Adebrelimab Plus Temozolomide ± Hyperbaric Oxygen for Primary Glioblastoma

A Prospective, Randomized, Open-Label, Multicenter Phase II Study of Adebrelimab Combined With Temozolomide With or Without Hyperbaric Oxygen Therapy for Newly-Diagnosed Primary Glioblastoma

This is a prospective, randomized, open-label, multicenter phase II study. Newly-diagnosed primary glioblastoma patients who have undergone maximal safe resection or biopsy and completed standard concurrent chemoradiotherapy will be enrolled. Subjects will be randomized 1:1 into Arm A (Adebrelimab + Temozolomide + Hyperbaric Oxygen Therapy) or Arm B (Adebrelimab + Temozolomide). The primary endpoint is progression-free survival(PFS). Secondary endpoints include overall survival(OS), objective response rate(ORR), disease control rate(DCR), change of KPS score, safety including TRAE, irAE and SAE. Exploratory objectives include correlation analysis between baseline clinical characteristics / hyperbaric-oxygen-related biomarkers and efficacy-safety outcomes.

Inclusion Criteria:

• Age 18-70 years, male or female.
• Newly-diagnosed primary glioblastoma histologically-confirmed; received maximal safe resection or biopsy, and completed standard concurrent chemoradiotherapy with temozolomide.
• Dexamethasone dose ≤4 mg/day at initiation of adjuvant study treatment.
• Karnofsky Performance Status(KPS) ≥70.
• Expected survival ≥3 months.
• Adequate bone marrow: ANC ≥1.5×10^9/L; Hb ≥90 g/dL; PLT ≥100×10^9/L; WBC ≥3.0×10^9/L.
• Adequate liver function: ALT/AST/ALP ≤2.5×ULN (≤5×ULN if liver metastasis); total bilirubin <1.5×ULN.
• Adequate coagulation function: PT, APTT, INR ≤1.5×ULN.
• Female not pregnant / lactating; effective contraception required for fertile females and males during study and 6-month after last study treatment.
• Signed written informed consent, willing to comply with study procedures.
• Not participating in other interventional clinical trials.

Exclusion Criteria:

• Prior anti-angiogenic, targeted, immunotherapy (anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, CTLA-4 antibody etc.).
• Progressive disease according to iRANO criteria. Suspicious pseudo-progression should be further evaluated by advanced imaging.
• Multifocal glioblastoma (separate tumor lesions without overlapping T2/FLAIR signal), or leptomeningeal metastasis.
• Prior interstitial brachytherapy, implanted chemotherapy, local injection, convection-enhanced delivery; prior Gliadel wafer placement; prior Optune device usage.
• Tumor completely located in infratentorial region.
• Known hypersensitivity to temozolomide or adebrelimab components.
• Dexamethasone >4 mg/day at adjuvant treatment initiation.
• History of immunodeficiency, or receiving immunosuppressive agents within 7 days before first study drug (except dexamethasone ≤4 mg daily).
• Uncontrolled concurrent severe disease: active infection, symptomatic congestive heart failure, unstable angina, arrhythmia, uncontrolled hypertension or psychiatric condition interfering with study compliance.
• Active systemic autoimmune disease requiring systemic therapy within past 2 years; physiological replacement therapy (thyroxine, insulin etc.) are allowed.
• Medical conditions unsuitable for hyperbaric oxygen therapy or immunotherapy.
• Severe anemia or concomitant medications interfering temozolomide absorption.
• Uncontrolled major psychiatric disorder including depression with CESD-R score ≥16.
• Cognitive impairment preventing neuro-oncology assessment.
• Pregnant or lactating women.
• Participated in other relevant clinical trials within prior 3 months.
• Life-threatening complication or vegetative state after chemoradiotherapy.
• Other malignant tumor within past 5 years (except cured carcinoma in-situ, basal-cell skin carcinoma). Poor compliance unable to follow protocol.
• Substance-use disorder (DSM-V criteria: alcohol or drug addiction).
• Active cardiac disease within 6 months prior to screening: myocardial infarction, unstable angina; LVEF<50%, poorly controlled arrhythmia.
• Active infection or unexplained fever>38.5℃ at screening / before first dosing (fever attributed to tumor is permitted).
• Immunodeficiency including active hepatitis; HBV-DNA ≥1000 IU/ml; HCV-RNA ≥1000 IU/ml. Chronic HBV carrier with HBV-DNA<2000 IU/ml must receive concurrent antiviral treatment to be eligible.
• Investigator's judgment that subject is inappropriate for this trial.