A phase 3, multicenter, randomized, double-blind, placebo-controlled study of AG-881 in subjects with residual or recurrent grade 2 glioma with and IDH1 or IDH2 mutatio

Phase 3

Recruiting

• Conditions: Glioma; 10029211

• Registration Number: NL-OMON54490
• Lead Sponsor: Institut de Recherches Internationales Servier I.R.I.S

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Last Update Posted: 9 September 2024

Recruitment & Eligibility

• Status: Recruiting
• Sex: Not specified
• Target Recruitment: 32

Inclusion Criteria

1. Be at least 12 years of age and weigh at least 40 kg.
3. Have Grade 2 oligodendroglioma or astrocytoma per WHO 2016 criteria.
4. Have had at least 1 prior surgery for glioma (biopsy, sub-total resection,
gross-total resection), with the most recent surgery having occurred at least 1
year (-1 month) and not more than 5 years (+3 months) before the date of
randomization, and no other prior anticancer therapy, including chemotherapy
and radiotherapy and not be in need of immediate chemotherapy or radiotherapy
in the opinion of the Investigator.
5. Have confirmed IDH1 (IDH1 R132H/C/G/S/L mutation variants tested) or IDH2
(IDH2 R172K/M/W/S/G mutation variants tested) gene mutation status disease by
central laboratory testing during the Prescreening period and available 1p19q
status by local testing (eg, fluorescence in situ hybridization [FISH],
comparative genomic hybridization [CGH] array, sequencing) using an accredited
laboratory.
6. Have MRI-evaluable, measurable, non-enhancing disease, as confirmed by the
BIRC, assessed at Screening on 2D T2-weighted or 2D T2-weighted
fluid-attenuated inversion recovery (FLAIR) MRI with <=4 mm slice thickness and
no interslice gap. Measurable non-enhancing disease is defined as at least 1
target lesion measuring >=1 cm × >=1 cm (bidimensional). Centrally confirmed,
minimal, non-nodular, and non-measurable enhancement that has not changed
between the 2 most recent scans (including screening scan) will be permitted.
7. Have a KPS (Appendix 11.7) score (for subjects >=16 years of age) or LPPS
(Appendix 11.6) score (for subjects <16 years of age) of >=80%.
8. Have expected survival of >=12 months.
9. Have adequate bone marrow function
10. Have adequate hepatic function
11. Have adequate renal function
12. Have recovered from any clinically relevant toxicities associated with any
prior surgery for the treatment of glioma unless stabilized under medical
management.

For the complete and extended list, see protocol section 4.2 Inclusion Criteria

Exclusion Criteria

1. Have had any prior anticancer therapy other than surgery (biopsy, sub-total
resection, gross-total resection) for treatment of glioma including systemic
chemotherapy, radiotherapy, vaccines, small-molecules, IDH inhibitors,
investigational agents, laser ablation etc.
2. Have features assessed as high-risk by the Investigator, including brainstem
involvement either as primary location or by tumor extension, clinically
relevant functional or neurocognitive deficits due to the tumor in the opinion
of the Investigator (deficits resulting from surgery are allowed), or
uncontrolled seizures (defined as persistent seizures interfering with
activities of daily life AND failed 3 lines of antiepileptic drug regimens
including at least 1 combination regimen).
3. Concurrent active malignancy except for a) curatively resected nonmelanoma
skin cancer or b) curatively treated carcinoma in situ. Subjects with
previously treated malignancies are eligible provided they have been
disease-free for 3 years at Screening.
4. Are pregnant or breastfeeding.
5. Have an active infection that requires systemic anti-infective therapy or
with an unexplained fever >38.5°C within 7 days of C1D1.
6. Have a known hypersensitivity to any of the components of AG-881.
7. Have significant active cardiac disease within 6 months before the start of
study treatment, including New York Heart Association Class III or IV
congestive heart failure (Appendix 11.2), myocardial infarction, unstable
angina, and/or stroke.
8. Have LVEF <40% by echocardiogram (ECHO) (or by other methods according to
institutional practice) obtained within 28 days before the start of study
treatment.
9. Have a heart-rate corrected QT interval using Fridericia*s formula (QTcF)
>=450 msec or other factors that increase the risk of QT prolongation or
arrhythmic events (eg, heart failure, hypokalemia, family history of long QT
interval syndrome). Subjects with bundle branch block and prolonged QTcF are
permitted with approval of the Medical Monitor.
10. Are taking therapeutic doses of steroids for signs/symptoms of glioma.
Subjects taking physiologic doses (defined as equivalent of <=10 mg prednisone
daily) for medical conditions not related to glioma will be permitted.
11. Exclusion Criterion 11 removed in Protocol Amendment 1 (v2.0).
12. Are taking any medications that are CYP3A or CYP2C9 substrates with a
narrow therapeutic index as listed in Appendix 11.4. (Subjects should be
transferred to other medications before receiving the first dose of study drug.)
13. Have known active hepatitis B virus (HBV) or hepatitis C virus (HCV)
infection, known positive human immunodeficiency virus antibody results, or
AIDS-related illness. Subjects with a sustained viral response to HCV treatment
or immunity to prior HBV infection will be permitted. Subjects with chronic HBV
that is adequately suppressed by institutional practice will be permitted.
14. Have known active inflammatory gastrointestinal disease, chronic diarrhea,
previous gastric resection or lap band dysphagia, short-gut syndrome,
gastroparesis, or other condition that limits the ingestion or gastrointestinal
absorption of drugs administered orally. Gastroesophageal reflux disease under
medical treatment is allowed (assuming no drug interaction potential).
15. Have any other ac

Study & Design

• Study Type: Interventional
• Study Design: Not specified