Study Objectives
1. Primary Objective:
The core aim of this study is to investigate whether the sequential approach of Spatially Fractionated Radiotherapy followed by 3 cycles of induction chemotherapy combined with Iparomlimab and Tuvonralimab, definitive chemoradiotherapy, and maintenance therapy with the Iparomlimab and Tuvonralimab can improve the 2-year event-free survival (EFS) rate in patients with locoregionally advanced bulky head and neck squamous cell carcinoma (HNSCC). 2. Secondary Objectives:s
To analyze the impact of this integrated treatment regimen on key efficacy endpoints, including:
Objective response rate (ORR), Duration of response (DoR), Distant metastasis-free survival (DMFS), Local region recurrence-free survival (LRRFS), Overall survival (OS)。 2. Study Endpoints
(1) Primary Endpoint and Definition: 2-Year Event-Free Survival (EFS) Rate (2) Secondary Endpoints and Definitions:
1. 2-Year Overall Survival (OS) Rate 2. 2-Year Distant Metastasis-Free Survival (DMFS) Rate. 3. 2-Year Local Region Recurrence-Free Survival (LRRFS) Rate. 4. Objective Response Rate (ORR). 5. Duration of Response (DoR). 6. Quality of Life (QoL):
Assessed across multiple domains:
Physical Function: Measured via tools like the 6-minute walk test or ADL (Activities of Daily Living) scale.
Psychological Status: Evaluated using instruments such as HAMD (Hamilton Anxiety and Depression Scale) or MMSE (Mini-Mental State Examination).
Social Function: Assessed via social engagement questionnaires (e.g., HAQ-DI \[Health Assessment Questionnaire-Disability Index\]).
Spiritual Well-being: Evaluated using tools like PIL (Purpose in Life test). Clinically meaningful improvements in these domains before and after treatment define successful QoL endpoints (e.g., positive changes in physical, psychological, social, and spiritual health in cardiac patients). 7. Safety:
The nature and severity of adverse reactions associated with the treatment. 8. Tolerability:
The degree to which patients can endure treatment-related side effects.
Age between 18 and 75 years, both sexes eligible;
Histologically confirmed head and neck squamous cell carcinoma (HNSCC), diagnosed as locoregionally advanced disease with measurable primary tumor and/or cervical metastatic lymph nodes >5 cm in maximum diameter, and deemed unresectable by surgical evaluation;
Treatment-naive (no prior anti-tumor therapy);
At least one measurable lesion (excluding brain metastases) per RECIST 1.1 criteria;
Those with a history of severe immediate - type allergic reactions to any of the drugs used in this study；
Within six months before screening, having any of the following conditions: myocardial infarction, severe/unstable angina pectoris, coronary/peripheral artery bypass grafting, symptomatic congestive heart failure, cerebrovascular accident, transient ischemic attack, or symptomatic pulmonary embolism. Patients known to have coronary artery disease, congestive heart failure that doesn't meet the above criteria, or a left ventricular ejection fraction of less than 50% must have an optimally stable medical regimen as determined by the treating physician. If appropriate, a cardiologist can be consulted；
Individuals who have received anti - tumor vaccines or live vaccines within four weeks before the first administration of the study drug；
Those with well - controlled type 1 diabetes.
Second Affiliated Hospital of Nanchang University
Lead sponsor
Qilu Pharmaceutical Co., Ltd.
Collaborator