A Study of AB-218 in Patients With IDH1 Mutated Low Grade Glioma

NCT05577416 | Completed Early Phase 1

• 1 other identifier: 2022.003
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

Brief Summary

The aim of this clinical trial is to evaluate the feasibility of undertaking a Phase 0 surgical study in patients with diagnosis of a IDH1 mutated Low Grade Glioma (LGG) who have not received prior radiation or chemotherapy and are planned to undergo surgical resection.

Conditions

Glioma

Keywords

IDH1; Diffuse Astrocytoma; oligodendroglioma; phase 0; perioperative

Outcome Measures

Primary Outcomes (6)

• Phase 0: Feasibility of Phase 0 study in patient population

  Number of patients to complete all planned investigations and procedures

  14 months

• Phase 0: pharmacokinetic analysis of tumour tissue

  Total and unbound AB-218 in tumour tissue

  4 weeks

• Phase 0: pharmacokinetic analysis of cerebrospinal fluid (CSF)

  Total and unbound AB-218 in CSF

  4 weeks

• Phase 2: Number of Adverse events

  Number of adverse events (AEs) according to NCI CTCAE v 5

  up to 30 days after last study dose

• Phase 2: Incidence of drug related adverse events

  Drug related adverse events

  up to 30 days after last study dose

• Phase 2: Incidence of dose limiting toxicity

  Dose limiting toxicity events

  up to 30 days after last study dose

Secondary Outcomes (9)

• Phase 0: Incidence of treatment emergent Adverse events

  during 1 cycle of AB-128, prior to maximal resection (4 weeks)

• Phase 0: Safety of planned craniotomy and resection after stereotactic biopsy and treatment with AB-218

  30 days after maximal resection

• Phase 0: Pharmacodynamic (PD) analysis of AB-218 in tumour

  after maximal resection (4 weeks), at progression (optional)

• Phase 0: Pharmacodynamic (PD) analysis of AB-218 in cerebrospinal fluid (CSF)

  after maximal resection (4 weeks), at progression (optional)

• Phase 0: Pharmacodynamic (PD) analysis of AB-218 in plasma

  after maximal resection (4 weeks), monthly during treatment, at progression (optional)

Other Outcomes (5)

• Phase 2: Survival

  30 days after last study dose

• Phase 2: Survival

  30 days after last study dose

• Phase 2: Survival

  30 days after last study dose

Study Arms (1)

Safusidenib Erbumine (AB-218)

EXPERIMENTAL

Part A: Peri-operative treatment (Phase 0); Part B: Post operative adjuvant therapy (phase 2)

Procedure: Biopsy; Drug: Part A: Safusidenib Erbumine; Procedure: Surgery (maximal resection); Drug: Part B: Safusidenib Erbumine

Interventions

Biopsy PROCEDURE

Patients will undergo stereotactic biopsy by craniotomy or burr hole.

Safusidenib Erbumine (AB-218)

Part A: Safusidenib Erbumine DRUG

Part A: Safusidenib Erbumine orally 250 mg BID for 28 days.

Safusidenib Erbumine (AB-218)

Surgery (maximal resection) PROCEDURE

Surgery: Maximal safe resection, within 24 hours of last dose of Safusidenib Erbumine.

Safusidenib Erbumine (AB-218)

Part B: Safusidenib Erbumine DRUG

Part B: Safusidenib Erbumine orally 250 mg BID for 28 days for a minimum of 12, 28-day cycles subject to ongoing documented evidence of clinical benefit, until disease progression or unacceptable toxicity.

Safusidenib Erbumine (AB-218)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed LGG or new diagnosis of LGG based on MRI
• Tumours suitable for biopsy and safe for maximal resection in the opinion of the treating neurosurgeon
• Patients who in the consensus of the treating neurosurgeon require resection of the brain tumour.
• Patients who do not require immediate definitive resection of the brain tumour in the opinion of the treating neurosurgeon
• Measurable and/or evaluable disease as per LGG-RANO criteria
• Age ≥ 18 years of age.
• ECOG performance score 0-1
• Life expectancy of at least 24 months, in the opinion of the investigator
• Adequate haematological, renal and hepatic function
• Reproductive and contraception criteria as prescribed

You may not qualify if:

• Patients who meet any of the following criteria will be excluded from participation in the study:
• Patients who require immediate definitive resection due to degree of mass effect or symptoms
• Multicentric / multifocal tumour
• Tumour involves cerebellum or brainstem
• Patients who have undergone surgery for glioma within 24 months of study enrolment
• Patients who have received prior chemotherapy and / or radiation for a diagnosis of glioma
• Patients with contraindications to MRI or unwilling to undergo MRI
• History of central nervous system bleeding as defined by stroke within 6 months before enrolment
• Evidence of acute intracranial / intra-tumoural haemorrhage, except for participants with stable grade 1 haemorrhage
• Other general criteria including:
• i) ECG abnormalities ii) significant comorbidity or infection iii) Prior malignancy iv) Recent surgery v) Known allergy or sensitivity to any of the excipients in the investigational product vi) no contraindicated concomitant medications
• History or evidence of any other clinically significant disorder, condition or disease (with the exception of those outlined above) that, in the opinion of the investigator would pose a risk to participant safety or interfere with the study evaluation, procedures or completion

Sponsors & Collaborators

• Melbourne Health: lead
• Walter and Eliza Hall Institute of Medical Research: collaborator
• Nuvation Bio Inc.: collaborator

Study Sites (1)

Royal Melbourne Hospital

Melbourne, Victoria, Australia

Location

Related Publications (2)

• Drummond KJ, Spiteri M, Cain SA, Jones J, Shaya S, Topp M, Lu T, Tobler R, Valkovic AL, Moore Z, Fatunla OE, Kriel J, Moffet JJD, McAlpine H, Rosier M, Guan H, Dimou J, Schadewaldt V, Roberts-Thomson S, McArdle D, Lui E, Voelker-Albert M, di Sanzo S, Nijagal B, Narayana VK, Mitchell CB, Vissers JHA, Grimmond S, Rosenthal MA, Palmer LM, Best SA, Freytag S, Whittle JR. Perioperative IDH inhibition in treatment-naive IDH-mutant glioma: a pilot trial. Nat Med. 2025 Oct;31(10):3451-3463. doi: 10.1038/s41591-025-03884-4. Epub 2025 Aug 21.

  PMID: 40841487 DERIVED

• Cain SA, Topp M, Rosenthal M, Tobler R, Freytag S, Best SA, Whittle JR, Drummond KJ. A perioperative study of Safusidenib in patients with IDH1-mutated glioma. Future Oncol. 2024;20(33):2533-2545. doi: 10.1080/14796694.2024.2383064. Epub 2024 Aug 14.

  PMID: 39140289 DERIVED

MeSH Terms

Conditions

Glioma; Astrocytoma; Oligodendroglioma

Interventions

Biopsy; Surgical Procedures, Operative

Condition Hierarchy (Ancestors)

Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Specimen Handling; Diagnostic Techniques, Surgical; Investigative Techniques

Study Officials

• Kate Drummond, Prof

  Melbourne Health

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Phase 0 'window of opportunity'/perioperative (Part A) followed by Phase 2 adjuvant treatment

Study Record Dates

• First Submitted: September 19, 2022
• First Posted: October 13, 2022
• Study Start: October 11, 2022
• Primary Completion: March 26, 2025
• Study Completion: March 26, 2025
• Last Updated: March 18, 2026

Record last verified: 2026-03

Locations

AU (1)