FDA Grants Breakthrough Therapy Designation to Vorasidenib CDx in IDH1/2-Mutant Low-Grade Gliomas


"Breakthrough designation for the companion diagnostic is a big step forward in our endeavor to ensure that more clinicians can have quicker access to comprehensive genomic information."

The Oncomine Precision Assay has been granted a Breakthrough Therapy Designation by the FDA to detect isocitrate dehydrogenase (IDH) 1 and 2 mutations in patients with low-grade glioma who may be eligible for treatment with vorasidenib (AG-881), a first-in-class IDH1/IDH2 inhibitor, announced Thermo Fisher Scientific.1

"Access to timely, comprehensive genomic profiling data that supports well-informed treatment decisions can be challenging under the current cancer-testing paradigm," said Alain C. Mita, MD, associate professor of medicine, co-director of the Experimental Therapeutics Program at Cedars-Sinai Medical Center. "The possibility of having multi-biomarker profiling that is generated onsite and available in about a day is game-changing for the manner and speed in which oncologists are able to determine and prescribe the most appropriate treatment for their patients.

In the phase 3 INDIGO study (NCT04164901), the Oncomine Precision Assay is being further developed by way of a partnership between Thermo Fisher Scientific and Agios Pharmaceuticals. The study will evaluate the use of vorasidenib as treatment of patients with residual or recurrent grade 2 glioma with an IDH1/IDH2 mutation.1,2

Progression-free survival is the primary objective of INDIGO, and the secondary outcomes include the number of patients with adverse events, tumor growth rate, time to next intervention, objective response rate, time to response, duration of response, overall survival, and health-related quality of life.

Patients in the multicenter, randomized, double-blind, placebo-controlled trial will receive either continuous daily dosing of vorasidenib 40 mg or matching placebo. The study aims to enroll a total of 365 participants who are at least 12 years of age and weigh at least 40 kg. Patients are required to have grade 2 oligodendroglioma or astrocytoma per WHO 2016 criteria, have undergone at least 1 prior surgery for glioma, have confirmed IDH1 or IDH2 mutation, and disease that is MRI-evaluable, measurable and non-enhancing. If patients are 16 years or older, they must have a Karnofsky Performance Scale score of 80% or higher or a Lansky Play Performance Scale of at least 80% if they are under 16 years of age. Individuals who previously received prior anti-cancer therapy other than surgery and those with high-risk features will be excluded from the study.

INDIGO is actively recruiting patients who meet the study criteria and has a target study completion date of October 2024.

As a companion diagnostic (CDx) to vorasidenib, the Oncomine Precision Assay will run on the Ion Torrent Genexus System, the first next-generation sequencing (NGS) system that is completely automated and can deliver genomic profiling results in just 1 day. The assay is already a CDx for multiple other therapies and is approved as a liquid biopsy profiling assay for the detection of multiple types of lung and other solid tumors. In addition to IDH1/IDH2, the Ocomine Precision Assay maximizes the identification of guideline-recommended biomarkers including EGFRALKKRASBRAFROS1NTRKRETHER2, and others. Under the FDA’s Breakthrough Therapy Device Program, the assessment and review of the assay will be streamlined to give health care professionals timely access to the device.1

"Breakthrough designation for the companion diagnostic is a big step forward in our endeavor to ensure that more clinicians can have quicker access to comprehensive genomic information," said Garret Hampton, president of Clinical Next-Generation Sequencing and Oncology at Thermo Fisher Scientific. "Receiving this insight at the speed that the Genexus System enables can help expedite patient therapy selection, which is a critical need in the clinic today."


1. FDA grants Breakthrough Device Designation to Thermo Fisher Scientific's Oncomine Precision Assay to identify idh1 and idh2 mutations in low-grade glioma patients. News release. Carlsbad, California. June 15, 2020. Accessed June 15, 2020. https://bit.ly/2N1BJsd.

2. Thermo Fisher Scientific to co-develop a global companion diagnostic for low-grade glioma with Agios Pharmaceuticals. News release. Carlsbad, California. June 9, 2020. Accessed June 15, 2020. https://bit.ly/3frYi5K.

Related Videos
Related Content