Proof-of-Concept Study of ACT001 in Adult Patients With Recurrent Glioblastoma Harbouring STAT3-High Signature

Inclusion criteria

• Histologically confirmed diagnosis of GBM according to 2021 WHO classification
• Availability of tumor tissue representative of GBM from definitive surgery or biopsy and tested to harbour STAT3-High Signature
• Previous treatment with at least radiation therapy
• Documented recurrence of malignant glioma by diagnostic biopsy, resection or MRI performed within 21 days of study enrolment per RANO criteria.

There is no limit on number of previous recurrences or lines of treatment

• At least 12 weeks after the end of prior radiation therapy is required unless there is either: i) histopathologic confirmation of recurrent tumor, or ii) n new enhancement on MRI outside of the radiation treatment field
• An interval of at least 4 weeks after the last administration of any investigational agent or any other treatment prior to first dose of STAT3 inhibitor
• Age 21 years or older on the day of signing informed consent
• Karnofsky performance status (KPS) of 70 or higher
• Patient has adequate bone marrow, renal, and hepatic function ≤ 21 days prior to study enrolment (Step 2) as follows:

• Absolute neutrophil count (ANC) ≥1,500/mm3
• Platelets ≥ 100,000/mm3
• Hemoglobin (Hgb) ≥ 9.0 g/dL (Note: The use of transfusion or other intervention to achieve Hgb ≥ 9.0 g/dL is acceptable.)
• Renal function: calculated creatinine clearance ≥ 30 mL/min by the Cockcroft-Gault formula
• Hepatic function: Total bilirubin, Aspartate Aminotransferase (AST), and Alanine Aminotransferase (ALT) ≤ 1.5 times upper limit of normal (ULN). Patients with Gilbert's syndrome documented in medical history may be enrolled if bilirubin is < 3 times ULN.

Exclusion criteria

• Presence of extracranial metastatic or leptomeningeal disease
• Previous or current treatment with a JAK or STAT3 inhibitor
• Previous or current treatment with bevacizumab/VEGF inhibitor
• Patient is a lactating or pregnant female.
• Symptomatic intra-tumoural haemorrhage
• Severe, active co-morbidity, defined as follows:

• Patients with clinically defined Acquired Immune-Deficiency Syndrome (AIDS)-defining illness.
• Active connective tissue disorders, such as lupus or scleroderma, that in the opinion of the Investigator may put the patient at high risk of toxicity
• Any other major medical illnesses or psychiatric impairments that in the Investigator's opinion will prevent administration or completion of protocol therapy