Toripalimab Plus Induction Chemotherapy Followed by Radiation Therapy Combined With Omega-3 for Locally Advanced Nasopharyngeal Carcinoma: A Phase II, Single Arm Clinical Trial
Phase: PHASE2
Conditions: Nasopharyngeal Carcinoma (NPC)
Sponsor: Affiliated Hospital of Guangdong Medical University

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Clinical research project of Guangdong
Medical University Affiliated Hospital
Research programmes
Project Name
(Chinese)
Toripalimab Plus Induction Chemotherapy Followed by
Radiation Therapy Combined with Omega-3 for Locally
Advanced Nasopharyngeal Carcinoma: A phase II, single
arm clinical trial
Project Name
(English)
Toripalimab Plus Induction Chemotherapy Followed by
Radiation Therapy Combined with Omega-3 for Locally
Advanced Nasopharyngeal Carcinoma: A phase II, single
arm clinical trial
Research Unit
Affiliated Hospital of Guangdong Medical University
Research Lead
Luo Haiqing
Version Number
2.0
Version Date
June 27,2025
Duration of Study
June 2025 to December 2029

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Research programme
Project Name
Toripalimab Plus Induction Chemotherapy Followed by Radiation
Therapy Combined with Omega-3 for Locally Advanced
Nasopharyngeal Carcinoma: A phase II, single arm clinical trial
Lead Researcher
Luo Haiqing
contact way
13590386289
Source of Funds
Self-financing
Funded funds
(ten thousand)
not have
abstract
Type of Test Design
observational study
Research Center
Single Centre
Randomized Grouping
NA
Blind Method
NA
Type of study
optimal efficiency
Purpose of Research
1. Main Objective: This study will demonstrate the 2-year PFS
rate of trypirizumab + induction chemotherapy sequential
radiotherapy combined with OMEGA-3 in locally advanced
nasopharyngeal carcinoma.
2. Secondary research objectives: This study will clarify the ORR,
OS, adverse reactions, nutritional status analysis and quality of life
analysis of local advanced nasopharyngeal carcinoma treated with
trypirizumab + induction chemotherapy sequential radiotherapy +
OMEGA-3.
Study
Endpoint/Observation
Endpoint
1. Primary study endpoint: 2-year PFS.
2. Secondary study endpoints: ORR, OS, adverse reactions,
nutritional status analysis, quality of life analysis.
Exploratory endpoints:(1) to explore the correlation between

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cytokines and patient prognosis; (2) to explore the correlation
between OMEGA-6/OMEGA-3 ratio and patient efficacy; (3) to
explore the correlation between immune cell changes in tumor
microenvironment and anti-tumor activity of the study protocol.
Study Population
Patients aged 18 to 65 years with pathological diagnosis of
nasopharyngeal carcinoma and stage anyTN2-3M0 or T4N1M0
(AJCC8th/UICC staging) were selected from those hospitalized in
the Affiliated Hospital of Guangdong Medical University between
2025 and 2026.
Diagnostic Criteria
Pathological diagnosis was nasopharyngeal carcinoma with
anyTN2-3M0 or T4N1M0 stage locally advanced nasopharyngeal
carcinoma (AJCC8th).
Inclusion Criteria
1. Can provide written informed consent and understand and
follow the research requirements and assessment schedule.
2. Age between 18 and 65 years (or the legal age specified by
local laws governing the study) at the date of signing the informed
consent form.
3. Pathological diagnosis was nasopharyngeal nonkeratinizing
carcinoma (differentiated or undifferentiated, i.e., WHO type II or
III).
4. Clinical stage is anyTN2-3M0 or T4N1M0 (AJCC8th/UICC
staging).
5.ECOG score 0-1.
6. Hemoglobin (HGB) ≥90g/L, white blood cell (WBC) ≥4.0
×109/L, platelet (PLT) ≥100×109/L.
7. Liver function: ALT and AST <2.5 times the upper limit of
normal value (ULN), total bilirubin <2.0×UL, serum albumin ≥
28g/L.
8. Renal function: serum creatinine <1.5×ULN or calculated

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creatinine clearance rate (CrCl) ≥60mL/min (Cockcroft-Gault
formula).
9. Thyroid-stimulating hormone (TSH) ≤1×ULN (if abnormal,
FT3 and FT4 levels should be examined at the same time. If FT3
and FT4 levels are normal, participants can be enrolled).
10. International Standardized Ratio (INR) and activated partial
thromboplastin time (APTT) ≤1.5×ULN (unless the subject is
receiving anticoagulant therapy and the coagulation parameters
(PT/INR and APTT) are within the expected range for
anticoagulant therapy at screening).
Exclusion criteria
1. Patients with recurrent and distant metastatic nasopharyngeal
carcinoma.
2. Pathology was keratinizing squamous cell carcinoma (WHO
type I).
3. Patients who have undergone radiotherapy or systemic
chemotherapy.
4. Pregnant or lactating women who are of childbearing age and
have not taken effective contraceptive measures.
5.HIV positive.
6. Had other malignancies (except cured basal cell carcinoma or
cervical carcinoma in situ).
7. Patients who have received immunomodulatory inhibitors
(CTLA-4, PD-1, PD-L1, etc.) therapy.
8. Patients with immunodeficiency diseases and history of organ
transplantation.
9. Patients who received high doses of glucocorticoids, anticancer
monoclonal antibodies, or other immunosuppressants within 4
weeks.
10. Patients with significantly impaired heart, liver, lung, kidney
and bone marrow function.
11. Use of other investigational drugs or participation in other
clinical trials.

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12. Refuse or be unable to sign the informed consent form for
participation in the trial.
13. Persons with personality or mental illness, without capacity
for civil conduct or limited capacity for civil conduct.
14. Hepatitis B surface antigen (HBsAg) positive and peripheral
blood hepatitis B virus deoxyribonucleic acid (HBVDNA) ≥
1000cps/ml.
15.HCV Patients with positive antibody test results can only be
included in this study when the polymerase chain reaction of
HCVRNA is negative.
16. Patients with any serious bleeding event of grade 3 or higher
in CTCAEv5.0 within 4 weeks prior to screening and who are
judged by the investigator to be at high risk of bleeding.
17. Venous/arterial thrombosis events occurred within 6 months
prior to screening, such as cerebrovascular accident (including
transient ischemic attack, cerebral hemorrhage, cerebral
infarction), deep vein thrombosis and pulmonary embolism.
18. Patients with hypertension that cannot be reduced to the
normal range by antihypertensive drugs (systolic blood pressure
≥140mmHg or diastolic blood pressure ≥90mmHg; based on the
average of BP readings obtained from ≥2 measurements) who
have previously experienced hypertensive crisis or hypertensive
encephalopathy.
19. History or current inflammatory bowel disease (e.g., Crohn's
disease, ulcerative colitis, or chronic diarrhea); history of previous
or current gastrointestinal perforation and/or fistula.
20. Known history of active tuberculosis (TB). Subjects suspected
of having active TB should be examined for chest X-ray, sputum,
and clinical symptoms and signs.
21. Other serious, uncontrolled medical conditions and infections
or other contraindications for treatment, or any condition that the
investigator considers to be likely to cause risks in the
administration of the study drug, or to interfere with the
evaluation of the study drug, the safety of the subject or the

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interpretation of the results.
Exit criteria
1. According to RECISTv1.1 criteria, it is considered as imaging
disease progression;
2. The patient's written consent is revoked;
3. There are any medical conditions identified by the investigator
that may endanger the safety of the patient if the patient continues
to receive the study treatment;
4. Concurrent use of any anti-tumor therapy (i.e., chemotherapy,
hormone therapy, immunotherapy, or standard or trial drugs
[including Chinese herbal medicine and proprietary Chinese
medicine] for the treatment of cancer);
5. Poor patient compliance;
Sample Capacity
To increase the 2-year PFS from 71% to 96%, we used
PASS15 software and adopted the Z-test with a=0.05 (two-sided
test) and β=0.10. The calculated sample size was 24 patients.
Considering a 20% dropout rate, at least 30 patients were required
to be enrolled.

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Research Factors
Interventions in this study:
①Induction therapy: Toripalimab 240mg d1 + paclitaxel
(albumin-bound) 260mg/m2 d1 + cisplatin 80mg/m2 d2 Q3W X 3
cycles
②Radiotherapy: IMRT +Toripalimab 240mg Q3W X 3 cycles +
omega-3 (6 tablets qd during radiotherapy)
IMRT：GTVnx 69.96Gy，GTVnd 69.96Gy，CTV1 60Gy，CTV2
54Gy
③Maintenance therapy: Toripalimab 240mg Q3W for 6 cycles
Evaluating Indicator
2-y-PFS, ORR, OS, adverse reactions, nutritional status analysis,
quality of life analysis.

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Follow-Up
1. During treatment: After the start of the study protocol, clinical
observation should be strictly carried out. The occurrence and
classification of adverse events and adverse reactions should be
evaluated weekly according to NCICTCAEv5.0 version. Blood
routine and blood biochemical should be monitored every 3
weeks. Concurrently, combined medication and adverse events
(including adverse events of intravenous medication and
chemoradiotherapy) should be recorded during the clinical study.
2. Conduct efficacy and safety evaluations after treatment
completion, including 2-year progression-free survival (2y-PFS),
objective response rate (ORR), complete blood count (CBC),
biochemical parameters, EB virus DNA quantification, thyroid
function tests, serum amylase and lipase levels, electronic
nasopharyngoscopy, enhanced nasopharyngeal-neck MRI, chest
X-rays or CT scans, and abdominal ultrasound or CT. If clinically
significant abnormalities are detected, follow-up examinations
should be repeated until normalization. Near-term follow-up
evaluations should be conducted three months post-treatment,
while long-term follow-ups should occur every six months after
treatment initiation. Monitoring methods include recording
patients' return-to-hospital review data, physician-signed
mail/telephone follow-ups, etc., to assess treatment efficacy,
recovery of toxic reactions, and both short-term and long-term
toxicity profiles. Follow-up protocols shall adhere to the clinical
guidelines for individual disease management.
Statistical Analysis
The research data were processed using SPSS26.0 statistical
software. In the univariate analysis of collected data, continuous
measurement data were presented as mean ± standard deviation,
categorical data as frequency, and measurements with normal
distribution were analyzed using t-tests. Categorical data were
statistically evaluated through Pearson's chi-square test or Fisher's
exact test. Significant covariates were controlled during grouping
and adjusted in subsequent analyses. All statistically significant risk
factors underwent multivariate analysis via logistic regression.
Survival analysis utilized Kaplan-Meier method and log-rank test.
Statistical significance was defined as P values <0.05.
Research Findings
1. Publish an SCI paper.
2. Train a graduate student.

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1. Basis of the topic
1.1 Research significance
Nasopharyngeal carcinoma (NPC), a malignant tumor originating from the
nasopharyngeal mucosa, exhibits distinct geographical distribution patterns,
primarily affecting populations in southern China and Southeast Asia[1].
According to the World Health Organization's classification system, NPC is
categorized into three histological subtypes: squamous cell carcinoma,
non-squamous cell carcinoma, and basaloid squamous cell carcinoma.
Non-squamous NPC is further subdivided into differentiated and undifferentiated
subtypes[2]. Notably, over 95% of NPC cases in high-incidence regions present as
non-squamous undifferentiated subtypes, which exhibit aggressive biological
behavior and predispose patients to distant metastasis[3]. Additionally, the
carcinogenic effects of non-squamous undifferentiated NPC are closely associated
with chronic latent infections caused by Epstein-Barr virus (EBV)[4].
Given the anatomical complexity of the nasopharynx and its radio-sensitivity,
radiation therapy forms the cornerstone of treatment for non-metastatic
nasopharyngeal carcinoma. The advent of Intensity-Modulated Radiotherapy
(IMRT) has revolutionized this approach by enabling precise tumor targeting with
minimal impact on adjacent tissues. For early-stage patients receiving IMRT alone,
both the 5-year local recurrence-free survival (LRFS) and distant metastasis-free
survival (DMFS) rates exceed 95%[5].
However, for patients with locally advanced nasopharyngeal carcinoma, the
adverse characteristics of the common undifferentiated pathological subtype and
the inherent advanced stage at diagnosis increase the risk of treatment failure. The
5-year overall survival (OS) rate for nasopharyngeal carcinoma patients receiving
only local radiotherapy is below 50%[6,7]. Furthermore, with significant
improvements in diagnostic and radiotherapy techniques that have greatly
enhanced local control rates, distant metastasis has become the primary cause of
treatment failure[8]. In recent years, extensive research has focused on combining

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systemic chemotherapy with radiotherapy to improve survival rates in advanced
nasopharyngeal carcinoma patients. Additionally, the use of concurrent
chemoradiotherapy (CCRT) combined with induction chemotherapy (IC) or
adjuvant chemotherapy (AC) has significantly improved clinical outcomes.
Nasopharyngeal carcinoma tissues exhibit unique immunological features,
including dense stromal immune infiltration[9], immunosuppressive
characteristics[10], and high expression of programmed cell death ligand 1
(PD-L1)[11]. These features indicate that immune checkpoint inhibitors could
serve as a promising therapeutic strategy for nasopharyngeal carcinoma.
Three Phase III clinical trials have demonstrated that combining PD-1
immunosuppressants with gemcitabine (GP) chemotherapy as first-line therapy can
significantly extend progression-free survival (PFS)[12-14] in patients with R/M
nasopharyngeal carcinoma. Current research is exploring the combination of PD-1
immunosuppressants and chemoradiotherapy for locally advanced nasopharyngeal
carcinoma. Several Phase II trials have shown promising responses, survival
outcomes, or both, when anti-PD-1 or anti-PD-L1 inhibitors were added during or
throughout treatment regimens including IC, AC, IC+AC, or the entire course of
therapy (objective response rate 88.9%-94.4%; 2-year PFS rate
69.6%-91.8%)[15-18]. To date, the only large-scale Phase III trial with published
data evaluated PD-1 immunosuppressant efficacy in locally advanced
nasopharyngeal carcinoma. Results indicated that adding sintilimab during GPIC,
CCRT, or as adjuvant therapy significantly reduced recurrence or mortality risks in
high-risk patients, with a 10% increase in 3-year event-free survival ([19]).
Additionally, sintilimab-treated groups showed marked reductions in distant
metastasis and local recurrence risks (3-year disease-free survival rate: 90.3% vs.
82.8%, HR0.57 [95% CI 0.33–0.98], p=0.039; 3-year local recurrence-free
survival rate: 93.4% vs. 86.8%, HR0.52 [95% CI 0.27–0.97], p=0.038). Notably,
no significant differences in quality of life were observed between the two groups.
These findings indicate that PD-1 immunotherapy combined with

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chemoradiotherapy could establish a new standard of care for high-risk patients
with locally advanced nasopharyngeal carcinoma. Furthermore, ongoing clinical
trials are evaluating the efficacy and safety of various immune checkpoint
inhibitors (ICBs) in combination with chemoradiotherapy during induction,
adjuvant phases, or as an alternative to conventional chemotherapy for locally
advanced nasopharyngeal carcinoma. The results may advance our understanding
of optimal sequencing and regimens for integrating immunotherapy with
chemoradiotherapy in current nasopharyngeal carcinoma management.
Omega-3 polyunsaturated fatty acids (OEMG-3PUFAs) are essential fatty
acids that the human body cannot synthesize, primarily found in plant oils and fish
fats. DHA and EPA, two key components of OEMG-3PUFAs, have been
extensively studied as the most researched types of this family. These fatty acids
play a role in preventing cardiovascular diseases, regulating inflammation, and
improving nutritional status[20]. Research by Mocellin et al. demonstrated that
OEMG-3PUFAs can increase plasma albumin and prealbumin levels in gastric
cancer patients[21][21].My research shows that omega-3PUFAs can reduce CRP
levels and shorten the duration of systemicinflammatoryresponsesyndrome (SIRS)
[22].Meta analysis showed that omega-3PUFAs could improve the nutritional
status of patients after gastrectomy and reduce inflammatory indicators such as
C-reactive protein (CRP) and interleukin 6 (IL-6) [23].In a recent study of 37
postoperative head and neck cancer patients who took two to three cans of
Omega-3FA and arginine enhancement supplements daily for 12 weeks, the results
showed improvements in albumin, prealbumin, transferrin, and lymphocyte levels
in the enhancement group [25].In head and neck cancer and esophageal cancer
patients undergoing radiochemotherapy (RCT), formulations containing Omega-3
fatty acids have demonstrated equivalent therapeutic benefits. A randomized
controlled trial involving 37 patients evaluated the efficacy of an
immunomodulatory diet combining arginine, omega-3 fatty acids, and
nucleotide-rich nutrients. Results showed that enteral nutrition group patients

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exhibited significant improvements in overall body weight, elevated albumin levels,
and enhanced plasma antioxidant capacity. While functional capacity measured by
WHO Performance Status and Karnofsky Index remained stable in the
immunomodulatory group, it markedly declined [26] in standard enteral nutrition
recipients. In 31 non-metastatic stage III/IV head and neck squamous cell
carcinoma patients receiving radiochemotherapy, another oral supplement
containing amino acids, omega-3 fatty acids, nucleotides, vitamins, and
antioxidants demonstrated poorer efficacy in modulating pro-inflammatory,
proangiogenic, and pro-oxidative states [27].[24]
Early enteral nutrition intake of large amounts of Omega-3 fatty acids can
effectively reduce platelet aggregation, coagulation activity and the production of
cytokines. Clinical manifestations include decreased body temperature and
significantly reduced biochemical indexes such as plasma IL-8 levels, which
confirm the anti-inflammatory effect of Omega-3 fatty acids [28].The above
reaction was improved by adding RNA and arginine to the formula [29].In the
Omega-3FA supplementation group, inflammation and immune function improved
postoperatively. The Omega-3FA group showed significantly reduced serum
procalcitonin levels and elevated CD4+/CD8+ cell ratio on day 6 post-surgery,
though no significant differences were observed on days 1 and 3[30]. Generally,
these Omega-3 fatty acid-containing formulas can be safely used in sepsis patients,
but there is insufficient evidence to recommend routine immunomodulatory
nutrition for esophageal cancer surgery patients[31]. A Phase III double-blind trial
of immunomodulatory nutritional formula during adjuvant chemoradiotherapy for
head and neck cancer patients revealed that ITT analysis over three years after
adjuvant chemoradiotherapy showed no significant survival improvement in the
immunomodulatory nutrition formula group.However, in patients with ≥75%
compliance, compared with the control group, the immunomodulatory nutritional
formula group showed a significant improvement in [32] at 3y OS and 3y PFS
(P<0.05).

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The current standard treatment for high-risk locally advanced nasopharyngeal
carcinoma involves induction chemotherapy followed by concurrent
chemoradiotherapy and adjuvant chemotherapy. However, this regimen causes
significant adverse reactions in patients, with some still experiencing recurrence or
metastasis. With the emergence of immunotherapy, it has become a first-line
treatment for advanced nasopharyngeal carcinoma, particularly in high-risk locally
advanced cases. Omega-3, known for its anti-inflammatory and antitumor
mechanisms, has been shown to alleviate radiochemotherapy side effects and
enhance therapeutic efficacy. This study innovatively removes concurrent
chemotherapy during chemoradiotherapy for high-risk locally advanced
nasopharyngeal carcinoma, replacing it with concurrent immunotherapy combined
with Omega-3 supplementation. This approach aims to improve treatment
outcomes while reducing adverse reactions in such high-risk cases.
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patients undergoing radiochemotherapy: a randomized clinical trial [J]. Clin Nutr, 2014,
33(2): 204-10.
[27]
[27]
Machon C, Thezenas S, Dupuy A M, [27]Machon C, Thezenas S, Dupuy A M,
et
al. Immunonutrition before and during radiochemotherapy: improvement of inflammatory
parameters in head and neck cancer patients [J]. Support Care Cancer, 2012, 20(12):
3129-35.
[28]
[28]
Aiko S, Yoshizumi Y, Tsuwano S, [28]
Aiko S, Yoshizumi Y, Tsuwano S,
et al.
The effects of immediate enteral feeding with a formula containing high levels of omega-3
fatty acids in patients after surgery for esophageal cancer [J]. JPEN J Parenter Enteral Nutr,
2005, 29(3): 141-7.
[29]
[29]
Aiko S, Yoshizumi Y, Ishizuka T, [29]
Aiko S, Yoshizumi Y, Ishizuka T,
et al.
Enteral immuno-enhanced diets with arginine are safe and beneficial for patients early
after esophageal cancer surgery [J]. Dis Esophagus, 2008, 21(7): 619-27.
[30]
[30]
Long H, Yang H, Lin Y, [30]
Long
H,
Yang
H,
Lin
Y,
et
al.
Fish
oil-supplemented parenteral nutrition in patients following esophageal cancer surgery:
effect on inflammation and immune function [J]. Nutr Cancer, 2013, 65(1): 71-5.
[31]
[31]
Mudge L, Isenring E, Jamieson G G. Immunonutrition in patients undergoing
esophageal cancer resection [J]. Dis Esophagus, 2011, 24(3): 160-5.
[32]
[32]
Boisselier P, Kaminsky M C, Thézenas S, et al. A double-blind phase III trial of
immunomodulating nutritional formula during adjuvant chemoradiotherapy in head and
neck cancer patients: IMPATOX [J]. Am J Clin Nutr, 2020, 112(6): 1523-31.
2. Research content
2.1 Research Purpose
The main purpose of this study was to clarify the 2-year PFS rate of

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toripalimab + induction chemotherapy sequential radiotherapy combined with
OMEGA-3 in locally advanced nasopharyngeal carcinoma.
Secondary objectives of the study: to clarify the ORR, OS, adverse reactions,
nutritional status and quality of life analysis of local advanced nasopharyngeal
carcinoma
treated
with
toripalimab
+
induction
chemotherapy
sequential
radiotherapy combined with OMEGA-3.
2.2 Research significance
Nasopharyngeal carcinoma, also known as "Guangdong cancer", exhibits
unique epidemiological characteristics with significant regional, ethnic, and gender
variations in prevalence. Distinct from other cancers, its geographical distribution
is highly uneven, which stands out as one of its most prominent features.
According to data from the International Agency for Research on Cancer (IARC),
there were approximately 133,000 new cases of nasopharyngeal carcinoma
globally in 2020, accounting for 0.7% of all newly detected tumors. Over 70% of
these cases occurred in East and Southeast Asia, particularly in South China. In
2018, China's nasopharyngeal carcinoma incidence rate (calculated using global
age-standardized methods) reached 3 per 100,000 population, far exceeding
Europe's 0.4 per 100,000. The current standard treatment for high-risk locally
advanced nasopharyngeal carcinoma involves induction chemotherapy followed by
concurrent chemoradiotherapy and adjuvant chemotherapy. However, treatment
outcomes remain suboptimal with significant adverse reactions in these patients.
Therefore, developing more effective and less toxic treatment regimens has
become an urgent priority. This Phase II single-arm clinical study aims to
preliminarily evaluate the efficacy, adverse reactions, nutritional status analysis,
and quality of life assessment of triple therapy combining toripalimab, induction
chemotherapy, sequential radiotherapy, and OMEGA-3 supplementation in treating
locally advanced nasopharyngeal carcinoma, providing new reference criteria for
clinical practice.
2.3 Research endpoint (or evaluation indicator)
2.3.1 Main endpoint (or main evaluation indicator) and definition
2-year progression-free survival (2-year-PFS): The probability of no disease
progression or death from any cause within two years from the randomized date to
the first objective record of disease progression, as assessed according to

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RECISTv1.1.
2.3.2 Secondary endpoints (or secondary evaluation indicators) and their
definitions
(1) Overall survival (OS): The period from the random date to the date of death for
any reason.
(2) Objective Response Rate (ORR): The percentage of patients achieving
complete or partial remission, assessed by an independent review committee based
on all randomized patients with measurable disease at baseline according to
RECISTv1.1.
(3) The incidence and severity of adverse events after treatment were graded
according to the common Terminology Standard for Adverse Events v5.0 of the
National Cancer Institute.
(4) Health-related quality of life: assessed using the European Organization for
Cancer Research and Treatment's 35-module head and neck cancer quality of life
questionnaire and core 30, as shown in the patient-reported outcomes.
(5) Nutritional status analysis: regular measurement of weight, etc.
2.3.3. Exploratory endpoints:
(1) Explore the correlation analysis between cytokines and patient prognosis;
(2) Explore the correlation analysis between n6/n3 ratio and patient efficacy;
(3)
Explore
the
correlation
between
immune
cell
changes
in
tumor
microenvironment and anti-tumor activity
3. Research design
3.1 Overall design of the study
This study was a phase II, single-arm intervention clinical study
3.2 The expected schedule and completion date of the research project
June 2025 to December 2029
3.3 Brief test flow chart
Clinical research flow chart

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4. Recruitment of research subjects
Patients aged 18 to 65 years with pathological diagnosis of nasopharyngeal
carcinoma and stage anyTN2-3M0 or T4N1M0 locally advanced nasopharyngeal
carcinoma (AJCC8th) were selected from those hospitalized in the Affiliated
Hospital of Guangdong Medical University between 2025 and 2029.

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4.1 Selection criteria:
1. Can provide written informed consent and understand and follow the research
requirements and assessment schedule.
2. Age between 18 and 65 years (or the legal age specified by local laws of the
study) at the date of signing the INFORMED consent form.
3.
Pathological
diagnosis
was
nasopharyngeal
nonkeratinizing
carcinoma
(differentiated or undifferentiated, i.e., WHO type II or III).
4. Clinical stage is anyTN2-3M0 or T4N1M0 (8thAJCC/UICC staging)
5.ECOG score 0-1.
6. Hemoglobin (HGB) ≥90g/L, white blood cell (WBC) ≥4.0×109/L, platelet
(PLT) ≥100×109/L.
7. Liver function: ALT and AST <2.5 times the upper limit of normal value (ULN),
total bilirubin <2.0×UL, serum albumin ≥28g/L.
8. Renal function: serum creatinine <1.5×ULN or calculated creatinine clearance
rate (CrCl) ≥60mL/min (Cockcroft-Gault formula).
9. Thyroid-stimulating hormone (TSH) ≤1×ULN (if abnormal, FT3 and FT4
levels should be examined at the same time. If FT3 and FT4 levels are normal,
participants can be enrolled).
10. International Standardized Ratio (INR) and activated partial thromboplastin
time (APTT) ≤1.5×ULN (unless the subject is receiving anticoagulant therapy
and the coagulation parameters (PT/INR and APTT) are within the expected range
for anticoagulant therapy at screening).
4.2 Exclusion criteria:
1. Patients with recurrent and distant metastatic nasopharyngeal carcinoma.
2. Pathology was keratinizing squamous cell carcinoma (WHO type I).
3. Patients who have undergone radiotherapy or systemic chemotherapy.
4. Pregnant or lactating women who are of childbearing age and have not taken
effective contraceptive measures.
5.HIV positive.

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6. Had other malignancies (except cured basal cell carcinoma or cervical
carcinoma in situ).
7. Patients who have received immunomodulatory inhibitors (CTLA-4, PD-1,
PD-L1, etc.) therapy.
8. Patients with immunodeficiency diseases and history of organ transplantation.
9. Patients who received high doses of glucocorticoids, anticancer monoclonal
antibodies, or other immunosuppressants within 4 weeks.
10. Patients with significantly impaired heart, liver, lung, kidney and bone marrow
function.
11. Use of other investigational drugs or participation in other clinical trials.
12. Refuse or be unable to sign the informed consent form for participation in the
trial.
13. Persons with personality or mental illness, without capacity for civil conduct or
limited capacity for civil conduct.
14. Hepatitis B surface antigen (HBsAg) positive and peripheral blood hepatitis B
virus deoxyribonucleic acid (HBVDNA) ≥1000cps/ml.
15.HCV Patients with positive antibody test results can only be included in this
study when the polymerase chain reaction of HCVRNA is negative.
16. Patients with any serious bleeding event of grade 3 or higher in CTCAEv5.0
within 4 weeks prior to screening and who are judged by the investigator to be at
high risk of bleeding.
17. Venous/arterial thrombosis events occurred within 6 months prior to screening,
such as cerebrovascular accident (including transient ischemic attack, cerebral
hemorrhage, cerebral infarction), deep vein thrombosis and pulmonary embolism.
18. Patients with hypertension that cannot be reduced to the normal range by
antihypertensive drugs (systolic blood pressure ≥140mmHg or diastolic blood
pressure ≥90mmHg; based on the average of BP readings obtained from ≥2
measurements)
who
have
previously
experienced
hypertensive
crisis
or
hypertensive encephalopathy.
19. History or current inflammatory bowel disease (e.g., Crohn's disease, ulcerative
colitis, or chronic diarrhea); history of previous or current gastrointestinal
perforation and/or fistula.

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20. Known history of active tuberculosis (TB). Subjects suspected of having active
TB should be examined for chest X-ray, sputum, and clinical symptoms and signs.
21. Other serious, uncontrolled medical conditions and infections or other
contraindications for treatment, or any condition that the investigator considers to
be likely to cause risks in the administration of the study drug, or to interfere with
the evaluation of the study drug, the safety of the subject or the interpretation of
the results.
4.3 Time when the subjects participated in the study
Study time (days) = (last hospitalization date-enrollment date) +1
4.4 Recruitment process
Launch time: 2025.06.01
(1) Recruitment plan: Determine the person in charge of recruitment, and discuss
the responsibilities and procedures of recruiting subjects.
(2) Materials for recruiting subjects: Before recruiting subjects, reasonable
recruitment materials should be formulated and submitted to the hospital ethics
committee.
(3) The way of recruiting subjects: Directly recruit from the clinical medical
process, preliminarily determine whether they meet the inclusion criteria of the
trial through the attending physician, and add them to the trial after obtaining the
consent of the volunteers.
(4) Recruitment begins: Meet with volunteers, introduce the contents of the
informed consent form in detail, and inform them to give a reply within one week
before the screening date. If they are willing, they will sign the informed consent
form. Researchers should answer volunteers' questions in detail and be realistic
without unilateral inducement.
(5) Recruitment end: 30 people are expected to be recruited.
4.5 Exit and termination criteria
1. According to RECISTv1.1 criteria, it is considered as imaging disease
progression;
2. The patient's written consent is revoked;
3. There are any medical conditions identified by the investigator that may
endanger the safety of the patient if the patient continues to receive the study
treatment;

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4. Concurrent use of any anti-tumor therapy (i.e., chemotherapy, hormone therapy,
immunotherapy, or standard or trial drugs [including Chinese herbal medicine and
proprietary Chinese medicine] for the treatment of cancer);
5. Poor patient compliance;
5. Study treatment groups
uninvolved
5.1 Randomized grouping
uninvolved
5.1.1 Methods for generating random sequence allocation
uninvolved
5.1.2 Hidden randomization
uninvolved
5.1.3 Blind method and blind lifting
uninvolved
6. Research procedures
6.1 Research treatment period
①Induction therapy: Toripalimab 240mg d1 + paclitaxel (albumin-bound)
260mg/m2 d1 + cisplatin 80mg/m2 d2 Q3W X 3 cycles
②Radiotherapy: IMRT + Toripalimab 240mg Q3W for 3 cycles +
omega-3 (6 tablets qd during radiotherapy). IMRT: GTVnx 69.96Gy, GTVnd
69.96Gy, CTV1 60Gy, CTV2 54Gy
③Maintenance therapy: Toripalimab 240mg Q3W for 6 cycles
6.2 Supply of research-based drugs/treatment
Paclitaxel (albumin-bound) : Dispensed from the hospital central pharmacy
Cisplatin injection: dispensed from the hospital central pharmacy
Toripalimab: supplied by Shanghai Junshi Biomedical Technology Co., LTD
Omega-3 nutritional preparation (Omega-3 soft capsules): provided by this clinical
research project
6.3 Administration, storage and dose adjustment
Paclitaxel (albumin-bound) : 260 mg/m2 intravenous infusion
Cisplatin injection: 80mg/m2 intravenous infusion
Toripalimab injection: 240mg intravenous infusion

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Omega-3 nutritional preparation (Omega-3 soft capsules): 6 capsules orally
6.4 Accompanying treatment and follow-up visits
The use of immune regulatory point (CTLA-4, PD-1, PD-L1, etc.) inhibitors
and other fatty acid nutrients is prohibited
6.5 Patient compliance and withdrawal
Professional oncologists will popularize relevant knowledge to patients and
improve compliance.
7. Sample size estimation
To increase the 2-year PFS from 71% to 96%, we used PASS15 software and
adopted the Z-test with a=0.05 (two-sided test) and β=0.10. The calculated sample
size was 24 patients. Considering the 20% dropout rate, at least 30 patients were
required to be enrolled.
8. Data management and statistical analysis plan
8.1 Data management
(1) Data entry
According to the original observation records of subjects, the researchers shall
load the data into the case report form in a timely, complete, correct and clear
manner and submit them to the clinical research data administrator in a timely
manner.
The data entry shall be carried out by two people with two machines using the
corresponding database system. After that, the database shall be compared twice. If
any problem is found during the process, the researchers shall be notified in time
and asked to give an answer. All kinds of questions and answers exchanged
between them shall be in the form of question sheet, which shall be kept for future
reference.
(2) Contents and methods of data verification and management
After the double input and verification of all case report forms, the data
administrator shall write a database check report, which includes the completion of
the study (including the list of subjects who dropped out), selection/exclusion criteria
check, integrity check, logical consistency check, outlier data check, time window
check, combined medication check, adverse event check, etc.
(3) Data archiving

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After completing data entry and verification as required, case report forms shall
be archived in numerical order with inclusion of retrieval catalogs for reference.
Electronic data files — including databases, inspection procedures, analytical
programs, results, coding manuals, and explanatory documents — should be
categorized and stored with multiple backups on different disks or storage media to
ensure proper preservation against damage. All original records must be retained for
the duration specified by relevant regulations.
8.2 Statistical analysis plan
The research data were processed using SPSS26.0 statistical software. In the
univariate analysis of collected data, continuous measurement data were presented
as mean ± standard deviation, categorical data as frequency, and measurements
with normal distribution were analyzed using t-tests. Categorical data were
statistically evaluated through Pearson's chi-square test or Fisher's exact test.
Significant covariates were controlled during grouping and adjusted in subsequent
analyses. All statistically significant risk factors underwent multivariate analysis
via logistic regression. Survival analysis utilized Kaplan-Meier method and
log-rank test. Statistical significance was defined as P values <0.05.
9. Technology Roadmap

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10. Data security plan
The researchers shall keep the results, protocols and other information of the
trial strictly confidential. All information such as the implementation, protocol,
design, results, data collection, CRF and informed consent form shall be kept
separately and confidentially, and no unauthorized investigator or other personnel
shall have access to them.
11. Risk/benefit assessment
11.1 Benefits (individual and societal)
Personal Benefits: [1] Cost Savings: The study will purchase relevant
insurance for patients, which saves them money. For patients with limited
financial means, clinical trials are the optimal choice. [2] Enhanced Care and
Monitoring: Clinical trials are typically conducted by leading experts in the field
and reputable hospitals. During enrollment, patients receive better care and
attention during hospitalization, examinations, treatments, and follow-ups. In
case of emergencies requiring urgent treatment, prompt medical intervention can

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be provided.
Social benefits: This study protocol has better efficacy and less toxic side effects
for high-risk locally advanced nasopharyngeal carcinoma, providing a new
treatment plan for high-risk locally advanced nasopharyngeal carcinoma
11.2 risk
This intervention study involves collecting clinical data from hospitalized
patients and conducting follow-up through outpatient visits, phone calls, or
WeChat. Throughout the study period, researchers will strictly adhere to the
protocol of "Trevirizumab + Induction Chemotherapy Sequential Radiotherapy
Combined
with
Omega-3
Therapy
for
Local
Advanced
Nasopharyngeal
Carcinoma: A Phase II, Single-Arm Clinical Study." Major treatment risks
include adverse reactions from tririzumab immunotherapy, albumin-bound
paclitaxel
chemotherapy,
cisplatin
chemotherapy,
radiotherapy,
and
oral
Omega-3 supplementation. The study will only commence after approval by the
ethics committee, with strict confidentiality required for patient privacy, raw
data, research outcomes, and protocols. All research materials must be stored
separately and exclusively, accessible only to authorized personnel. In cases of
severe adverse events (including death, life-threatening conditions, disability,
prolonged hospitalization, or deformities), researchers must complete the
"Severe Adverse Event Report Form" and submit reports to the Medical Device
Department and Safety Supervision Department of the National Medical
Products Administration, local drug regulatory authorities, study implementers,
and ethics committees within 72 hours, signing and noting the date. Emergency
situations involving particularly severe or fatal adverse events require immediate
communication via the fastest available means. Implementers must also
promptly notify relevant participating institutions while ensuring compliance
with all legal reporting procedures.
11.3 Protection of special groups
Research targeting vulnerable populations such as pregnant women must
carefully evaluate risks and benefits. While strictly adhering to China's relevant

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regulations, it is crucial to develop practical review and management protocols
that effectively protect participants' rights. Priority should not be given to
recruiting vulnerable groups simply because they are easier to enroll, as this
could expose them to research risks while benefiting other populations through
study outcomes. Informed consent remains the cornerstone of protecting special
populations,
particularly
vulnerable
groups.
Individuals
lacking
sufficient
cognitive capacity to give or withhold consent should not participate in such
studies without legal guardianship authorization. When recruiting vulnerable
populations, priority should be given to addressing their specific health issues,
with
special
protections
provided
throughout
the
research
process.
Comprehensive
safeguards
must
be
implemented
through
external
legal
frameworks, ethical oversight, and scientists' professional ethics to ensure the
rights of vulnerable groups are genuinely protected.
12. Ethical issues in research
12.1 Ethical approval
The study protocol, written informed consent forms, and all materials
directly related to participants must be submitted to the ethics committee for
review. The research may only commence after obtaining written approval from
the ethics committee. Investigators are required to submit annual reports to the
ethics committee at least once per year (if applicable). When suspending or
concluding a study, investigators must notify the ethics committee in writing. All
changes made during the study (such as revisions to the protocol and/or
informed consent forms) must be promptly reported to the ethics committee.
These modifications shall not be implemented without prior approval from the
ethics committee, except when they eliminate obvious and direct risks to
participants. In such cases, the ethics committee will be notified immediately.
12.2 Informed consent
Researchers must provide subjects or their guardians with an easily
understandable and ethics committee-approved informed consent form, and
allow sufficient time for them to consider the study. Subjects may not be

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enrolled until they have signed a written informed consent form. Throughout the
study, all updated versions of the consent form and written information will be
provided to participants. The consent form shall be retained as an important
clinical trial document for reference.
13. Annual plan
From June 01,2025 to September 30,2025: Collect relevant literature data,
determine baseline data and index data, and start recruitment.
From October 01,2025 to December 31,2028: Screen eligible nasopharyngeal
carcinoma cases, complete the enrollment of cases with the expected designed
sample size, observe patients, assess the condition, collect indicators and follow up
prognosis for the included cases according to the experimental steps designed by
each group, and register the data
From January 01,2029 to December 31,2029: collect and sort out test data,
conduct statistical analysis, write papers, improve papers and publish papers
14. Assessment indicators
(1) To train a master's student;
(2) Publish an SCI paper.
15. Preliminary research basis and working conditions
When selecting cases, the research team must strictly follow inclusion criteria
and exclude patients who do not meet them. Researchers must provide detailed
information to the patients and obtain informed consent. Approval from the ethics
committee and regulatory authorities is required to ensure that the study complies
with ethical and regulatory requirements and protects the rights of participants
16.Other issues that need to be explained
not have
16.1 Project cooperation
not have
16.2 Form of publication and authorship arrangement of the results
not have