Clinical trial

A Phase 1, Multicenter, Randomized, Controlled, Open-Label, Perioperative Study of AG-120 and AG-881 in Subjects With Recurrent, Non-Enhancing, IDH1 Mutant, Low Grade Glioma

Name

AG120-881-C-001

Description

Study to evaluate the suppression of 2-HG (2-hydroxyglutarate) in IDH-1 mutant gliomas in resected tumor tissue following pre-surgical treatment with AG-120 or AG-881.

Trial arms

Trial start

2018-03-20

Estimated PCD

2019-08-02

Trial end

2025-05-01

Status

Active (not recruiting)

Phase

Early phase I

Treatment

AG-120

Prior to surgery subjects will receive AG-120 administered continuously as a single agent dosed orally on Days 1 to 28 of a 28-day cycle. Subjects without residual disease following surgery will have the option to receive treatment for up to a year, until disease progression or unacceptable toxicity, whichever occurs first. Subjects with residual disease following surgery will have the option to receive treatment, until disease progression or unacceptable toxicity.

Arms:

AG-120

AG881

Prior to surgery subjects will receive AG-881 administered continuously as a single agent dosed orally on Days 1 to 28 of a 28-day cycle. Subjects without residual disease following surgery will have the option to receive treatment for up to a year, until disease progression or unacceptable toxicity, whichever occurs first. Subjects with residual disease following surgery will have the option to receive treatment, until disease progression or unacceptable toxicity.

Arms:

AG-881

Size

Primary endpoint

2-HG concentration in surgically resected tumors

Up to 4 weeks, on average

Eligibility criteria

Inclusion Criteria: 1. Be ≥18 years of age. 2. Have histologically or cytologically confirmed recurrent Grade 2 or 3 LGG (oligodendroglioma or astrocytoma according to World Health Organization 2016 classification). 3. Have documented IDH1 R132H gene mutation by local testing and known 1p19q or ATRX mutation status by local testing. 4. Have central confirmation of primarily non-enhancing disease by MRI with less than or equal to 5 mm slice thickness and up to 1 mm interslice gap on either 2D T2 weighted image, 3D T2 weighted image, or FLAIR, with at least 1 non-enhancing tumor measuring 1×1×1 cm. 5. Be candidates for clinical resection but for whom surgery is not urgently indicated (eg, for whom surgery within the next 2-4 months is appropriate). 6. Have KPS of ≥60% 7. Have expected survival of ≥12 months. Exclusion Criteria: 1. Have received prior systemic anti-cancer therapy within 1 month of the first dose of AG-120 or AG-881 or have received an investigational agent \<14 days prior to their first dose of AG-120 or AG-881. In addition, the first dose of AG-120 or AG-881 should not occur before a period of ≥5 half-lives of the investigational agent has elapsed. 2. Have had radiation within 6 months of the first dose of AG-120 or AG-881. (Note: Prior biopsy or surgery is allowed.) 3. Have received any prior treatment with an IDH inhibitor. 4. Have received any prior treatment with bevacizumab (Avastin).

Protocol

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE1'], 'designInfo': {'allocation': 'RANDOMIZED', 'interventionModel': 'PARALLEL', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'NONE'}}, 'enrollmentInfo': {'count': 49, 'type': 'ACTUAL'}}

Updated at

2024-02-26

1 organization

1 product

1 drug

1 indication

Organization

Institut de Recherches Internationales Servier

Drug

Ivosidenib

Indication

Glioma

Product

AG881