NCT07041788

Iparomlimab and Tuvonralimab Combined With SFRT and Definitive Chemoradiotherapy in Locoregionally Advanced Bulky HNSCC

A Prospective, Single-Arm Clinical Trial of Iparomlimab and Tuvonralimab Combined With Spatially Fractionated Radiotherapy and Definitive Chemoradiotherapy in Locoregionally Advanced Bulky Head and Neck Squamous Cell Carcinoma

• Status: Not Yet Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 25 (estimated)
• Sponsor: Second Affiliated Hospital of Nanchang University · Academic / Other
• Sex: All
• Age: 18 Years – 75 Years
• Healthy volunteers: Not accepted

Summary

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.

Detailed description

I. Study Design and Technical Route Details 1. Stratified Implementation of Treatment Protocols 1. Spatially Fractionated Radiotherapy (SFRT) Phase Technical Parameters: Three-dimensional conformal radiotherapy (3D-CRT) or intensity-modulated radiotherapy (IMRT) is used to deliver a single high-dose fraction to the primary tumor and bulky metastatic lymph nodes (≥5 cm), with a prescribed dose of 10-20Gy/1 fraction. Dose-volume histogram (DVH) optimization ensures target coverage while limiting doses to organs at risk (e.g., spinal cord ≤45Gy, parotid gland mean dose ≤26Gy). Timing: A positioning CT scan (slice thickness ≤3 mm) is completed within 7 days of enrollment. The radiation oncologist contours the target volumes, and the physicist designs the treatment plan, which is reviewed by a multidisciplinary team (MDT) before implementation. 2. Induction Chemotherapy Combined with Immunotherapy Phase Drug Regimen: Docetaxel: 75mg/m², intravenous drip, d1, Q3W for 3 cycles (body surface area calculated using measured height and weight, precise to 0.01m²). Cisplatin: 25mg/m², intravenous drip, d1-3, Q3W for 3 cycles (hydration pretreatment required, daily fluid intake ≥2000ml, electrolyte monitoring). Iparomlimab and Tuvonralimab: 5mg/kg, intravenous infusion, d1, Q3W for 3 cycles (diluted in 100ml 0.9% sodium chloride solution, infusion duration ≥30 minutes; electrocardiographic monitoring required for the first dose). Cycle Transition: Induction therapy starts within 7 days after SFRT. Each chemotherapy cycle requires confirmation of normal blood counts (ANC ≥1.5×10⁹/L, PLT ≥90×10⁹/L) and liver/kidney function (ALT/AST ≤2.5×ULN) before initiation. 3. Definitive Concurrent Chemoradiotherapy Phase Radiotherapy Protocol: Target Volume Definition: GTVₜₙ₀ (primary tumor) receives 70Gy/30-33 fractions, GTVₙ (positive lymph nodes) receives 66-70Gy/30-33 fractions, and clinical target volume (CTV) receives 54-60Gy/30-33 fractions. IMRT is used with daily fractions (2Gy/fraction), total treatment time ≤6 weeks. Concurrent Chemotherapy: Cisplatin 100mg/m², infused over 3 days (d1-3), Q3W for 2 cycles. Chemotherapy starts simultaneously with radiotherapy, within 48 hours of each other. 4. Immunotherapy Maintenance Phase Protocol: Iparomlimab and Tuvonralimab 5mg/kg, Q3W, intravenous infusion for 14 cycles (total treatment duration \~1 year). Discontinuation Criteria: Disease progression (RECIST 1.1), intolerable toxicity (CTCAE ≥3), patient withdrawal of informed consent, or investigator-determined need to exit. 2\. Technical Details of Efficacy Assessment Imaging Evaluation: Baseline Scans: Pre-enrollment head and neck contrast-enhanced CT/MRI (slice thickness ≤3 mm), chest CT, and whole-body bone scan; PET-CT as needed. Dynamic Evaluation: Repeat scans at the end of induction therapy, 1 month after concurrent chemoradiotherapy, and every 12 weeks during follow-up. Image registration techniques ensure target reproducibility. Biomarker Detection: Peripheral blood samples (5ml EDTA anticoagulated tubes) are collected before treatment, after induction therapy, and during maintenance therapy to detect PD-L1 expression (immunohistochemistry), T-cell subsets (flow cytometry), and 12 cytokines (ELISA, including IL-1β, IL-6, TNF-α, etc.). II. Safety Management System 1. Adverse Event (AE) Monitoring and Management Real-Time Tracking: AEs are recorded at each visit with details on onset time, duration, severity (CTCAE 5.0 grading), and causality to treatment. Particular attention is paid to immune-related adverse events (irAEs), such as pneumonitis, colitis, and thyroid dysfunction. Grading Management: Grade 1-2 AEs: Close observation with symptomatic support as needed (e.g., antiemetics, antipyretics); no dose adjustment required. Grade 3 AEs: Treatment suspension until recovery to ≤Grade 1; restart with unchanged Iparomlimab/Tuvonralimab dose, while chemotherapy dose may be reduced by 20%. Grade 4-5 AEs or Fatal irAEs: Permanent discontinuation; multidisciplinary consultation initiated, with potential administration of glucocorticoids (e.g., methylprednisolone 1-2mg/kg/d) or immunosuppressants. 2. Special Toxicity Monitoring Hematological Toxicity: Weekly blood count monitoring during induction and concurrent chemotherapy. For ≥Grade 3 neutropenia or thrombocytopenia, G-CSF (e.g., PEG-rhG-CSF 6mg subcutaneously) or platelet transfusions are administered, with prophylactic antibiotics (e.g., levofloxacin) until ANC ≥1.0×10⁹/L. Radiation-Induced Injury: Weekly assessment of oral mucositis (RTOG grading) and skin reactions (CTCAE) during radiotherapy. Patients receive oral rinses (e.g., chlorhexidine) and skin protectants (e.g., Biafine); severe cases require radiotherapy suspension and analgesia. III. Data Management and Quality Control 1. Data Collection and Documentation Case Report Form (CRF): An electronic CRF (eCRF) system is used for real-time recording of baseline characteristics, treatment processes, efficacy evaluations, and AE data to ensure traceability. Biological Sample Management: Tumor tissue samples (surgical or biopsy specimens) and blood samples are stored at -80°C with unique identifiers. A sample tracking database records storage locations, collection times, and usage (limited to study-related testing). 2. Quality Control Measures Internal Audits: Research coordinators verify CRF data integrity weekly, with quarterly on-site audits by the institutional office focusing on treatment compliance, AE underreporting, and sample management gaps. External Review: An independent Data Monitoring Committee (DMC) convenes annually to review safety data and efficacy endpoints. A predefined stopping rule triggers early termination if treatment-related mortality ≥2%. IV. Ethics and Compliance 1. Ethical Review Process Initial Approval: The study protocol, informed consent form (ICF), and 附属文件 (supporting documents) must undergo review and obtain approval from the Ethics Committee of the Second Affiliated Hospital of Nanchang University before initiation. Protocol Amendments: Any protocol modifications (e.g., dose adjustments, inclusion/exclusion criteria) require resubmission to the Ethics Committee for review, with amendments communicated to all research staff upon approval. 2. Protection of Subject Rights Informed Consent: Principal investigators provide detailed explanations of study objectives, risks, and benefits to subjects and their families, allowing a 48-hour consideration period. Informed consent is confirmed through written signatures and audio-video recording to ensure unambiguous understanding. Insurance Coverage: Each subject is enrolled in a clinical trial liability insurance (¥300,000 per subject), covering medical expenses and compensation for treatment-related injuries. V. Human Genetic Resources Management Sample Usage Scope: Samples are used exclusively for study-related biomarker testing and are not provided to external parties or exported. Destruction Procedures: Remaining samples are destroyed under dual supervision after study completion, with documentation of destruction time, quantity, and method, subject to Ethics Committee approval.

Conditions

• Cancer

Interventions

Type	Name	Description
DRUG	Iparomlimab and Tuvonralimab Injection	Induction 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.

Timeline

• Start date: 2025-07-10
• Primary completion: 2028-07-09
• Completion: 2030-07-09
• First posted: 2025-06-27
• Last updated: 2025-06-27

Locations

1 site across 1 country: China