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

This trial will study the effectiveness of ACT001 in adult patients whose Glioblastoma have recurred with a STAT3-high signature after standard-of-care treatment with at least radiation therapy.

Study Overview

• Status: Suspended
• Conditions: Recurrent Glioblastoma
• Intervention / Treatment: Drug: ACT001

• Study Type: Interventional
• Enrollment (Estimated): 12
• Phase: Phase 2

Contacts and Locations

Study Locations

• Singapore
  • Singapore, Singapore
    • National Neuroscience Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ACT001	Drug: ACT001; Patients recruited and have signed informed consent will be initiated on ACT001 400mg twice a day. Treatment course will repeat every 28 days in the absence of disease progression or unacceptable toxicity

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Response Rate	ORR as defined as radiographic complete response, or partial response, or stable disease. Patients with stable disease will be considered responders if disease is stable for 24 weeks or more. The regimen will be considered worthy of further study if responses as defined above are observed in at least 3 of the 12 patients.	1.5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival (PFS) & Overall survival (OS)	6 months progression-free survival (PFS), defined as proportion of patients who remained alive and progression-free at 6 months. PFS, which is defined as time from study enrolment to progression of disease per RANO criteria, or death, whichever occurs first. For patients who are not documented to have experienced a PFS event at the time of an analysis, PFS will be right-censored on the date of their last adequate assessment of disease. Overall survival (OS), which is defined as time from study enrolment to death from any cause. For patients who are not reported to have died at the time of an analysis, OS will be right-censored at the last date the patient is documented to be alive.	1.5 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Toxicity evaluation	Study team will assess adverse events, laboratory data and vital signs throughout the study. Analyses of adverse events will include only "treatment-emergent" events, i.e., those that start or worsen on or after the day of the first dose of study drug. Adverse event severity and laboratory evaluation changes will be assessed by utilizing National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0. Adverse events will be summarized by preferred terms within a System and Organ Class according to the most current Medical Dictionary for Regulatory Activities (MedDRA) dictionary. Changes from baseline will be analyzed for each scheduled post-baseline visit and for the final visit for blood chemistry and hematology parameters, as well as urinalysis and vital sign parameters. Shifts in laboratory values from baseline NCI CTCAE grades to maximum and final post-baseline grades will be assessed.	1.5 years
Drug levels	Drug levels in cerebrospinal fluid and tissue sample when available in patients who are agreeable to proceed with Omaya shunt insertion, lumbar puncture or undergoes further surgical resection following treatment with ACT001.	1.5 years
Treatment response and resistance	Tissue and blood exosome biomarkers that are predictive of treatment response and treatment resistance.	1.5 years

Collaborators and Investigators

• Sponsor: National Neuroscience Institute

Study record dates

Study Major Dates

• Study Start (Actual): March 22, 2025
• Primary Completion (Estimated): May 1, 2026
• Study Completion (Estimated): May 1, 2026

Study Registration Dates

• First Submitted: November 27, 2024
• First Submitted That Met QC Criteria: March 24, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): April 20, 2026
• Last Update Submitted That Met QC Criteria: April 15, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioblastoma; ACT001
• Other Study ID Numbers: 2024-3595

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No