TTAC-0001 Phase II Trial With Recurrent Glioblastoma Progressed on Bevacizumab

Inclusion Criteria:

   1. Provision of signed and dated informed consent prior to any study specific procedures,
   sampling or analyses.

   2. Aged at least 18 years old

   3. Patients must have a histologically proven diagnosis of glioblastoma/gliosarcoma

   4. Patients must have previous treatment including bevacizumab

   5. Patients must have a radiological diagnosis of recurrent/relapsed or progressive
   glioblastoma/gliosarcoma after bevacizumab including therapy according to response
   assessment in neuro-oncology (RANO) criteria

   6. At least one confirmed measurable lesion or non measurable lesion as determined by
   RANO criteria

   7. Patients must undergo IDH1 mutational testing on a tumor specimen before entering the
   study. Immunohistochemistry (IHC) is sufficient for enrollment, although DNA
   sequencing may also be performed as per local institutional guidelines. Patients are
   eligible regardless of their tumor status.

   8. Karnofsky Performance Status (KPS) ≥ 70

   9. A person who satisfies the following criteria in hematologic, renal, and hepatic
   function tests (1) Hematologic tests - Absolute neutrophil count (ANC) ≥ 1.5 x 109/L -
   Platelets ≥ 75 x 109/L

   - Hemoglobin ≥ 9.0 g/dL (2) Blood coagulation tests

   - Prothrombin time (PT) ≤ 1.5 x Upper limit of normal (ULN)

   - Activated partial thromboplastin Time (aPTT) ≤ 1.5 x ULN (3) Hepatic function tests

      - Total bilirubin ≤ 1.5 x ULN

      - Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≤ 3 x ULN (4)
      Renal function test

      - Creatinine clearance (CrCl) ≥ 30 mL/minute calculated by Cockcroft-Gault formula

10. Life expectancy of at least 12 weeks

11. Females of child bearing potential must have a negative pregnancy test during
   screening and must not be breastfeeding or intending to become pregnant during the
   study.

12. Male patients with female partners of child-bearing potential must be willing to use
   two forms of acceptable contraception, including one barrier method, during their
   participation in this study and for 16 weeks following the last dose of the study.
   Refer to section 10.5.1 Restrictions, permitted methods of contraception and
   definitions.

Exclusion Criteria:

   1. Diagnosed with malignant tumors, except basal cell carcinoma, cutaneous squamous cell
   carcinoma, and noninvasive uterine cervical cancer treated within 2 years prior to
   receiving the first dose of treatment.

   2. The following concomitant diseases:

(1) Uncontrolled hypertension (systolic blood pressure [SBP] > 150 or diastolic blood
pressure [DBP] > 90 mmHg) (2) Uncontrolled seizures (3) Class III or IV heart failure
according to New York Heart Association (NYHA) classification (4) Oxygen-dependent chronic
disease (5) Active psychiatric disorder (schizophrenia, major depressive disorder, bipolar
disorder etc.). Treated depression with ongoing antidepressant medication is not an
exclusion.

3) Not recovered from AEs < National Cancer Institute -Common Terminology Criteria for
Adverse Events (NCI-CTCAE) grade 2 caused by CCRT 4) Treatment with bevacizumab including
therapy 2 weeks prior to receiving the first dose of treatment.

5) Undergone major surgery requiring general anesthesia or a respiratory assistance device
within 4 weeks prior to the baseline visit (within 2 weeks for video-assisted thoracoscopic
surgery [VATS] or open-and-closed [ONC] surgery) 6) Treated with other investigational
products within 4 weeks prior to the patient receiving the first dose of treatment.

7) A known history of severe drug hypersensitivity or hypersensitivity to a therapy similar
to the study drug 8) Unable to participate in the trial according to the investigator's
decision. 9) Patient not eligible for sequential MRI evaluations are not eligible for this
study 10) Previous therapy with VEGF-targeted agents except bevacizumab. 11) Known active
hepatitis B or hepatitis C infection 12) Has received a live vaccine within 30 days prior
to enrollment. Seasonal flu vaccines that do not contain live virus are permitted.

13) Has had a serious or non-healing wound, ulcer, or bone fracture within 28 days prior to
enrollment