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.
Single group
Iparomlimab and Tuvonralimab Injection
DrugInduction Therapy: Spatially Fractionated Radiotherapy: Administer 10-20 Gy in a single fraction to the tumor. Chemotherapy + Immunotherapy: Docetaxel 75 mg/m² IV on Day 1. Cisplatin 25 mg/m² IV on Days 1-3. Iparomlimab and Tuvonralimab Injection 5 mg/kg IV on Day 1. Cycles: Every 3 weeks (Q3W) for 3 cycles. Maintenance Therapy: Begin 4-6 weeks after radiotherapy completion. Iparomlimab and Tuvonralimab: Dose: 5 mg/kg diluted in 100 mL 0.9% NaCl or 5% glucose. Administration: IV infusion over ≥20 minutes (total duration including flushing ≤60 minutes). Cycles: Q3W for 14 cycles (maximum 1 year). Iparomlimab and Tuvonralimab Injection: Continue until disease progression, intolerable toxicity, initiation of new anti-tumor therapy, withdrawal of consent, or investigator decision to discontinue. Maximum treatment duration: 1 year.
2-year EFS (Event - Free Survival)
Event-Free Survival (EFS) rate: Defined as the time from enrollment to the occurrence of the first event among any of the following: disease progression (including local progression and distant metastasis), recurrence (i.e., reappearance of the tumor after treatment in cancer patients), death from any cause, etc. In other words, it represents the survival duration during the observation period when patients do not experience these predefined "events".
2 - year Overall Survival (OS) rate
2 - year Overall Survival (OS) rate: It refers to the proportion of patients who have not died from any cause within the two - year time frame starting from the enrollment. In various cancer clinical trials, regardless of whether the patient's death is caused by cancer itself or other comorbidities (such as infections, failure of other organs, etc.), the time from enrollment to death is defined as OS.
2 - year Distant Metastasis - Free Survival (DMFS) rate
2 - year Distant Metastasis - Free Survival (DMFS) rate: It refers to the proportion of patients whose disease has not developed distant metastasis within the two - year time frame starting from the enrollment. For example, in a clinical study of colorectal cancer, the focus is on the probability of patients surviving without distant organ metastases such as those in the liver and lungs.
2 - year Local Region Recurrence - Free Survival (LRRFS) rate
2 - year Local Region Recurrence - Free Survival (LRRFS) rate: It refers to the proportion of patients who experience no recurrence in the primary tumor site and its surrounding local regions within the two - year time frame starting from enrollment. For instance, in head and neck tumors, the survival probability of patients without tumor recurrence in the primary tumor site of the head and neck, adjacent lymph nodes, and other local regions after treatment represents LRRFS.
Overall Response Rate (ORR)
Overall Response Rate (ORR): Refers to the proportion of patients whose tumor volume reduction meets predetermined criteria and is maintained for a minimum duration. It typically includes cases of complete response (CR, defined as disappearance of all target lesions) and partial response (PR, defined as a ≥30% reduction in the sum of the longest diameters of target lesions), in accordance with RECIST V1.1 criteria.
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Second Affiliated Hospital of Nanchang University
Lead sponsor
Qilu Pharmaceutical Co., Ltd.
Collaborator
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