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

A Phase 0/2 Study of AB-218 in Patients With IDH1 Mutated Low Grade Glioma

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.

This is a single arm, open label Phase 0 trial to assess the feasibility, pharmacokinetics and pharmacodynamics of treatment with AB-218 following biopsy and prior to resection in patients with IDH1 mutated glioma.

Participants will receive treatment in 2 parts:

Part A: Biopsy followed by 1 cycle (28 days) of Safusidenib Erbumine (formerly AB-218), an orally available, small molecular inhibitor of mutated IDH1, then safe maximal resection of the tumour.

Part B: Following recovery from surgery, patients will receive at least 12 cycles of Safusidenib, subject to ongoing documented evidence of clinical benefit, until disease progression or unacceptable toxicity.

It is expected that 15 patients will take part in this study.

It is anticipated this research study will enable investigators to objectively measure the biological activity of Safusidenib in patients with IDH1 mutated LGG.

Anti-tumour activity will be assessed by RANO response criteria.

The investigators have previous experience in pre-treating patients with GBM prior to surgery with systemic therapies and collecting tumour, peri-tumour and normal brain tissues for PK, PD and biomarker evaluation

Inclusion Criteria:

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

Exclusion Criteria:

Patients who meet any of the following criteria will be excluded from participation in the study:

1. Patients who require immediate definitive resection due to degree of mass effect or symptoms

2. Multicentric / multifocal tumour

3. Tumour involves cerebellum or brainstem

4. Patients who have undergone surgery for glioma within 24 months of study enrolment

5. Patients who have received prior chemotherapy and / or radiation for a diagnosis of glioma

6. Patients with contraindications to MRI or unwilling to undergo MRI

7. History of central nervous system bleeding as defined by stroke within 6 months before enrolment

8. Evidence of acute intracranial / intra-tumoural haemorrhage, except for participants with stable grade 1 haemorrhage

9. 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

10. 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