A Phase 2 Study of HX301 in Patients with High-grade Giloma

Inclusion Criteria:

1. Signed informed consent form;

2. Age ≥ 18 years;

3. Expected survival ≥ 12 weeks;

4. Part I:1) Histologically confirmed high-grade glioma (WHO classification grade IIIor IV); 2) At least one prior temozolomide treatment; 3) Patients with recurrent orprogressive clinically assessed disease according to RANO criteria with evaluablelesions; Part II: Patients with histological or cytological diagnosis ofglioblastoma according to World Health Organization (WHO) classification (2021) whoreceived surgical treatment for the first time and standard concurrentchemoradiotherapy and who have not received any other prior treatment;

5. Part II: Subjects must undergo partial or complete surgical resection, and availableresults of postoperative brain contrast-enhanced MRI were documented as follows: 1)complete resection without gadolinium enhancement ; or 2) complete resection (80% ormore);

6. Part II: Subjects must complete initial radiotherapy combined with TMZ (concurrentchemoradiotherapy) for glioblastoma according to the Stupp regimen (Stupp 2005) (total radiation dose 5 4-60 G y);

7. Part I: If radiotherapy has been performed, the completion of radiotherapy shalllast for 3 months, or there shall be tumor progression or histopathologicalconfirmation of progression in the original radiation field within 3 months; PartII: there shall be no evidence of disease progression after chemoradiotherapy,except for pseudo progression;

8. Dexamethasone was administered at ≤ 5 mg/day at study entry.Corticosteroids shouldbe reduced as far as possible to the smallest dose necessary to control neurologicalsymptoms before receiving study treatment;

9. Karnofsky performance status (KPS) ≥ 70 within 1 4days prior to receiving studytreatment ;

10. Willing and able to comply with the protocol.

Exclusion Criteria:

1. Part II: Patients with recurrent glioblastoma;

2. Distant metastasis involving brainstem and meninges or extension of lesions tospinal cord;

3. Human immunodeficiency virus (HIV) antibody positive, syphilis antibody (Anti-TP)positive, hepatitis C virus (HCV) antibody positive and HCV RNA positive, hepatitisB virus surface antigen (HBsAg) positive and HBV DNA positive (HBsAg positiverequires further detection of HBV DNA, HBV DNA ≥ 200 IU/ml, or ≥ 10 3 copies/ml);

4. Hypersensitivity to temozolomide and/or components of HX301;

5. At risk for torsades de pointes (TdP): patients with a marked prolongation of theQT/QTc interval calculated using the Fredericia QT correction formula at baseline (eg, repeated demonstration of QTc interval > 470 ms), or a history of other TdPrisk factors (eg, heart failure, hypokalemia, family history of long QT syndrome),or patients who are currently taking medications that prolong the QT/QTc interval;

6. Grade ≥ 2 diarrhea at baseline;

7. Participation in another study involving an investigational drug within 30 daysprior to the first dose of study drug;