lesions and lymph node 
specimens. The main judgment method is that the postoperative specimen is sent to the 
pathology department for fixation, sectioning, and observation. Two pathologists will 
read the radiograph to determine whether the tumor remains or not, and if there is a 
disagreement between the two, it will be discussed and decided by a third senior 
pathologist. 
3.2.2 Secondary indicators and definitions 
Major pathological response (MPR) rate: Proportion of patients with ≤ 10% of viable 
tumor cells in the primary lesion specimen. 
Tumor objective response (ORR) rate: The proportion of patients assessed by RECIST 
1.1 criteria as complete response (CR) and partial response (PR) after 
immunochemotherapy. 
2-year disease-free survival (EFS) rate: the proportion of patients who do not 
experience relapse or disease progression within 2 years after completion of all 
treatments.  
Overall survival (OS) at 2 and 5 years: Proportion of patients who survived at 2 and 5 
years after completion of all treatments. 
3.2.3 Security indicators 

 7 / 37 
 
The above safety indicators are based on the test results before the enrollment of the 
subjects, and the blood draw results of each cycle of treatment shall prevail, and will be 
interpreted by the investigator's team. 
 
4. Study population 
4.1 Selection criteria 
(1) Aged between 18 and 75 years; 
(2) Patients with stage III-IVB tumors with non-oropharyngeal cancer who have 
pathologically confirmed head and neck squamous cell carcinoma (oral cavity, 
including buccal, tongue, gingival, floor of mouth, palate, and maxillary sinuses) 
according to the 8th edition guidelines of the American Joint Committee on 
Cancer (AJCC);  
(3) Evaluating resectable tumors by head and neck surgeons before enrollment to rule 
out clinical evidence of distant metastasis; 
(4) At least one measurable tumor lesion according to RECIST 1.1, the efficacy 
evaluation criteria for solid tumors; 
(5) The performance status of the Eastern Cooperative Oncology Group (ECOG) was 
0-1; 
(6) Blood routine: white blood cell count (WBC) ≥3.0×109/L; Absolute neutrophil 
count (ANC) ≥ 1.5×109/L; Platelets (PLT) ≥ 100×109/L; Hemoglobin level 
(HGB) ≥ 9.0 g/dL (no corresponding supportive care such as transfusion and 
leukocyte increase within 7 days); 
(7) Liver function: aspartate aminotransferase (AST) and alanine aminotransferase 
(ALT) ≤ 2.5 times the upper limit of reference value (ULN) in patients without 
liver metastasis; albumin (ALB) ≥ 30 g/L; 
(8) Renal function: serum creatinine ≤1.5 times ULN or creatinine clearance (CrCl) ≥ 
50mL/min (using Cocroft/Galt formula); Urine protein (UPRO) < (++), or 24-
hour urine protein < 1.0 g; 
(9) HPV status of oropharyngeal cancer was determined using p16 IHC. If > 70% of 

 8 / 37 
 
tumor cells exhibit strong diffuse nuclei and cytoplasmic staining, the sample is 
considered p16 positive; 
(10) Have not participated in other clinical trial projects within the past 30 days; 
(11) Patients who voluntarily participate in this project and sign the informed consent 
form. 
4.2 Exclusion Criteria 
(1) The patient has abnormal blood indicators and abnormal liver and kidney function, 
and cannot tolerate the course of this clinical study after multidisciplinary 
consultation and evaluation; 
(2) The patient has previously suffered from tumors in other parts of the country, or has 
undergone anti-tumor treatment such as surgery, chemotherapy, and radiotherapy in the 
past; 
(3) Unable to complete the entire clinical research process due to personal, social and 
economic reasons; 
(4) Previous serious systemic diseases that cannot be cured or controlled by drugs. 
4.3 Lifestyle considerations 
If the subject needs to use drugs, treatments or surgeries unrelated to this study in the 
clinical study, the investigator needs to evaluate whether the reason for the need for the 
drug, treatment and surgical treatment is the adverse events caused by the study, such 
as accidents or other reasons that cause the subject to need additional treatment 
modalities, then consider whether the treatment has an impact on the course of the study, 
If the impact is too great, it is recommended that the subject receive conventional 
treatment after withdrawal and the subject data be sealed. 
4.4 Screening failed 
Screening failure refers to the situation where the subjects do not meet the inclusion 
criteria or fall under the exclusion criteria after multidisciplinary evaluation after 
enrollment and recruitment. This study will inform the subjects who failed the screening 
based on the results of multidisciplinary consultation and give the best treatment 
recommendations at present. 

 9 / 37 
 
4.5 Recruitment and Retention Strategies 
The main offline location is the Department of Oral and Maxillofacial Surgery of Sun 
Yat-sen Memorial Hospital, including but not limited to posters, leaflets, seminars, etc. 
to attract more subjects, and each interested patient will register on-site, leave contact 
information and continue to carry out one-on-one explanation of the plan. If the subject 
is financially difficult, the investigator team will assist the subject in applying for a 
public welfare fund to reduce the financial burden of the subject. 
 
5. Research design 
5.1 General design 
This study aims to explore the efficacy of PD-L1 inhibitors combined with carboplatin 
and nab-binding shirt alcohol in different cycles of treatment in resectable locally 
advanced oral squamous cell carcinoma, and to compare the differences between short-
course therapy (two cycles) and long-course therapy (three cycles). This study is a 
single-center, randomized phase II exploratory study. Block randomization was used to 
generate random sequences through a central random system. The specific operation is 
to allocate the subjects who meet the inclusion criteria to the short-course treatment 
group or the long-course treatment group in a ratio of 1:1, and the randomization form 
is generated by an independent statistician by a third-party randomizer independent of 
the research team through the Interactive Web Response System (IWRS), and the 
subjects who meet the randomization criteria are randomized through the 
randomization system, and the subjects are given a unique randomization number, 
which is recorded in the case report form (CRF). The block length is dynamic block 
size to ensure that the researcher cannot predict the grouping outcome. At the same time, 
this study uses blinded endpoint evaluation, and during the evaluation of outcome 
indicators (such as imaging results, pathological results, etc.), the evaluators (such as 
radiologists, pathologists) do not know the grouping of the subjects. During the study, 
patients should be followed up regularly, and the tumor regression rate, tumor residual 
rate and psychological changes of patients in the short-course group and the long-course 

 10 / 37 
 
group should be comparatively analyzed and recorded, so as to provide preliminary 
research data for subsequent neoadjuvant therapy studies with different drug cycles. 
5.2 Research and design process 
5.2.1 Study the specific implementation process 
This study starts with the recruitment of subjects, undergoes pathological biopsy to 
confirm the diagnosis, and is enrolled after initial screening according to the inclusion 
and exclusion criteria, and after signing the informed consent formThis study employs 
block randomization to generate random sequences through a central random system. 
The specific operation is to allocate the subjects who meet the inclusion criteria to the 
short-course treatment group or the long-course treatment group in a 1:1 ratio, and the 
randomization form is generated by an independent statistician and a third-party 
randomizer independent of the research team through the interactive web response 
system (IWRS), and the subjects who meet the randomization criteria are randomized 
through the randomization system, and the subjects are given a unique randomization 
number, which is recorded in the case report form (CRF). The block length is dynamic 
block size to ensure that the researcher cannot predict the grouping outcome. At the 
same time, this study uses blinded endpoint evaluation, and during the evaluation of 
outcome indicators (such as imaging results, pathological results, etc.), the evaluators 
(such as radiologists, pathologists) do not know the grouping of the subjects.  
Short-course group (two cycles): Albumin-bound paclitaxel 260 mg/m2, carboplatin 
AUC=5, and adebelimab 1200 mg intravenously on the first day of each three-week 
course of treatment every three weeks. A total of two cycles were performed, and 
surgery was performed 21 days after the end of the second cycle, and radiotherapy and 
chemotherapy were performed according to the pathological stage after surgery. 
Patients who did not require radiotherapy were maintained with a PD-L1 inhibitor 
(adebelimab) as a single agent, and patients who required chemoradiotherapy were 
maintained as a single agent at the same time, and the duration of medication for all 
patients was one year (from the time of the first dose at the initial diagnosis to the time 
of the last dose after surgery). 

 11 / 37 
 
Long-course group (3 cycles): Intravenous albumin-bound paclitaxel 260 mg/m2, 
carboplatin AUC=5, and adebelimab 1200 mg on the first day of each 3-week course 
every three weeks. A total of three cycles were performed, and surgery was performed 
21 days after the end of the third cycle, and radiotherapy and chemotherapy were 
performed according to the pathological stage after surgery. Patients who did not 
require radiotherapy were maintained with a PD-L1 inhibitor (adebelimab) as a single 
agent, and patients who required chemoradiotherapy were maintained as a single agent 
at the same time, and the duration of medication for all patients was one year (from the 
time of the first dose at the initial diagnosis to the time of the last dose after surgery). 
All enrolled patients were given conventional medication to prevent vomiting in each 
cycle, while dexamethasone was given intravenous injection before each dose for 
allergy prevention. 
5.2 Research schedule 
project 
sift 
Medication 
surgery 
Follow 
V1 
V2 
V3 
V4 
V5 
V6 
V7 
V8 
V9 
V10 
Follow-up time 
Before 
enrollment 
1 day 
After 
enrollment 
1 day 
After 
V2 
3 
weeks 
After 
V3 
3 
weeks 
3 weeks 
after V4 
or 
3 weeks 
after V3 
Postoperatively 
1 month 
Postoperatively 
3 months 
Postoperatively 
6 months 
Postoperatively 
1 year 
Postoperatively 
2 years 
sign 
Informed consent 
√ 
 
 
 
 
 
 
 
 
 
Enter the queue 
screening 
√ 
 
 
 
 
 
 
 
 
 
population 
Statistical data 
√ 
 
 
 
 
 
 
 
 
 
medical history 
√ 
 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
ECOG score 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
physical 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 

 12 / 37 
 
examination 
Vital signs 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
electrocardiogram 
√ 
 
√ 
√ 
√ 
 
 
 
 
 
Blood routine 
√ 
 
√ 
√ 
√ 
√ 
√ 
 
 
 
Blood biochemistry 
√ 
 
√ 
√ 
√ 
√ 
√ 
 
 
 
Liver function 
√ 
 
√ 
√ 
√ 
√ 
√ 
 
 
 
Coagulation 
function 
√ 
 
√ 
√ 
√ 
√ 
√ 
 
 
 
Pathological 
examination 
PD-L1 assay 
√ 
 
 
 
√ 
 
 
 
 
 
HPV test 
√ 
 
 
 
 
 
 
 
 
 
Echocardiography 
√ 
 
 
 
 
 
 
 
 
 
Infectious disease 
examination 
Hepatitis B, 
hepatitis C, HIV, 
syphilis 
√ 
 
 
 
 
 
 
 
 
 
Imaging tests 
√ 
 
 
 
√ 
 
 
√ 
√ 
√ 
complication 
and adverse event 
assessment 
 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
5.3 Ways to reduce bias 
Block randomization was used to generate random sequences through a central random 
system. The specific operation is to allocate the subjects who meet the inclusion criteria 
to the short-course treatment group or the long-course treatment group in a 1:1 ratio, 
and the randomization form is generated by an independent statistician and a third-party 
randomizer independent of the research team through the interactive web response 
system (IWRS), and the subjects who meet the randomization criteria are randomized 

 13 / 37 
 
through the randomization system, and the subjects are given a unique randomization 
number, which is recorded in the case report form (CRF). The block length is dynamic 
block size to ensure that the researcher cannot predict the grouping outcome. At the 
same time, this study uses blinded endpoint evaluation, and during the evaluation of 
outcome indicators (such as imaging results, pathological results, etc.), the evaluators 
(such as radiologists, pathologists) do not know the grouping of the subjects. 
Standardized operations to ensure that researchers perform the study according to 
unified standards, and that the treatment and medication processes of all patients are 
consistent. Ensure sufficient sample size to reduce random error. Regularly review data 
collection and processing processes to ensure study integrity and subject safety, 
ensuring data accuracy. Blinded endpoint assessment, during the evaluation of outcome 
indicators (such as imaging results, pathological results, etc.), the evaluator (such as 
radiologists, pathologists) is unaware of the grouping of subjects.  
5.4 Definition of end of study 
End of this study is defined as the last subject to complete the last follow-up or lost to 
follow-up or die. 
5.5 Statistical analysis 
5.5.1 Sample size and calculation basis 
The primary endpoint of this study is the pathological complete response rate of 
the short-course group and the long-course group, and the signed informed subjects are 
randomly arranged to enter the short-course group or the long-course group. This study 
is defined as a pre-experimental study, considering the disgrouping rate of about 15%, 
a total of 70 people are planned to be included in the short-course group (two cycles) 
and the long-course group (three cycles), and the randomization is 1:1, that is, 35 people 
will be included in the short-course group and the long-course group. 
5.5.2 Data analysis set 
Statistical analysis will be calculated using SAS statistical software (V.9.4, SAS 
Institute) statistical analysis software, and the main indicators will be two-sided test, 
and the control type 1 error α is 0.05. If confidence intervals need to be calculated, if 

 14 / 37 
 
otherwise specified, calculate 95% confidence intervals on both sides. 
(1) Full analysis set (FAS): composed of all subjects who received at least one 
drug/treatment and received efficacy evaluation. This dataset was derived from all 
subjects after minimal and reasonable method of rejecting subjects. 
(2) safety analysis set (SS): a group of people who have used at least one drug/received 
one treatment and have at least one safety evaluation data. In the safety analysis, all 
patients will be analyzed by the actual drug group received. 
(3) Per-protocal set (PPS): All subjects who met the trial protocol and did not use 
concomitant drugs that affected the efficacy evaluation, had good medication 
compliance (between 80% and 120%), excluded major protocol violations, and were 
judged to have a significant impact on the results. All protocol deviations from the trial 
protocol that result in the exclusion of subjects from the conforming protocol set will 
be described in detail in the Statistical Analysis Plan (SAP) and completed prior to data 
lock-in. 
5.5.3 Statistical analysis plan 
Demographic and other baseline characteristics: Based on the FAS set, the demographic 
data, medical history, vital signs, and other baseline data are statistically described, in 
which the mean, standard deviation, minimum, maximum, and median are given for the 
measurement data (age, BMI, weight, blood pressure, etc.); Aggregate data (gender, 
tobacco and alcohol history, etc.) give the frequency and corresponding percentages. 
Efficacy index analysis: The main index was a two-sided test, and the control α of 
error was 0.05. The primary endpoint (PCR rate) was estimated at points, and the 
Clopper-Pearson exact probability method was used to estimate the two-sided 95% 
confidence interval. The secondary efficacy indicators were analyzed using FAS and 
PPS analysis sets. For survival measures, median survival time and its two-sided 95% 
confidence intervals were calculated. For the rates of each indicator, point estimation 
was performed and Clopper-Pearson exact probability method was used to estimate the 
two-sided 95% confidence interval. For the continuity index, if it meets the normal 
distribution, its mean and two-sided 95% confidence interval are calculated based on 

 15 / 37 
 
the normal distribution method, otherwise the median and two-sided 95% confidence 
interval are calculated based on the percentile method. 
Safety index analysis: The SS set was used to statistically describe the safety indicators 
such as the incidence of adverse events/serious adverse events and the incidence of 
adverse reactions, and the details of each adverse event for each subject were described 
in a list, including the type and severity of adverse events. Compare and evaluate the 
changes before and after treatment of laboratory indicators, vital signs, 
electrocardiogram and other safety-related indicators, and give a statistical description 
of the clinical evaluation (normal, abnormal no clinical significance, abnormal 
clinically significant, unchecked) before and after treatment. 
Principles for the processing of missing/deleted/lost data are filled in by LOCF (last 
observation carried forward) for the analysis of the main indicators, that is, the data of 
the main indicators that cannot be observed are filled with the last observation data; 
Secondary and security metrics are not filled. 
 
6. Research intervention 
6.1 Study intervention content 
This study starts with the recruitment of subjects, undergoes pathological biopsy to 
confirm the diagnosis, and is enrolled after initial screening according to the inclusion 
and exclusion criteria, and after signing the informed consent form。 In this study, 
block randomization was adopted, and subjects who met the inclusion criteria were 
assigned to the short-course treatment group or the long-course treatment group in a 1:1 
ratio by computer-generated random sequences, and the random sequences were 
generated by independent statisticians using statistical software (such as SAS or R), and 
the block length was set to dynamic blocks to ensure balance between groups. Random 
sequence concealment is sealed and opaque envelopes to ensure that researchers cannot 
predict the grouping results. After the subjects sign the informed consent form and 
complete the screening assessments, the randomization envelope will be opened by the 
study center personnel. Automatically assign subjects to the short-course or long-course 

 16 / 37 
 
treatment group based on the results in the envelope, and the assignment results cannot 
be changed. The randomization number is tied to the subject's unique ID and recorded 
in the case report form (CRF). At the same time, this study uses blinded endpoint 
evaluation, and during the evaluation of outcome indicators (such as imaging results, 
pathological results, etc.), the evaluators (such as radiologists, pathologists) do not 
know the grouping of the subjects. The following are specific intervention methods: 
Short-course group (two cycles): Albumin-bound paclitaxel 260 mg/m2, carboplatin 
AUC=5, and adebelimab 1200 mg intravenously on the first day of each three-week 
course of treatment every three weeks. A total of two cycles were performed, and 
surgery was performed 21 days after the end of the second cycle, and radiotherapy and 
chemotherapy were performed according to the pathological stage after surgery. 
Patients who did not require radiotherapy were maintained with a PD-L1 inhibitor 
(adebelimab) as a single agent, and patients who required chemoradiotherapy were 
maintained as a single agent at the same time, and the duration of medication for all 
patients was one year (from the time of the first dose at the initial diagnosis to the time 
of the last dose after surgery). 
Long-course group (3 cycles): Intravenous albumin-bound paclitaxel 260 mg/m2, 
carboplatin AUC=5, and adebelimab 1200 mg on the first day of each 3-week course 
every three weeks. A total of three cycles were performed, and surgery was performed 
21 days after the end of the third cycle, and radiotherapy and chemotherapy were 
performed according to the pathological stage after surgery. Patients who did not 
require radiotherapy were maintained with a PD-L1 inhibitor (adebelimab) as a single 
agent, and patients who required chemoradiotherapy were maintained as a single agent 
at the same time, and the duration of medication for all patients was one year (from the 
time of the first dose at the initial diagnosis to the time of the last dose after surgery). 
All enrolled patients were given conventional medication to prevent vomiting in each 
cycle, while dexamethasone was given intravenous injection before each dose for 
allergy prevention. 
6.2 Preparation/Handling/Storage/Duties 

 17 / 37 
 
Medication use must be documented in the patient's medical record and in the 
appropriate location of the CRF. After enrollment and at the 1st and 2nd month follow-
up, the executive nurse will receive the corresponding numbered drugs from the drug 
administrator, and the remaining drugs and packaging boxes will be returned to the drug 
administrator. If the drug is found to be damaged at the time of collection or during the 
preparation process, this box of drugs cannot be used, the damaged drugs will be treated 
as empty bottles, and other undamaged drugs will be returned to the drug administrator 
together with the packaging box. The research center should have a dedicated person 
responsible for the management of the trial drug, including receiving, distributing, 
counting and recycling. The investigator should ensure that the test drug is stored in a 
safe, independent and locked place in the study center, and the storage conditions 
should meet the preservation requirements of the trial drug. No one can be contacted 
without the consent of the investigator. Empty boxes should be stored and managed in 
the same way as the test drug. 
6.3 Study intervention adherence 
After each dose, the subject should be asked to return to the research center for review 
periodically, and the compliance of the study can be verified according to the subject's 
review situation. In the follow-up visit, the research team members must communicate 
with the subject by telephone and reasonably arrange the subject's follow-up visit. 
6.4 Concomitant treatment 
If the subject has hypertension, diabetes, coronary heart disease and other diseases that 
require long-term drug control, the investigator and relevant specialists should evaluate 
the impact of the disease and the relevant research protocol and determine the dosage 
and duration of adjuvant drugs. 
6.4.1 Rescue 
The life-threatening dangers of subjects during the implementation of the clinical 
research plan should be implemented in accordance with the clinical rescue plan, such 
as cardiopulmonary resuscitation, emergency airway management, emergency surgical 
treatment, relevant records during hospitalization should be recorded in the medical 

 18 / 37 
 
record system, and the occurrence after discharge should be recorded in the adverse 
event record form. 
 
7. Study intervention discontinuation/subject suspension and withdrawal 
7.1 Discontinuation of study intervention 
If the level 3 adverse events of CTCAE version 5.0 standard reach 30% of the number 
of subjects in this study, the study should be suspended, and the drug safety of the study 
protocol should be discussed, and the dose of the drug in the study protocol should be 
adjusted (the chemotherapy dose was adjusted to 50% of the recommended dose, and 
adebelimab was suspended), and follow-up should continue during the suspension of 
the study to maintain the follow-up records of the original subjects. 
7.2 Subject discontinuation/withdrawal from the study 
When the subject is dissatisfied with the treatment effect of the study protocol or his 
own finances, he or she should actively communicate with the subject, encourage the 
subject to actively treat and help him apply for public welfare funds to complete the 
treatment. 
7.3 Loss to follow-up 
The investigator should retain the contact information of multiple subjects and the 
contact information of the subject's family after the subject is enrolled, and the 
investigator should actively contact the subject by phone after the subject is discharged 
from the hospital, keep abreast of the condition and arrange the subject to be admitted 
to the hospital in advance for the next stage of treatment. 
 
8. Adverse events and unexpected events 
Adverse events (AEs) are untoward medical events that occur after a subject 
receives treatment, but are not necessarily causally related to treatment. An adverse 
event can be any unfavorable and unintended sign (including abnormal laboratory 
findings), symptoms, or disease associated with the use of treatment measures in time, 
regardless of whether they are related to treatment measures. This includes, but is not 

 19 / 37 
 
limited to: (1) exacerbation of pre-existing disease prior to the use of study treatment 
measures; (2) Increased frequency or exacerbation of episodic events that already 
existed before the use of study treatment measures; (3) Abnormal changes detected or 
diagnosed after the use of study treatment measures, although such abnormal changes 
may have existed before treatment; (4) Exacerbation of disease or symptoms that 
already persisted before the start of the study. 
In the trial, the investigator should conduct a comprehensive analysis according to 
the specific circumstances of the adverse events and the subject's past history, 
concomitant diseases and concomitant medications, etc., to judge the relationship 
between adverse events and treatment measures. The relationship between adverse 
events and treatment measures is divided into "definitely related, likely related, possibly 
related, possibly irrelevant, and unrelated" :( 1) unrelated: adverse events are not related 
to treatment measures; (2) May be irrelevant: the occurrence of adverse events is more 
likely to be related to other factors, such as medication or concomitant diseases, or the 
time of occurrence of the event indicates that it is unlikely to have a causal relationship 
with treatment measures; (3) May be related: The occurrence of adverse events may be 
caused by treatment measures. It cannot be ruled out whether it may be caused by other 
factors, such as medication or concomitant diseases.    The occurrence of adverse 
events and treatment measures had a reasonable chronological sequence, and the causal 
relationship between events and treatment measures could not be ruled out. (4) It is 
likely to be related: the occurrence of adverse events may be caused by treatment 
measures. There is a reasonable chronological sequence of events and treatment 
measures; (5) Affirmation: The type of adverse event has been confirmed to be caused 
by treatment measures and cannot be explained by other reasons, such as medication 
and concomitant diseases. The timing of the event strongly suggests causation. 
The criteria for determining the severity of adverse events can be based on the 
common adverse event evaluation criteria CTCAE version 5.0 (U.S. Department of 
Health and Human Services). If you are outside the above list of criteria, you can refer 
to the following criteria: (1) Mild: symptomatic or signful but tolerable; (2) moderate; 

 20 / 37 
 
Discomfort is enough to interfere with normal life; (3) Severe: Unable to carry out 
normal activities. All information about adverse events, whether mentioned by the 
patient, discovered by the investigator, or discovered through physical examination, 
laboratory tests, etc., should be recorded in the study medical record and case report 
form. During the trial, the time, duration, signs and severity of adverse events, measures 
taken, outcomes, and relationship to treatment measures should be carefully observed 
and recorded, and appropriate follow-up should be performed. 
Possible adverse events include: (1) Chemotherapy complications: common 
complications caused by albumin shirt alcohol are: neutropenia; bradycardia of the 
cardiovascular system; skin reactions; Complications after carboplatin treatment 
include: bone marrow suppression; Anaphylaxis; peripheral neurotoxicity; nausea and 
vomiting; Treatment: If there are adverse reactions to chemotherapy above grade 3, the 
chemotherapy dose will be halved in subsequent treatment; If the follow-up 
chemotherapy drug injection cannot be tolerated after being evaluated by the 
investigator, the tumor will be removed after surgical evaluation after complication 
treatment; (2) Tumor hyperprogression: If the subject finds tumor hyperprogression 
during clinical examination during the 3 courses of treatment, the imaging examination 
will confirm whether there is tumor hyperprogression, and the tumor will be removed 
after preoperative evaluation and continued treatment in the oncology department. (3) 
Surgical complications: anesthesia accidents occurring in the perioperative period; 
cardiovascular and cerebrovascular accidents; Intraoperative important neurovascular 
injury; The flap survived after surgery; Postoperative reoperation is possible; Treatment: 
Clinical treatment will be carried out according to the complications of normal surgery, 
and at the same time, detailed records will be recorded in the subject's medical record 
to evaluate whether the surgical complication is related to the preoperative clinical trial; 
(4) Immune complications (adebelimab): immune pneumonia; immune hepatitis; 
Diarrhoea; Nephritis; hypothyroidism; skin reactions; adrenalinetis; thrombocytopenia; 
Treatment: If there is a grade 2 adverse reaction, the administration will be suspended 
until it recovers to grade 0-1, and if there is a grade 3 adverse reaction, the drug will be 

 21 / 37 
 
permanently stopped. 
The investigator should use medical terms/concepts to document AEs or SAEs. Its 
type, degree, time of appearance, duration, treatment measures, and treatment are 
recorded in detail. On the basis of comprehensive consideration of comorbidities and 
concomitant medications, its correlation with the study treatment measures was 
evaluated. All AEs (including SAEs) should be documented on the CRF's adverse event 
table. Any patient must be evaluated for toxicity as long as treatment is administered. 
The occurrence of any adverse events (AEs) should be graded according to the NCI 
Common AE Grading Criteria (NCI-CTCAE version 5.0). 
 
9. Data collection and management 
9.1 Case Report Forms/Electronic Data Records 
Before the start of the study, a Redcap electronic database or EDC database was 
established based on the contents of the paper case report form. 
9.2 Data management 
The original data should be uniformly recorded in the research medical record, and 
according to the content of the research medical record, the investigator himself or the 
designated or authorized trained personnel can complete the completion of the case 
report form and the data entry in the electronic database to ensure the completeness and 
accuracy of the information. In order to ensure the accuracy of the data, the researcher 
conducts self-inspection no less than twice a year, regularly assigns personnel to the 
sub-center for project quality control, and accepts inspections by hospital and school 
management departments. If it is found that the data registered in the case report 
form/electronic database is inconsistent with the original record (study medical record), 
the investigator should organize timely verification of the data, modify the errors in 
accordance with the requirements of GCP regulations, and explain accordingly if 
necessary. 
 
10. Ethical requirements 

 22 / 37 
 
This study complies with the Good Practice for Drug Clinical Trials and the 
Measures for the Administration of Investigator-initiated Clinical Research in 
Healthcare Institutions (Trial) and the Declaration of Helsinki. This study can only be 
carried out after the protocol is approved by the Ethics Committee of our hospital before 
the trial begins. During the research process, if the protocol must be revised, the revised 
protocol must be resubmitted to the ethics committee for review, and the researcher 
must wait until the ethics committee agrees before implementing the new plan. 
Each enrolled patient must sign an informed consent form. A copy of the informed 
consent form and contact information of the investigator and ethics committee must be 
provided to the subject. This study will collect clinical data and personal information 
of research subjects for scientific research, which will involve the privacy rights of 
patients. The participants and data analysts of this study have signed confidentiality 
agreements and will not disclose patients' personal information and disease-related 
information to any individuals and institutions unrelated to this study. The collected 
patient data is managed in a unified manner to prevent personal privacy leakage. 
 
11. References 
[1] Siegel RL, Miller KD, Fuchs HE, Jemal A. Cancer statistics, 2022. CA Cancer J 
Clin. 2022; 72(1):7-33.  
[2] Cooper JS, Pajak TF, Forastiere AA, et al. Postoperative concurrent radiotherapy 
and chemotherapy for high-risk squamous-cell carcinoma of the head and neck. N Engl 
J Med. 2004; 350(19):1937-1944. 
[3] Bernier J, Domenge C, Ozsahin M, et al. Postoperative irradiation with or without 
concomitant chemotherapy for locally advanced head and neck cancer. N Engl J Med. 
2004; 350(19):1945-1952.  
[4] Zhong LP, Zhang CP, Ren GX, et al. Randomized phase III trial of induction 
chemotherapy with docetaxel, cisplatin, and fluorouracil followed by surgery versus 
up-front surgery in locally advanced resectable oral squamous cell carcinoma. J Clin 
Oncol. 2013; 31(6):744-751.  
[5] Burtness B, Harrington KJ, Greil R, et al. Pembrolizumab alone or with 
chemotherapy versus cetuximab with chemotherapy for recurrent or metastatic 
squamous cell carcinoma of the head and neck (KEYNOTE-048): a randomised, open-
label, phase 3 study. Lancet. 2019; 394(10212):1915-1928.  
[6] Li B, Xie S, Han J, et al. Neoadjuvant chemoimmunotherapy in resectable locally 
advanced oral squamous cell carcinoma: a single-center retrospective cohort study. Int 

 23 / 37 
 
J Surg. 2025; 111(1):781-790. Published 2025 Jan 1.  
[7] Herbst RS, Soria JC, Kowanetz M, et al. Predictive correlates of response to the 
anti-PD-L1 antibody MPDL3280A in cancer patients. Nature. 2014; 515(7528):563-
567. 
[8] Wang Y, Zhou S, Yang F, et al. Treatment-Related Adverse Events of PD-1 and PD-
L1 Inhibitors in Clinical Trials: A Systematic Review and Meta-analysis. JAMA Oncol. 
2019; 5(7):1008-1019.  
[9] Ohaegbulam KC, Assal A, Lazar-Molnar E, Yao Y, Zang X. Human cancer 
immunotherapy with antibodies to the PD-1 and PD-L1 pathway. Trends Mol Med. 
2015; 21(1):24-33.  
[10] De Sousa Linhares A, Battin C, Jutz S, et al. Therapeutic PD-L1 antibodies are 
more effective than PD-1 antibodies in blocking PD-1/PD-L1 signaling. Sci Rep. 2019; 
9(1):11472.   
[11] Dirix LY, Takacs I, Jerusalem G, et al. Avelumab, an anti-PD-L1 antibody, in 
patients with locally advanced or metastatic breast cancer: a phase 1b JAVELIN Solid 
Tumor study. Breast Cancer Res Treat. 2018; 167(3):671-686.  
[12] Finn RS, Qin S, Ikeda M, et al. Atezolizumab plus Bevacizumab in Unresectable 
Hepatocellular Carcinoma. N Engl J Med. 2020; 382(20):1894-1905.  
[13] Rittmeyer A, Barlesi F, Waterkamp D, et al. Atezolizumab versus docetaxel in 
patients with previously treated non-small-cell lung cancer (OAK): a phase 3, open-
label, multicentre randomised controlled trial. Lancet. 2017; 389(10066):255-265.  
[14] Wang J, Zhou C, Yao W, et al. Adebrelimab or placebo plus carboplatin and 
etoposide as first-line treatment for extensive-stage small-cell lung cancer 
(CAPSTONE-1): a multicentre, randomised, double-blind, placebo-controlled, phase 3 
trial. Lancet Oncol. 2022; 23(6):739-747.  
[15] Colevas AD, Bahleda R, Braiteh F, et al. Safety and clinical activity of 
atezolizumab in head and neck cancer: results from a phase I trial. Ann Oncol. 2018; 
29(11):2247-2253.  
[16] Dindo D, Demartines N, Clavien PA. Classification of surgical complications: a 
new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann 
Surg. 2004; 240(2):205-213.  
[17] Rashid R, Sohrabi C, Kerwan A et al. The STROCSS 2024 guideline: 
strengthening the reporting of cohort, cross-sectional and case-control studies in surgery. 
Int J Surg. 2024; 110(6):3151-65. 
[18] Bray F, Laversanne M, Sung H, et al. Global cancer statistics 2022: GLOBOCAN 
estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA 
Cancer J Clin. 2024; 74(3):229-263. 
[19] Kim MJ, Ahn KM. Prognostic factors of oral squamous cell carcinoma: the 
importance of recurrence and pTNM stage. Maxillofac Plast Reconstr Surg. 2024; 
46(1):8. Published 2024 Mar 4.  
[20] Geum DH, Roh YC, Yoon SY, et al. The impact factors on 5-year survival rate in 
patients operated with oral cancer. J Korean Assoc Oral Maxillofac Surg. 2013; 
39(5):207-216.  
[21] Kim BG, Kim JH, Kim MI, et al. Retrospective study on factors affecting the 

 24 / 37 
 
prognosis in oral cancer patients who underwent surgical treatment only. Maxillofac 
Plast Reconstr Surg. 2016; 38(1):3. Published 2016 Jan 16.  
[22] Zanoni DK, Montero PH, Migliacci JC, et al. Survival outcomes after treatment of 
cancer of the oral cavity (1985-2015). Oral Oncol. 2019; 90:115-121.  
[23] Li J, Luo Z, Jiang S, Li J. Advancements in neoadjuvant immune checkpoint 
inhibitor therapy for locally advanced head and neck squamous Carcinoma: A narrative 
review. Int Immunopharmacol. 2024; 134:112200.  
[24] Seiwert TY, Burtness B, Mehra R, et al. Safety and clinical activity of 
pembrolizumab for treatment of recurrent or metastatic squamous cell carcinoma of the 
head and neck (KEYNOTE-012): an open-label, multicentre, phase 1b trial. Lancet 
Oncol. 2016; 17(7):956-965.  
[25] Ferris RL, Blumenschein G Jr, Fayette J, et al. Nivolumab for Recurrent 
Squamous-Cell Carcinoma of the Head and Neck. N Engl J Med. 2016; 375(19):1856-
1867.  
[26] Harrington KJ, Burtness B, Greil R, et al. Pembrolizumab With or Without 
Chemotherapy in Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma: 
Updated Results of the Phase III KEYNOTE-048 Study. J Clin Oncol. 2023; 41(4):790-
802.  
[27] Mo DC, Huang JF, Luo PH, Chen L, Zou B, Wang HL. PD-1/PD-L1 inhibitor plus 
chemotherapy versus standard of care in the first-line treatment for recurrent or 
metastatic head and neck squamous cell carcinoma. Eur Arch Otorhinolaryngol. 2023; 
280(1):1-9. 
[28] Chen S, Yang Y, Wang R, Fang J. Neoadjuvant PD-1/PD-L1 inhibitors combined 
with chemotherapy had a higher ORR than mono-immunotherapy in untreated HNSCC: 
Meta-analysis. Oral Oncol. 2023; 145:106479.  
[29] Tang Q, Chen Y, Li X, et al. The role of PD-1/PD-L1 and application of immune-
checkpoint inhibitors in human cancers. Front Immunol. 2022; 13:964442. Published 
2022 Sep 13.  
[30] Wang SJ, Dougan SK, Dougan M. Immune mechanisms of toxicity from 
checkpoint inhibitors. Trends Cancer. 2023; 9(7):543-553.  
[31] Yin Q, Wu L, Han L, et al. Immune-related adverse events of immune checkpoint 
inhibitors: a review. Front Immunol. 2023; 14:1167975. Published 2023 May 25.  
[32] Sonpavde GP, Grivas P, Lin Y, Hennessy D, Hunt JD. Immune-related adverse 
events with PD-1 versus PD-L1 inhibitors: a meta-analysis of 8730 patients from 
clinical trials. Future Oncol. 2021; 17(19):2545-2558.  
[33] Chen DS, Irving BA, Hodi FS. Molecular pathways: next-generation 
immunotherapy--inhibiting programmed death-ligand 1 and programmed death-1. Clin 
Cancer Res. 2012; 18(24):6580-6587. 
[34] Zandberg DP, Algazi AP, Jimeno A, et al. Durvalumab for recurrent or metastatic 
head and neck squamous cell carcinoma: Results from a single-arm, phase II study in 
patients with ≥25% tumour cell PD-L1 expression who have progressed on platinum-
based chemotherapy. Eur J Cancer. 2019; 107:142-152. 
[35] Lancaster GA, Dodd S, Williamson PR. Design and analysis of pilot studies: 
recommendations for good practice. J Eval Clin Pract. 2004; 10(2):307-312.  

 25 / 37 
 
Informed consent 
 
Project Name: A single-center, randomized, phase II exploratory study of adebelimab combined 
with carboplatin and nab-binding squamous alcohol in the treatment of resectable locally 
advanced oral squamous cell carcinoma 
Research unit: Sun Yat-sen Memorial Hospital, Sun Yat-sen University 
Version number: V3.0 
Version date: 2025-07-21 
 
Dear Study Participants, 
We invite you to participate in a study titled "A Single-center, Randomized, Phase II Exploratory 
Study of Adebelimab in Combination With Carboplatin, Nab-Binding Purple Platinol in the Treatment 
of Resectable Locally Advanced Oral Squamous Cell Carcinoma".  
This informed consent form will detail the relevant information, purpose, research process, any 
potential benefits and risks, and your rights before you make a decision to participate in this study, 
please read the following information carefully, and if you have any questions, please ask the study 
doctor or researcher if you have any questions. You can discuss it with your family as well as friends 
and have plenty of time to think about it. If you are enrolled in another study, let your study doctor or 
researcher know. 
If you have learned more about this study and decide to participate, you will need to sign this 
informed consent form and we will provide you with a copy of the signed informed consent form. 
1、Background 
According to the latest data from the International Agency for Research on Cancer, the global 
incidence of head and neck cancer in 2022 ranks among the top ten new cancer incidences in the world. 
Among them, the treatment guidelines for locally advanced head and neck squamous cell carcinoma 
(HNSCC) are risk-adapted adjuvant radiotherapy with or without platinum-based chemotherapy, or 
definitive concurrent chemoradiotherapy after surgical resection. However, despite aggressive 
combination therapy, patients with locally advanced HNSCC remain at high risk of recurrence, distant 
metastasis, and death. With the proposal of the treatment concept of preoperative induction 

 26 / 37 
 
chemotherapy, clinical studies have shown that patients who achieve tumor remission after preoperative 
induction chemotherapy have a higher survival rate and lower risk of distant metastasis, but the 
complete response rate of tumor pathology after surgery is low, and satisfactory results have not been 
achieved. 
Tumor immunotherapy provides the possibility to solve the above dilemma. At present, immune 
checkpoint inhibitors (ICIs) are widely used in oral squamous cell carcinoma (OSCC). A clinical study 
(KEYNOTE-048) showed that pembrolizumab (PD-1) combined with chemotherapy significantly 
improved the survival of patients with recurrent or metastatic oral squamous cell carcinoma, and has 
now become the first-line treatment option according to NCCN guidelines. Meanwhile, in a 
retrospective study, Neoadjuvant chemoimmunotherapy (NACL) showed safe and encouraging 
efficacy in patients with locally advanced resectable OSCC. Among the 104 patients who received 
NACI, the pathological complete response (PCR) rate was 47.1%, the major pathological response 
(MPR) rate was 65.4%, and the expected 3-year disease-free survival (DFS) rate and overall survival 
(Overall survival, OS) rates of 89.0% and 91.3%, suggesting that NACI can effectively improve the 
postoperative pathological remission rate and improve the prognosis of patients. 
PD-L1 and PD-L2 are two ligands of PD-1. PD-L1 can be expressed by both tumor and immune 
cells, and PD-L1 is a useful biomarker for predicting the response to PD-1/PD-L1 antibodies in patients 
with different types of cancer. PD-L1 plays a role in inhibiting the cancer-immune cycle by binding to 
negative regulators such as PD-1 and B7.1 activated by T cells. PD-L1 inhibitors are currently less used 
in tumor treatment in clinical practice, mainly in small cell lung cancer. In terms of head and neck 
squamous cell carcinoma, there are also phase I clinical studies that have confirmed the therapeutic 
safety and tumor activity of PD-L1 inhibitors. In one meta-analysis, PD-1 inhibitors had a higher overall 
average incidence of grade 3 or higher adverse events than PD-L1 inhibitors (OR, 1.58; 95% CI, 1.00-
2.54), possibly because PD-L1 inhibitors bind PD-L1 on the surface of tumor cells and antigen-
presenting cells, but retain the normal function of PD-L2, thereby reducing the risk of potential 
autoimmune reactions and adverse events. Therefore, PD-L1 inhibitors may have more therapeutic 
potential than PD-1 inhibitors. 
Previous studies have shown that PD-L1 inhibitor (adebelimab) combined with chemotherapy has 
shown satisfactory efficacy, confirming that PD-L1 inhibitor (adebelimab) can effectively increase the 

 27 / 37 
 
PCR rate. However, due to the accumulation of toxic effects of drugs, patients' tolerance to adverse 
reactions decreases, increasing the risk of serious adverse events and increasing the psychological stress 
of patients. On this basis, this study aims to explore the efficacy of adebelimab (PD-L1 inhibitor) 
combined with chemotherapy in locally advanced oral squamous cell carcinoma with different drug 
cycles, and further verify the efficacy and safety of PD-L1 inhibitor combined with chemotherapy in 
the treatment of locally advanced oral squamous cell carcinoma. 
 
2. Research purpose 
1. Main objective: The main purpose of this study is to explore the efficacy of adebelimab combined 
with chemotherapy in patients with locally advanced resectable oral squamous cell carcinoma. 
2. Secondary objective: The secondary objective of this study is to explore the prognostic impact of 
adebelimab combined with chemotherapy on patients with locally advanced resectable oral squamous 
cell carcinoma. 
3. Exploratory objective: The exploratory objective of this study is to explore the effectiveness of 
adebelimab combined with chemotherapy in the treatment of locally advanced resectable oral squamous 
cell carcinoma with different drug cycles. To explore the correlation between biomarkers and the 
efficacy of combination regimens. 
 
3. Introduction to clinical research projects 
1. Research object 
A total of 70 participants will be included in this study. The selection exclusion criteria are as follows: 
(1) Aged between 18 and 75 years; 
(2) Patients with stage III-IVB tumors with non-oropharyngeal cancer who have pathologically 
confirmed head and neck squamous cell carcinoma (oral cavity, including buccal, tongue, gingival, 
floor of mouth, palate, and maxillary sinuses) according to the 8th edition guidelines of the American 
Joint Committee on Cancer (AJCC); 
(3) Evaluating resectable tumors by head and neck surgeons before enrollment to rule out clinical 
evidence of distant metastasis; 
(4) At least one measurable tumor lesion according to RECIST 1.1, the efficacy evaluation criteria for 

 28 / 37 
 
solid tumors; 
(5) The performance status of the Eastern Cooperative Oncology Group (ECOG) was 0-1; 
(6) Blood routine: white blood cell count (WBC) ≥3.0×109/L; Absolute neutrophil count (ANC) ≥ 
1.5×109/L; Platelets (PLT) ≥ 100×109/L; Hemoglobin level (HGB) ≥ 9.0 g/dL (no corresponding 
supportive care such as transfusion and leukocyte increase within 7 days); 
(7) Liver function: aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 times 
the upper limit of reference value (ULN) in patients without liver metastasis; albumin (ALB) ≥ 30 g/L; 
(8) Renal function: serum creatinine ≤1.5 times ULN or creatinine clearance (CrCl) ≥ 50mL/min (using 
Cocroft/Galt formula); Urine protein (UPRO) < (++), or 24-hour urine protein < 1.0 g; 
(9) HPV status of oropharyngeal cancer was determined using p16 IHC. If > 70% of tumor cells exhibit 
strong diffuse nuclei and cytoplasmic staining, the sample is considered p16 positive; 
(10) Have not participated in other clinical trial projects within the past 30 days; 
(11) Patients who voluntarily participate in this project and sign the informed consent form. 
Exclusion Criteria: 
(1) The patient has abnormal blood indicators and abnormal liver and kidney function, and cannot 
tolerate the course of this clinical study after multidisciplinary consultation and evaluation; 
(2) The patient has previously suffered from tumors in other parts of the country, or has undergone anti-
tumor treatment such as surgery, chemotherapy, and radiotherapy in the past; 
(3) Unable to complete the entire clinical study due to personal, social and economic reasons; 
(4) Previous serious systemic diseases that cannot be cured or controlled by drugs. 
2. Study design 
This study aims to explore the efficacy of PD-L1 inhibitors combined with carboplatin and nab-binding 
shirt alcohol in different cycles of treatment in resectable locally advanced oral squamous cell 
carcinoma, and to compare the differences between short-course therapy (two cycles) and long-course 
therapy (three cycles). This study is a single-center, randomized phase II clinical study. The study was 
a randomized, open-label trial in which patients were randomized to receive either short-course therapy 
(two cycles) or long-course therapy (three cycles) in a randomized ratio of 1:1. After enrollment, the 
subjects were randomly assigned to the short-course group or the long-course group, and received 
periodic treatment according to the standard protocol of the trial. During the study, patients should be 

 29 / 37 
 
followed up regularly, and the tumor regression rate, tumor residual rate and psychological changes of 
patients in the short-course group and the long-course group should be comparatively analyzed and 
recorded, so as to provide preliminary research data for subsequent neoadjuvant therapy studies with 
different drug cycles. 
3. Research time limit: August 2025 to December 2027 
 
4. Clinical research process 
(1) Signed informed consent. 
(2) Conduct enrollment screening, pathological biopsy and imaging examination of clinical studies to 
confirm the baseline evaluation before enrollment. 
(3) Study group and treatment: After initial screening according to the inclusion and exclusion criteria, 
enrollment after signing the informed consent form. This study is a single-center, randomized 
phase II exploratory study. Block randomization was used to generate random sequences through 
a central random system. The specific operation is to allocate the subjects who meet the inclusion 
criteria to the short-course treatment group or the long-course treatment group in a ratio of 1:1, 
and the randomization form is generated by an independent statistician by a third-party 
randomizer independent of the research team through the Interactive Web Response System 
(IWRS), and the subjects who meet the randomization criteria are randomized through the 
randomization system, and the subjects are given a unique randomization number, which is 
recorded in the case report form (CRF). The block length is dynamic block size to ensure that the 
researcher cannot predict the grouping outcome. At the same time, this study uses blinded 
endpoint evaluation, and during the evaluation of outcome indicators (such as imaging results, 
pathological results, etc.), the evaluators (such as radiologists, pathologists) do not know the 
grouping of the subjects. Short-course group (two cycles): Albumin-bound paclitaxel 260 mg/m2, 
carboplatin AUC=5, and adebelimab 1200 mg intravenously on the first day of each three-week 
course of treatment every three weeks. A total of two cycles were performed, and surgery was 
performed 21 days after the end of the second cycle, and radiotherapy and chemotherapy were 
performed according to the pathological stage after surgery. Patients who did not require 
radiotherapy were maintained with a PD-L1 inhibitor (adebelimab) as a single agent, and patients 

 30 / 37 
 
who required chemoradiotherapy were maintained as a single agent at the same time, and the 
duration of medication for all patients was one year (from the time of the first dose at the initial 
diagnosis to the time of the last dose after surgery). Long-course group (3 cycles): Intravenous 
albumin-bound paclitaxel 260 mg/m2, carboplatin AUC=5, and adebelimab 1200 mg on the first 
day of each 3-week course every three weeks. A total of three cycles were performed, and surgery 
was performed 21 days after the end of the third cycle, and radiotherapy and chemotherapy were 
performed according to the pathological stage after surgery. Patients who did not require 
radiotherapy were maintained with a PD-L1 inhibitor (adebelimab) as a single agent, and patients 
who required chemoradiotherapy were maintained as a single agent at the same time, and the 
duration of medication for all patients was one year (from the time of the first dose at the initial 
diagnosis to the time of the last dose after surgery). All enrolled patients were given conventional 
medication to prevent vomiting in each cycle, while dexamethasone was given intravenous 
injection before each dose for allergy prevention. 
(4) Visit and follow-up: During the study, you also have some corresponding responsibilities, please 
follow up in our hospital or telephone follow-up after each cycle of treatment, perform blood 
routine, liver and kidney function tests in our hospital or local hospital, and inform the researcher 
of the specific report. Return to our hospital for follow-up consultation 1 month after surgery and 
3 months after surgery according to the doctor's instructions for clinical physical examination. 6 
months after surgery and 1 year after surgery, they need to return to our hospital for MRI 
examination, and then return to our hospital for MRI examination at least once a year. 
(5) Collection and testing of remaining samples: In this study, your doctor will collect your remaining 
blood during routine diagnosis and treatment, as well as some tumor tissue samples from 
preoperative biopsy and postoperative pathology for laboratory or genetic testing after obtaining 
your consent, and the use of these specimens will not affect your disease diagnosis and treatment. 
The results of these tests may help you better understand your disease. 
(6) Other matters that require your cooperation: During the study, you are responsible for reporting to 
your doctor any changes in your physical and mental aspects during the study, regardless of 
whether such changes are related to the study. Be sure to let your doctor know about any other 
medications you are currently using and are being used during the study. During the study, please 

 31 / 37 
 
do not use any other treatment-related chemotherapy or immunological drugs, and if you need 
other treatment, please contact your doctor in advance for formal medical guidance. 
 
5. Alternative treatment 
Participation in this study is completely voluntary, and if you do not participate or opt out at any 
stage of the study, you will receive alternative treatment. Alternative treatments include: surgery, 
chemotherapy, radiation therapy. You and your doctor can discuss specific alternative treatments before 
deciding whether to take part in this study. 
 
6. Expenses related to this study 
The drugs nab-azanol and carboplatin used in this study are the therapeutic drugs recommended 
by clinical guidelines, and imaging, tests and other examinations are routine examination items, so you 
need to bear the cost yourself. Participation in this study will not add an additional financial burden to 
you. The adebelimab used in this study has applied for the corresponding donation subsidy through the 
manufacturer, and the subjects in the short-course group (two cycles) pay one cycle of drug before 
surgery, and then use the drug for free in the second cycle; After paying for one free drug after surgery, 
you will receive 2 free medications, and after paying another time, you will receive free medication for 
1 year (within 1 year from the first dose). Subjects in the long-course group (three cycles) paid for one 
cycle of medication before surgery, and then the second cycle was free of charge. After paying the drug 
in the third cycle, you can receive 2 doses of immune maintenance drugs after surgery, and you can get 
free medication for 1 year after another payment (within 1 year from the first dose). 
 
7. Possible benefits 
Participating in this clinical study, your disease may be remitted, but it may not achieve the 
expected effect, or even disease progression; The treatment and examinations you receive may not 
directly benefit you, but your participation will contribute to further medical research and 
understanding of such diseases, and hopefully improve the diagnosis and treatment of diseases in the 
future. 
 

 32 / 37 
 
8. Possible risks 
Diagnosis and treatment of any disease can bring discomfort and unpredictable risks. 
1. The study protocol causes the subject to have tumor progression and the risk of delaying surgery. 
2. This study protocol has the potential to cause reversible or irreversible damage to liver and kidney 
function. 
3. This regimen may lead to complications after immunotherapy such as immune myocarditis, 
immune pneumonia, and immune neuritis. 
4. This study protocol may lead to post-chemotherapy reactions such as bone marrow suppression, 
gastrointestinal reactions, skin rashes, etc. 
5. The possibility that the study protocol will lead to an increased chance of surgical complications. 
6. Pregnancy risk: Since the effects of the study drug on the fetus and breastfed infants are not known, 
it is important that you cannot be pregnant or breastfeeding at the time of entry into the study, and 
you must not become pregnant during the study. You must not participate in this study if you are 
pregnant, trying to become pregnant, or breastfeeding. If you are a female subject of childbearing 
potential, the study doctor will ask you to provide a urine sample to take a pregnancy test before 
you start the study. If you are a female subject, of childbearing potential, must use a reliable method 
of contraception for the duration of the study. The study doctor will tell you which are acceptable 
methods of birth control. The following methods of contraception are recommended: condoms 
with or without spermicide (a drug that kills sperm), vaginal diaphragm or cervical cap with 
spermicide, or intrauterine device (a small contraceptive device installed in a woman's uterus). 
Emergency contraception taken after unprotected sex, such as emergency contraception, cannot be 
used as a conventional method of contraception. If you find a positive pregnancy test while 
participating in the study, you should inform the study doctor immediately. You will need to stop 
taking the study drug immediately and will need to agree to undergo further follow-up tests. If you 
are confirmed to be pregnant, the study doctor may ask you to withdraw from the study and 
terminate the pregnancy, and you will be responsible for the costs associated with terminating the 
pregnancy; If you choose to continue your pregnancy, it may result in adverse pregnancy outcomes, 
and you will be responsible for the consequences and costs arising therefrom. If you are a male 
subject: Participation in this study may damage your sperm and harm your child during the study. 

 33 / 37 
 
This damage is currently unpredictable. If sexually active, you must agree to use medically 
approved contraception during the course of the study. Medically accepted contraception includes 
surgical contraception (e.g., vasectomy) or spermicidal condoms. Emergency contraception taken 
after unprotected sex, such as emergency contraception, cannot be used as a conventional method 
of contraception. Please inform your partner of the risks of this drug to the unborn baby. She should 
know that if she is pregnant, you need to tell your study doctor immediately, and she should tell 
her doctor immediately and agree to further follow-up tests. If your partner is confirmed to be 
pregnant, the study doctor may request termination of pregnancy at the expense of you and your 
partner; If your partner chooses to continue the pregnancy, it may result in an adverse pregnancy 
outcome and the consequences and costs will be borne by you and your partner. 
7. The most common adverse reactions of adebelimab are proteinuria, fatigue, elevated corticotropin, 
increased 
aspartate 
aminotransferase, 
elevated 
thyroid-stimulating 
hormone, 
elevated 
hemobilirubin, elevated alanine aminotransferase, anemia, decreased appetite, and rash, which are 
mostly grade 1 or 2 in severity. The most common grade 3 adverse reactions > lung inflammation, 
increased alanine aminotransferase, increased aspartate aminotransferase, increased conjugated 
bilirubin, abnormal liver function, anemia, and hypokalemia. In addition, the most common 
adverse reactions with adebelimab in combination with chemotherapy were leukopenia, 
neutropenia, anemia, elevated alanine aminotransferase, thrombocytopenia, increased aspartate 
aminotransferase, decreased appetite, nausea, elevated Y-glutamyltransferase, fatigue, and 
hypothyroidism. The most common grade 3 adverse reactions > neutropenia, leukopenia, 
thrombocytopenia, anemia, lymphopenia, elevated alanine aminotransferase, and hypertension. 
Other adverse reactions can be found in the drug label for details. 
 
9. Over-explaining the risks of medication 
1. Depending on your condition, the current routine use of clinical drugs is not ideal. After fully 
considering the adverse reactions, contraindications, precautions, etc., and in accordance with the 
principles of beneficial patient health and informed consent, we believe that off-label use of this 
drug is your current best diagnosis and treatment plan.  
2. You have the right to ask the physician or pharmacist to explain the content contained in this 

 34 / 37 
 
informed consent form in plain language, and you have the right to ask questions to the physician 
and pharmacist and get an objective and scientific answer after the physician or pharmacist 
explains.  
3. The use of this drug off-label may cause the following adverse reactions, including but not limited 
to: gastrointestinal symptoms, hematological symptoms, liver function damage and other adverse 
reactions. 
 
10. Study the treatment and compensation of related injuries 
If an adverse event occurs that is indeed caused by the diagnostic tests and treatments required 
for the study drug and the study protocol, and causes harm to you, the doctor will provide you with 
active treatment. This study has purchased insurance, and if there is any research-related damage, 
the center will bear the relevant medical expenses and compensation costs in accordance with the 
law. 
 
11. Confidentiality measures 
The results of this clinical study are only used for scientific purposes, so your participation in 
the study and your personal information during the study will be confidential and will be protected 
in accordance with legal regulations, and your name and identity will not be disclosed, and your 
name will not appear in any research reports and public publications. Government management 
departments, hospital ethics committees, researchers, etc. have the right to access all your research 
materials, including clinical observation sheets, trial data, etc. according to regulations due to work 
needs. 
 
12. Termination of research 
    You can withdraw from the study at any time without a reason while participating in the study, 
and your decision will not have any impact on your continued medical treatment. Your doctor may 
also stop you from continuing to participate in the study for the following reasons: 
You did not take medication as instructed and requested by the study doctor; 
Disease progression or intolerable adverse reactions, and the study doctor believes that continuing 

 35 / 37 
 
to participate in the study will cause harm to you; 
You have received treatment that is not allowed in this study; 
・The research doctor, ethics committee, or government administration requested the study to be 
stopped. 
When you withdraw from the study or the study is terminated, the study doctor will discuss follow-
up treatment with you. 
 
13. Rights 
This clinical study has been reviewed and approved by the Medical Ethics Committee of Sun 
Yat-sen Memorial Hospital of Sun Yat-sen University, and the protocol design meets ethical 
requirements, which will ensure that your rights and interests are not infringed upon in this study. 
Your participation in this clinical study is completely voluntary, and you may refuse to 
participate or withdraw at any time without discrimination or retaliation, and your medical treatment 
and rights will not be affected. If you withdraw from a clinical study, you should complete some 
appropriate medical tests at the time of withdrawal for safety reasons. If the doctor deems you 
unsuitable to continue participating during the study, the doctor has the right to decide to suspend 
your continued participation in this clinical study in order to protect your interests. In addition, you 
can stay informed about your research during your research. You will also be notified if we have 
some updates on this study so that you can decide whether to continue with the study. 
During the clinical study, please notify your research doctor immediately if you experience any 
discomfort or worsening of your condition, and we will take appropriate medical measures in a 
timely manner. If you comply with study protocol regulations, the investigator will actively treat 
study-related adverse events that occur. 
 
14. Detailed contact information 
If you have any concerns or questions about your participation in this study, or if you experience 
any unusual reactions while participating in this study, or in the event of an emergency, you should 
contact: 
Doctor: Huang Zhiquan Contact number: 13826142898 

 36 / 37 
 
Doctor: He Yilin Contact number: 13680281880 
If you have any complaints or concerns or questions about the way the study physician conducts 
the study, as a study subject, you can contact the Medical Ethics Committee of the Center: 
Email: sysyxllwyh@163.com Contact number: 020-81332587 
 
Informed consent form • consent signature page 
Study participant statement 
I have read the informed consent form carefully, the researchers have explained it to me in 
detail and answered my questions, and I am fully aware of the following: 
（1） As a study participant, I will comply with the requirements for study participants, voluntarily 
participate in this study, and fully cooperate with the research staff to truthfully and objectively 
provide the researchers with their health status and related information before participating in 
this study. 
（2） I agree to Sun Yat-sen Memorial Hospital's access to my medical information and research 
results for the purpose of scientific research. I understand that the results of this study will only 
be used for scientific research purposes, except for government administrations, ethics 
committees, researchers, etc., and my personal information participating in the research and 
research will be confidential and will be protected in accordance with the law. 
（3） I volunteer to participate in this study and will be properly and aggressively treated if there are 
study-related adverse reactions in the study. 
（4） My participation in this study is completely voluntary, and I can refuse to participate or 
withdraw from the study at any time without discrimination or retaliation, and my medical 
treatment and rights will not be affected. 
At the same time I declare: 
（1） 
I am willing to comply with the research process; 
（2） 
During the study, I am willing to cooperate with the doctor to see a doctor within the 
specified time and do corresponding examinations; 
（3） 
This informed consent form has been received. 
 

 37 / 37 
 
Study participant signature:  
     
Contact:  
    
Signing Date:  
 
If the study participant is a person with no or limited civil capacity (minors under 18 years of age, unconscious 
or for various reasons resulting from a thought disorder that prevents them from signing the informed consent form), 
their guardian is requested to sign here: 
Signature of the guardian: 
 
 
Relationship with Study Participants: Contact: 
Signing Date:  
 
If the study participant/guardian is unable to read and cannot sign the informed consent form, please sign it here 
by an impartial witness : 
Signature of an impartial witness:  
 
    Contact:  
    
Signing Date:  
 
 
 
Statement by the researcher 
I myself have fully explained and explained the purpose, research methods, operating 
procedures, and possible risks and potential benefits of this study to the study participants, and 
answered all relevant questions of the study participants satisfactorily. 
Signature of the investigator (who informs the study participant): 
 
        Contact: 
 
 
Signing Date: