A Study of TQB2450 in Combination With Intensity-modulated Radiotherapy in Patients With Inoperable Locally Recurrent Nasopharyngeal Carcinoma

Study Overview
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Brief Summary
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This is a study to evaluate the efficacy and safety of TQB2450 injection combination with Intensity-modulated Radiotherapy in patients with inoperable locally recurrent nasopharyngeal carcinoma.

Official Title
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An Open, Single-arm, Single-center, Phase II Clinical Trial of TQB2450 in Combination With Intensity-modulated Radiotherapy in Patients With Inoperable Locally Recurrent Nasopharyngeal Carcinoma

Conditions
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Nasopharyngeal Carcinoma

Intervention / Treatment
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* Drug: TQB2450
* Radiation: Intensity modulated radiotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 1. Understood and Signed an informed consent form; 2. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1; Life expectancy ≥ 3 months; 3. Local recurrence of non-keratinizing nasopharyngeal carcinoma diagnosed by histopathology and/or cytology; Clinical stage: rT2-4N0-3M0 , RII-IVa phase (AJCC eighth edition); 4. The recurrence time is more than 12 months from the end of the first course of radiotherapy, without other systemic or local anti-tumor treatment; 5. At least one measurable lesion (based on RECIST 1.1); 6. Adequate laboratory indicators; 7. No pregnant or breastfeeding women, and a negative pregnancy test. Exclusion Criteria: 1. Operable patients with local recurrence, including rT2 (the tumor is confined to the surface of the parapharyngeal space, and the distance from the internal carotid artery > 0.5 cm) and rT3 (the tumor is confined to the bottom wall of the sphenoid sinus, and the distance from the internal carotid artery and cavernous sinus > 0.5 cm) ; 2.Combined diseases and medical history: Accompanied by nasopharyngeal necrosis, radiation brain injury, severe neck fibrosis, or other ≥grade 3 radiation complications, the investigator has assessed that the risk is extremely high and not suitable for radiotherapy; Has other malignant tumors within 3 years; Unalleviated toxicity ≥ grade 1 due to any previous anticancer therapy; Has received major surgical treatment, open biopsy, or obvious traumatic injury within 28 days before the first administration; Long-term unhealed wounds or fractures; Arterial/venous thrombosis events occurred within 6 months, such as cerebrovascular accidents (including temporary ischemic attacks, cerebral; hemorrhage, cerebral infarction), deep vein thrombosis and pulmonary embolism; Has drug abuse history that unable to abstain from or mental disorders; Has any severe and/or uncontrollable disease. 3.Tumor-related symptoms and treatment: Diagnosed local recurrence and received surgery, chemotherapy, radiotherapy or other anti-cancer therapies before first administration; Has received NMPA approved Chinese patent medicines with anti-tumor indications; Has received relevant immunotherapy drugs for PD-1, PD-L1, CTLA-4, etc.; Uncontrollable pleural effusion, pericardial effusion or ascites that still needs to be drained repeatedly (as judged by the investigator); 4.Research and treatment related: Has vaccinated with vaccines or attenuated vaccines within 4 weeks prior to first administration; Have severe hypersensitivity after using monoclonal antibodies; Active autoimmune diseases that require systemic treatment (such as the use of disease-relieving drugs, corticosteroids, or immunosuppressive agents) occurred within 2 years before the start of the study treatment; Has immunodeficiency or received systemic glucocorticoid therapy or any other form of immunosuppressive therapy, and continue to use within 2 weeks of the first administration; 5.Has participated in other anti-tumor drug clinical trials within 4 weeks before the study; 6.According to the judgement of the investigators, there are other factors that may lead to the termination of the study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TQB2450+Intensity modulated radiotherapy<br>TQB2450 1200 mg administered intravenously (IV) on Day 1 of each 21-day；The total dose of radiotherapy should meet PTVnx: 60Gy/27Fr/2.22Gy, PTVnd: 60-64Gy/27Fr/2.22-2.37Gy, PTV1: 54Gy/27Fr/2.00Gy, once a day, 5 times/week. | Drug: TQB2450<br>* TQB2450 is a humanized monoclonal antibody targeting programmed death ligand-1 (PD-L1), which prevents PD-L1 from binding to PD-1 and B7.1 receptors on T cell surface, restores T cell activity, thus enhancing immune response and has potential to treat various types of tumors.<br>Radiation: Intensity modulated radiotherapy<br>* Intensity-modulated conformal radiotherapy (IMRT) is a kind of three dimensional conformal radiotherapy, which requires the dose intensity in the radiation field to be adjusted according to certain requirements.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall response rate (ORR) | Percentage of participants achieving complete response (CR) and partial response (PR). | up to 48 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease control rate（DCR） | Percentage of participants achieving complete response (CR) and partial response (PR) and stable disease (SD). | up to 48 weeks | 
| Duration of Response (DOR) | The time when the participants first achieved complete or partial remission to disease progression. | up to 48 weeks | 
| Progression-free survival (PFS) | PFS defined as the time from first dose until the first documented progressive disease (PD) or death from any cause. | up to 48 weeks | 
| 12-month progression-free survival rate | 12-month PFS defined as the time from first administration until the first documented progressive disease (PD) or death from any cause within 12 months. | up to 48 weeks | 
| 12-month survival rate | 12-month survival rate defined as the time from first administration to death from any cause within 12 months. | up to 48 weeks | 
| 24-month survival rate | 24-month survival rate defined as the time from first administration to death from any cause within 24 months. | up to 96 weeks | 
| Local regional recurrence-free survival (LRRFs) | The time interval between the patient's first medication and the appearance of local imaging progress. | up to 48 weeks | 
| Distant metastasis-free survival (DMFS) | The time interval between the patient's first medication and the appearance of distant metastasis imaging progression or death. | up to 48 weeks | 
| Overall survival (OS) | OS defined as the time from randomization to death from any cause. Participants who do not die at the end of the extended follow-up period, or were lost to follow-up during the study, were censored at the last date they were known to be alive. | up to 96 weeks |