Targeting IDH1 and IDH2 Mutations

IDH mutations are considered driver mutations in the genetic evolution of low-grade glioma. Inhibiting these mutant proteins early in the disease course in low-risk patients who have undergone surgery only may suppress the growth and transformation of the disease.1,2

When IDH is mutated, it produces an excess amount of 2-HG, which is a substance
that is present in low levels in normal cells. When 2-HG is present in excessive
amounts, it results in changes within the cells, which may result in glioma.


About Vorasidenib

Vorasidenib is an investigational, orally available, brain-penetrant, potent inhibitor of IDH1 and IDH2 mutant proteins. In pre-clinical studies Vorasidenib has been demonstrated to reduce tumor 2-HG levels in mouse xenograft models, including an orthotopic glioma mouse model, by >96%; to reverse growth factor–independent growth in vitro; and to induce cellular differentiation in leukemia cell models. In Phase 1 studies, vorasidenib has an acceptable safety profile at doses of less than 100 mg and has demonstrated preliminary clinical activity, brain penetrance and suppression of tumor 2-HG, in patients with non-enhancing gliomas.3,4

The effectiveness and safety of vorasidenib have not been established. There is no guarantee that vorasidenib will receive health authority approval or become commercially available in any country for the use being investigated.

How to Participate

For more information regarding how to enroll your patient in the INDIGO Study:
Visit: https://clinicaltrials.gov/ct2/show/NCT04164901
Email: Agios Medical Information
Phone: 833-228-8474


INDIGO Study Overview5

Protocol Title

Clinical Study Protocol AG881-C-004: A Phase 3, Multicenter, Randomized, Double-blind, Placebo-controlled Study of Vorasidenib in Subjects with Residual or Recurrent Grade 2 Glioma With an IDH1 or IDH2 Mutation.

Pre-Screening

Subject will sign pre-screening consent to allow for central testing of IDH mutation status using banked tumor sample.

Screening Duration

Eligibility to be determined within 28 days prior to the start of study treatment on Cycle 1 Day 1 (C1D1).

Treatment Duration

Treatment in continuous 28-days (+/-2 days) cycles until radiographic disease progression, unacceptable toxicity, or until other discontinuation criteria are met.

Global Enrollment Goal

366 subjects


Study Design

Please see the INDIGO Study Record for the full set of inclusion and exclusion criteria.


Unblinding and Crossover5

Once radiographic progression of disease (PD) is confirmed, the subject and site staff will be unblinded to treatment assignment. Subjects who are determined to be receiving placebo upon unblinding after centrally confirmed radiographic PD, and who are not in need of immediate chemotherapy or radiotherapy, will have the option to cross over to receive vorasidenib, provided certain eligibility criteria are met.


How to Enroll Patients

To find current study sites and to learn how to enroll your patient, please see the INDIGO Study Site Locator.

Disclaimer

The effectiveness and safety of vorasidenib have not been established. There is no guarantee that vorasidenib will receive health authority approval or become commercially available in any country for the use being investigated.

References

  1. Yan H, Parsons DW, Jin G, et al. IDH1 and IDH2 Mutations in Gliomas. N Engl J Med. 2009; 360(8):765-773.
  2. Cancer Genome Atlas Research Network, Brat DJ, Verhaak RG, et al. Comprehensive, Integrative Genomic Analysis of Diffuse Lower-Grade Gliomas. N Engl J Med. 2015; 372(26):2481-2498.
  3. NCT02481154, Mellinghoff et al. Society of Neuro-oncology Annual Meeting 2018.
  4. NCT03343197, Mellinghoff et al. American Society of Clinical Oncology Annual Meeting 2019.
  5. Study of AG-881 in Participants With Residual or Recurrent Grade 2 Glioma With an IDH1 or IDH2 Mutation (INDIGO) – https://clinicaltrials.gov/ct2/show/NCT04164901