DAY101 Granted Rare Pediatric Disease Designation by the FDA for Pediatric Low-Grade Glioma


The phase 2 clinical trial is currently recruiting patients with pediatric low-grade glioma to be treated with DAY101 following a rare pediatric disease designation by the FDA.

A rare pediatric disease designation has been granted by the FDA to DAY101 (formerly TAK 580 and MLN 2480) for the treatment of pediatric low-grade gliomas (pLGG), according to a press release from Day One.

There are currently no approved therapies or standard of care for pLGG, which, although rare, is the most common brain tumor diagnosed in pediatric patients. Should DAY101 receive a new drug application approval, Day One may receive a priority review voucher from the FDA, which will help to secure a priority review for marketing any application.

“Historical approaches to treating pLGG such as surgery, radiation, and chemotherapy are associated with significant acute and life-long adverse effects and new options are urgently needed,” Davy Chiodin, PharmD, chief development officer of Day One, said in a press release.

Single agent DAY101 has been investigated in over 250 patients and yielded a tolerable safety profile and promising anti-tumor activity in both pediatric and adult populations with certain MAPK pathway alterations. Additionally, preliminary results from the phase 1 PNOC014 trial (NCT03429803), which examined the agent in gliomas and other tumors, indicated that of 8 patients with relapsed, RAF fusion–positive pLGG, 2 achieved a complete response, 3 achieved partial responses, 2 achieved prolonged stable disease, and one experienced progressive disease.

DAY101 will be examined in the pivotal phase 2 FIREFLY-1 trial (NCT04775485), which is currently enrolling pediatric, adolescent, or young adult patients who have a known BRAF alteration.

The open label clinical trial will be comprised of approximately 60 patients who will be treated with DAY101 for a period of 26 cycles over the course of 24 months. DAY101 will be administered orally at the recommended phase 2 dose of 420 mg/m2 once weekly for each 28-day cycle. Patients are set to undergo radiographic evaluation at the end of every third cycle to evaluate disease progression.

DAY101 is an oral brain penetrant that is highly selective type 2 pan-RAF kinase inhibitor that was designed to target a key enzyme within the MAPK pathway.

The primary end point of the trial is overall response rate, with the secondary end points including safety and tolerability of DAY101 and relationship between pharmacokinetics and drug effects.

pLGG accounts for 30% to 50% of central nervous system tumors. BRAF wild-type fusions are the most common cancer-causing genomic alterations, and they can also be found in both adult and pediatric solid tumors. The only BRAF inhibitors that are currently approved are active in patients who harbor BRAF V600mutations and have demonstrated limited activity in brain tumors. Additionally, they cannot be utilized in patients who have BRAF fusions.

Some of the most common ways pLGG can impact patient quality of life is loss of vision and motor dysfunction. Although most patients with pLGG will survive their disease, those who cannot achieve a cure following surgery may face years of increasingly aggressive therapies that can have lasting effects on learning cognition and quality of life. Moreover, the indolent nature of pLGG means that patients may need to undergo many years of systemic therapy.

DAY101 was previously granted breakthrough therapy designation for the treatment of patients with pLGG harboring an active RAF alteration, need systemic therapy, and either progressed following prior treatment or have no other treatment options.

“DAY101 has the potential to become the first approved treatment option specifically for these patients. Receiving rare pediatric disease designation from the FDA underscores the critical value of our focus on pediatric indications at Day One and represents another significant milestone for the DAY101 program as we continue to enroll patients with pLGG in our pivotal phase 2 FIREFLY-1 study,” Chiodin concluded.


Day One receives FDA rare pediatric disease designation for DAY101 for the treatment of pediatric low-grad glioma. News Release. Day One. July 27, 2021. Accessed July 27, 2021.

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