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

Prior treatment

• Previous or current treatment with a JAK or STAT3 inhibitor
• Previous or current treatment with bevacizumab/VEGF inhibitor

Other illness

• Presence of extracranial metastatic or leptomeningeal disease
• 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

Other

• Patient is a lactating or pregnant female.

• 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.