A Phase 1/2 Dose Escalation and Expansion Study of Sonodynamic Therapy With SONALA-001 in Combination With Exablate 4000 Type 2.0 MR-Guided Focused Ultrasound in Subjects With Progressive or Recurrent Glioblastoma Multiforme (rGBM)

To determine Maximum Administered Dose (MAD), Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D) after a single treatment of MR-guided Focused Ultrasound (MRgFUS) energy in combination with SONALA-001 SDT (Phase 1)

时间窗: Up to 3 weeks post treatment

Determination of Recommended Phase 2 Dose of SONALA-001 SDT in combination with MRgFUS

Safety and Tolerability of SONALA-001 SDT as assessed by the frequency and severity of dose-limiting toxicities (DLTs)

时间窗: Day 1 to Day 21 post treatment

Safety and tolerability of SONALA-001 SDT Definitions of Dose Limiting Toxicities (DLTs): The DLT window is the 21-day period following the first study treatment per patient. DLTs are defined as the following events during the DLT window, not clearly related to underlying disease, disease progression or intercurrent illness, as determined by safety review committee: Any death Non-hematologic toxicity: Any CTCAE Grade 3 or higher Hy's law cases Moderate heating/burning at the scalp Grade 3 or greater neurological toxicities Evidence of clinically significant tissue damage outside the region targeted by MRgFUS Grade 3 or greater photosensitivity in subjects strictly following restrictions to light exposure to sunlight or room lights for 48 hours after SONALA-001 administration Hematologic toxicity: Grade 4 neutropenia for more than 7 days Grade 3 or higher thrombocytopenia with clinically significant bleeding Neutropenic fever

Safety and Tolerability of SONALA-001 SDT as assessed by the number of subjects with Adverse Events (AEs), adverse device effects (ADEs), serious AEs (SAEs) and serious device effects (SADEs)

时间窗: Day 1 to 12 months

Safety and tolerability of SONALA-001 SDT Definition of Adverse Event (AE) An AE is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after the first dose of investigational drug. Abnormal laboratory values or test results occurring after the first dose of investigational drug constitute AEs only if they induce clinical signs or symptoms, are considered clinically significant, require therapy (e.g., hematologic abnormality that requires transfusion or hematological stem cell support) except electrolytes which require replacement therapy and correct to CTCAE grade ≤ 1 within 48 hours unless considered life-threatening, or require changes in study medication(s).

Safety and Tolerability of SONALA-001 SDT as assessed by the number of subjects with abnormal hematology, chemistry, coagulation and urinalysis laboratory tests.

时间窗: Day 1 to 12 months

Lab tests covered by CTCAE version 5.0 or most current will be graded accordingly. For lab tests covered by CTCAE, a Grade 0 will be assigned for all non-missing values not graded as 1 or higher. Grade 5 will not be used. For lab tests where grades are not defined by CTCAE, results will be categorized by low/normal/high classifications based on lab normal ranges or categorized by normal/abnormal for character (descriptive) lab values.

Progression-free survival rate at 6 Months (Phase 2)

时间窗: 6 Months

To evaluate preliminary efficacy (PFS rate at 6 months) of the RP2D of ALA SDT treatments by mRANO in subjects with recurrent GBM

Safety of the RP2D of ALA SDT as assessed by the number of subjects with AEs/ADEs, SAEs/SADEs, abnormal laboratory tests, neurologic and physical examinations, vital signs, and ECGs.

时间窗: Day 1 to 12 months

Safety of the RP2D of ALA SDT