CELL INTELLIGENCE · 肿瘤细胞治疗研究

Inclusion Criteria:

1. Male or female adults aged 19 years to less than 70 years who have received sufficient explanation regarding the purpose, methods, potential benefits, and risks of the study and have voluntarily provided written informed consent.
2. Histologically confirmed IDH-wildtype glioblastoma (GBM), WHO Grade 4, according to the WHO CNS5 2021 classification.
3. Completion of standard first-line treatment (surgery + radiotherapy + concurrent TMZ → 6 cycles of adjuvant TMZ).
4. Confirmed first recurrence, defined by at least one of the following:

(1) Progressive Disease according to RANO 2.0 criteria on MRI more than 12 weeks after completion of radiotherapy.

(2) If within 12 weeks after completion of radiotherapy, pseudoprogression has been excluded through the RANO 2.0 confirmation procedure (confirmatory scan), and persistent progression has been confirmed on two consecutive scans at least 4 weeks apart.

5\. No antitumor treatment, including chemotherapy, immunotherapy, targeted therapy, or radiotherapy, after confirmation of recurrence, except surgery.

6\. KPS ≥ 60.

7\. Adequate organ function permitting study treatment and surgery, including:

1. Absolute neutrophil count (ANC) ≥ 1.5 × 10\^9/L.
2. Platelets ≥ 100 × 10\^9/L.
3. Hemoglobin (Hb) ≥ 9.0 g/dL.
4. AST and ALT ≤ 2.5 × ULN.
5. Total bilirubin ≤ 1.5 × ULN.
6. Serum creatinine ≤ 1.5 × ULN or eGFR ≥ 50 mL/min/1.73 m\^2.

8\. Adequate peripheral venous access for leukapheresis or ability to undergo central venous catheter placement.

9\. Life expectancy of at least 12 weeks, as determined by the investigator.

10\. Female participants who are postmenopausal, defined as 12 months of amenorrhea without a medical cause, or women of childbearing potential with a negative pregnancy test.

11\. Women of childbearing potential and male participants who agree to use appropriate contraception (e.g., condoms, hormonal contraceptives, oral contraceptives, intrauterine devices, or sterilization) during the study and for 3 months after the last administration of the study treatment.

Exclusion Criteria:

1. Two or more recurrences or prior antitumor treatment for a previous recurrence.
2. Confirmed leptomeningeal dissemination or extracranial metastasis.
3. Requirement for chronic high-dose systemic corticosteroids (e.g., \>10 mg/day prednisolone equivalent) or continuous use of other immunosuppressive drugs. Low-dose corticosteroid use at enrollment is permitted; however, the washout criteria must be met at each study treatment administration.
4. Active autoimmune disease requiring systemic immunosuppressive treatment within the past 2 years (e.g., steroids ≥10 mg/day prednisolone equivalent or immunosuppressive agents). Exceptions include adequately treated Basedow/Graves disease or Hashimoto thyroiditis with stable thyroid hormone replacement therapy, vitiligo, resolved childhood asthma, type 1 diabetes, and localized skin disorders.
5. A positive result for any of the following infectious disease tests performed at screening. However, participants with a positive result may participate if the investigator determines that it has no clinically significant impact on participation in the study:

(1) HBsAg/HBV NAT. (2) HCV Ab/HCV NAT. (3) HIV Ab/HIV NAT. (4) Syphilis (non-treponemal/treponemal). (5) HTLV Ab. (6) CMV Ab/CMV NAT.

6\. Uncontrolled active infection or any other infectious disease considered by the investigator to be inappropriate for participation in the study.

7\. History of another malignancy within the past 3 years, except adequately treated basal cell or squamous cell carcinoma of the skin or cervical carcinoma in situ.

8\. Contraindication to leukapheresis (e.g., severe cardiovascular disease or coagulation disorder).

9\. Serious medical or psychiatric condition that may affect participation in the study.

10\. History of a severe allergic reaction or other serious hypersensitivity to the study treatment or any of its excipients.

11\. Pregnant or breastfeeding women.

12\. Participants planning pregnancy during the study.

13\. Participants considered by the investigator unlikely to comply with study treatment, study procedures, or follow-up.

14\. Any other participant considered by the investigator to be unsuitable for participation in the study.

主要终点：Progression-Free Survival (PFS) · Progression-free survival (PFS) is defined as the time from the first administration of CHANK-101 to the first occurrence of disease progression according to RANO 2.0 criteria or death from any cause, whichever occurs first. · From the first administration of CHANK-101 until disease progression or death from any cause, whichever occurs first, assessed up to Week 48.
次要终点：Number of Participants With Adverse Events as Assessed by NCI-CTCAE Version 5.0；Progression-Free Survival at 6 Months (PFS-6)；Overall Survival (OS)

• CHANK-101 Treatment Group · EXPERIMENTAL · Participants will receive CHANK-101, an autologous natural killer (NK) cell therapy, by intravenous administration. The first administration will begin 4 to 6 weeks after leukapheresis, or 4 to 6 weeks after surgery for participants undergoing surgical resection of the recurrent lesion. CHANK-101 will subsequently be administered every 2 weeks for up to 12 administrations.

This multicenter, open-label, externally controlled clinical study is designed to evaluate the safety and efficacy of CHANK-101, an autologous natural killer (NK) cell therapy, in patients with recurrent glioblastoma. The primary objective is to evaluate progression-free survival (PFS) following CHANK-101 administration. Secondary objectives include evaluating safety and tolerability, progression-free survival at 6 months (PFS-6), and overall survival (OS).