To Evaluate the Efficacy and Safety of Accelerator-Based Boron Neutron Capture Therapy (AB-BNCT) Combined With NBB-001 and NBB-002 for Patients With Recurrent Head and Neck Malignancies

A Single-Arm, Open-Label Phase II Clinical Trial to Evaluate the Efficacy and Safety of Accelerator-Based Boron Neutron Capture Therapy (AB-BNCT) Combined With NBB-001 and NBB-002 for Patients With Recurrent Head and Neck Malignancies

This Phase II study, titled 'A Single-Arm, Open-Label Phase II Clinical Trial to Evaluate the Efficacy and Safety of Accelerator-Based Boron Neutron Capture Therapy (AB-BNCT) Combined with NBB-001 and NBB-002 for Patients with Recurrent Head and Neck Malignancies.', aims to assess the efficacy and safety of BNCT in patients with Recurrent Head and Neck Malignancies.

Primary Objective: To evaluate the efficacy of Boron Neutron Capture Therapy (BNCT) in patients with recurrent head and neck malignancies.Secondary Objectives:To evaluate the efficacy of BNCT in patients with recurrent head and neck malignancies based on secondary efficacy endpoints;To characterize the pharmacokinetic (PK) profiles and radiation dosimetric characteristics of NBB-002 in patients with recurrent head and neck malignancies;To evaluate the safety of BNCT in patients with recurrent head and neck malignancies;To evaluate the equipment performance and equipment deficiencies of the boron neutron capture therapy system.

Inclusion Criteria:

1. Subjects must give informed consent to this study before the trial and voluntarily sign a written informed consent form;
2. Age>=18 years old and <=75 years old, gender is not limited;
3. Histologically or cytologically confirmed head and neck malignancies.
4. Patients have head and neck malignancies with local recurrence or regional lymph node recurrence, with prior failure of or intolerance to local therapy plus at least one line of systemic therapy, or no available standard treatment options.
5. Multiple target lesions need to be covered in a single treatmentMultiple target lesions need to be covered in a single treatment
6. At least 1 measurable tumor lesion according to RECIST v1.1 criteria; 7.18F-BPA PET/CT scan demonstrated that the boron concentration ratio (TNR) of tumor and normal tissue should be ≥2.5

8.Adequate hematologic function, liver function and renal function: 9.Expected survival >=3 months; 10.Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2; 11.For patients with prior radiotherapy, the total cumulative dose to target lesions can not exceed 75 Gy.

12.The adverse reactions of previous anti-tumor therapy must resolve to Grade ≤1 according to NCI CTCAE Version 6.0.

13.Female and male patients of reproductive potential must agree to utilize medically accepted effective contraception from initiation of informed consent until 6 months following BNCT treatment.

Exclusion Criteria:

1. Subjects with known hypersensitivity to any active ingredient or excipient of the investigational product, severe fructose intolerance, or a history of other severe allergic reactions who are judged by the investigator to be unsuitable for participation in this trial.
2. Subjects with active multiple primary malignancies.
3. Subjects with multiple distant metastases.
4. There is a risk of arterial hemorrhage associated with tumor involvement, and there is no effective preventive measure
5. Subjects who received radiotherapy to target lesions within 3 months prior to administration of NBB-001.
6. Subjects who have received prior particle implantation therapy.
7. Subjects receiving any systemic anti-tumor therapy (including systemic chemotherapy, immunotherapy, targeted therapy, etc.) within 4 weeks or 5 half-lives prior to NBB-001 administration; or subjects receiving anti-tumor Chinese herbal medicines or proprietary Chinese medicines within 2 weeks before BNCT treatment.
8. Subjects who have received major surgery involving vital organs (excluding needle biopsy) or experienced significant trauma within 4 weeks prior to NBB-001 administration.
9. Subjects receiving any investigational medicinal product or investigational devices within 4 weeks prior to NBB-002 administration
10. Subjects who have experienced a serious arterial/venous thromboembolic event within 6 months prior to administration of NBB-002 or have a prior history of stroke; subjects with decompensated congestive heart failure (New York Heart Association [NYHA] Class III or IV), or severe cardiovascular disease confirmed by echocardiography and 12-lead electrocardiogram, who are judged by the investigator to be ineligible for participation in this trial.
11. Subjects with clinically significant active COPD or other severe chronic respiratory diseases, or active infection with clinical manifestations or organ dysfunction, who are deemed ineligible for this trial by the investigator
12. Subjects with evidence of other serious or uncontrolled systemic diseases deemed by the investigator.
13. Subjects diagnosed with phenylketonuria (PKU).
14. Subjects with any of the following: a) A cardiac pacemaker; b) Non-removable metallic implants within the single treatment area assessed by the investigator to preclude treatment; or non-removable metallic implants outside the single treatment area that cannot be effectively shielded and are assessed by the investigator to preclude treatment.
15. Known history of drug or alcohol dependence.
16. Subjects with a history of immunodeficiency, including positive HIV antibody testing.
17. Subjects with other conditions deemed by the investigator to potentially affect compliance or render them unsuitable for participation in this trial, such as diseases that may impair the ability to adhere to trial requirements or compromise capacity to provide informed consent.