- FIREFLY-2 is the largest study ever conducted in front-line pLGG
- Trial aims to extend OJEMDA's indication beyond relapsed/refractory setting to address significant unmet need; topline data expected by mid-2027
BOSTON, May 8, 2026 /PRNewswire/ -- Day One Biopharmaceuticals, Inc., now part of Servier Group, today announced that it has completed enrollment in the FIREFLY-2 clinical trial, which is evaluating the efficacy, safety and tolerability of tovorafenib vs standard of care chemotherapy in the front-line setting of therapy for patients aged 6 months to 25 years with low-grade glioma. The trial is being conducted in collaboration with the European Society for Paediatric Oncology (SIOPe) Brain Tumor Group LOGGIC Consortium (LOGGIC). Tovorafenib, known as OJEMDATM, is currently indicated for treatment of patients 6 months of age and older with relapsed or refractory pediatric low-grade glioma (LGG) harboring a BRAF fusion or rearrangement, or BRAF V600 mutation.
"Reaching full enrollment in this trial is a critical step toward our goal of establishing OJEMDA as standard of care across all lines of therapy for individuals with BRAF-altered pLGG. By moving earlier in the treatment journey, we aim to intervene when we can have the greatest impact on the burden of this challenging cancer," said Elly Barry, M.D., Chief Medical Officer at Day One, now part of Servier Group. "Success in this study would not only further validate the efficacy and safety profile of OJEMDA, but also fundamentally evolve the pLGG treatment paradigm, and potentially establish a new standard of care for patients newly diagnosed with pLGG, the most common brain tumor afflicting children."
FIREFLY-2 is a Phase 3, global, randomized, multicenter, open-label study to evaluate the efficacy, safety, and tolerability of monotherapy tovorafenib, an oral, Type II RAF inhibitor, in patients ages 6 months to 25 years with RAF-altered pLGG requiring first-line systemic therapy. It is being conducted at approximately 140 sites across the U.S., Canada, Europe, Australia, South America, Middle East and Asia, and in just over three years has enrolled approximately 400 participants who are receiving either tovorafenib once weekly or one of four standard of care (SoC) chemotherapy regimens.
"Completing enrollment in FIREFLY-2 is a powerful early signal of momentum. It reflects what's possible when we bring together deep scientific expertise, a patient-first culture, and the scale to execute globally," said David K. Lee, CEO of Servier Pharmaceuticals. "So soon after Servier's acquisition of Day One, this milestone reinforces our conviction that joining forces was the right decision for patients and for our oncology strategy. As we aim to accelerate the development of targeted medicines and advance them with the rigor, speed and reach needed to make a meaningful difference, we hope this study helps unlock the potential to improve outcomes for children living with pediatric low-grade glioma."
The primary endpoint of the trial is overall response rate (ORR), including duration of response (DOR), based upon Response Assessment in Pediatric Neuro-Oncology Low-Grade Glioma (RAPNO-LGG) criteria, with key secondary endpoints including progression-free survival (PFS) and event-free survival (EFS) per RAPNO-LGG, time to next treatment (TTNT), overall survival (OS) and other measures, including patient-reported outcomes. The primary analysis is expected to occur approximately 12 months after the last patient is enrolled; preliminary insights are expected to be available in 2027. More information on the trial can be found at The FIREFLY-2 Trial - Day One Clinical Trials or https://clinicaltrials.gov/study/NCT05566795.
Media Contact
Darby Malkin
darby.malkin@servier.com
About tovorafenib
Tovorafenib (known as OJEMDATM in the U.S.) is a Type II RAF kinase inhibitor of mutant BRAF V600, wild-type BRAF, and wild-type CRAF kinases. Tovorafenib is indicated for the treatment of patients 6 months of age and older with relapsed or refractory pediatric low-grade glioma (LGG) harboring a BRAF fusion or rearrangement, or BRAF V600 mutation. This indication is approved under accelerated approval based, in part, on response rate and duration of response according to multiple response assessment criteria: Response Assessment in Neuro-Oncology High-Grade Glioma (RANO-HGG) criteria, Response Assessment in Pediatric Neuro-Oncology Low-Grade Glioma (RAPNO LGG) criteria, and Response Assessment for Neuro-Oncology Low-Grade Glioma (RANO LGG) criteria. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).
Tovorafenib was granted Breakthrough Therapy and Rare Pediatric Disease designations by the FDA for the treatment of patients with pLGG harboring an activating RAF alteration, and it was evaluated by the FDA under priority review. Tovorafenib has also received Orphan Drug designation from the FDA for the treatment of malignant glioma and from the European Commission for the treatment of glioma.
Please see full prescribing information including important safety information about OJEMDA at www.OJEMDA.com.
About Pediatric Low-Grade Glioma
Pediatric low-grade gliomas (pLGG) are the most common brain tumor with an estimated US incidence of 1,100 and Europe incidence of 700 children per year who are eligible for front-line systemic therapy.i, ii BRAF is the gene most commonly altered in pLGG, which includes two primary types of BRAF alterations – a BRAF gene fusion and BRAF point mutation. These BRAF alterations account for >50% of pLGG cases worldwide and prior to the introduction of OJEMDA, there were no approved treatments for people with pLGG driven by BRAF fusions.i, iii
Pediatric low-grade gliomas can be chronic and relentless, with patients suffering profound side effects from both the tumor and the treatment, which may include chemotherapy and radiation. These side effects can impact their life over the long term, and may include motor deficiencies, vision loss, hormone deficiency and alterations in growth and development. Most children with pLGG will survive their cancer, but for the majority of those in whom a complete surgical resection is not possible, these tumors tend to recur frequently throughout childhood, necessitating multiple treatments. The cumulative toxicity of numerous therapies, along with the damage caused by multiple episodes of tumor progression, take a significant toll on the children and their families.
About Servier in Oncology
Servier is a global leader in oncology, governed by a non-profit foundation. Servier approaches innovation with a long-term vision, free of influence from fiduciary responsibilities.
Servier is the leader in IDH-mutant targeted therapies and devotes more than 65% of its research and development budget to Oncology. Servier aspires to advance more targeted therapies by identifying mutations and understanding how these mutations impact cancer and its progression. Servier believes we can serve more people by helping the right patients find the right treatment, at the right time.
Servier takes a One Innovation Engine approach to R&D and is actively seeking alliances, partnerships and acquisitions at various stages of the portfolio.
For more information about working with Servier to bring the promise of tomorrow to the patients it serves, visit Servier.us.
Important Safety Information
Before taking or giving OJEMDA, tell your healthcare provider about all of your or your child's medical conditions, including if you:
- have bleeding, skin, or liver problems
- are pregnant or plan to become pregnant. OJEMDA can harm your unborn baby.
Females who are able to become pregnant:
- You should use effective non-hormonal birth control (contraception) during treatment with OJEMDA and for 28 days after your last dose of OJEMDA.
Males with female partners who are able to become pregnant should use effective non-hormonal birth control (contraception) during treatment with OJEMDA and for 2 weeks after your last dose of OJEMDA.
- are breastfeeding or plan to breastfeed. Do not breastfeed during treatment and for 2 weeks after your last dose of OJEMDA.
Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.
What should I avoid while taking OJEMDA?
Limit the amount of time you spend in sunlight. OJEMDA can make your skin sensitive to the sun (photosensitivity). Use sun protection measures, such as sunscreen, sunglasses and wear protective clothes that cover your skin during your treatment with OJEMDA.
What are the possible side effects of OJEMDA?
OJEMDA may cause serious side effects, including:
- bleeding problems (hemorrhage) are common and can also be serious. Tell your healthcare provider if you have any signs or symptoms of bleeding, including:
- headache, dizziness or feeling weak
- coughing up blood or blood clots
- vomiting blood or your vomit looks like "coffee grounds"
- red or black stools that look like tar
- skin reactions, including sensitivity to sunlight (photosensitivity). OJEMDA can cause skin reactions that can become severe. Tell your healthcare provider if you get new or worsening skin reactions, including:
- rash
- bumps or tiny papules
- acne
- peeling, redness, or irritation
- blisters
- liver problems. Your healthcare provider will do blood tests to check your liver function before and during treatment with OJEMDA. Tell your healthcare provider right away if you develop any of the following symptoms:
- yellowing of your skin or your eyes
- dark or brown (tea-colored) urine
- nausea or vomiting
- loss of appetite
- tiredness
- bruising
- bleeding
- pain in your upper right stomach area
- slowed growth in children. Growth will be checked routinely during treatment with OJEMDA.
The most common side effects of OJEMDA include:
- rash
- hair color changes
- tiredness
- viral infection
- vomiting
- headache
- fever
- dry skin
- constipation
- nausea
- acne
- upper respiratory tract infection
OJEMDA may cause fertility problems in males and females, which may affect your ability to have children.
These are not all the possible side effects of OJEMDA. Call your healthcare provider for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. You may also report side effects to Day One Biopharmaceuticals at 1-877-204-2820.
Please see full Patient Information, including Instructions for Use for more information.
Disclosures
This release contains general information about the Servier Group and its entities (hereinafter "Servier and its Affiliates") and is intended for informational purposes only. The information is thought to be reliable; however, Servier and its Affiliates make no representation as to the accuracy or completeness of the information contained herein or otherwise provided and accept no responsibility or liability, in contract, in tort, in negligence, or otherwise, should the information be found to be inaccurate or incomplete in any respect.
Servier and its Affiliates are not acting as an advisor to the recipient of this information, and the ultimate decision to proceed with any transaction rests solely with the recipient of this information. Therefore, prior to entering into any proposed transaction, the recipient of this information should determine, without reliance upon Servier or its Affiliates, the economic risks and merits, as well as the legal, tax, and accounting characterizations and consequences, of the transaction and that it is able to assume these risks.
This statement also contains forward-looking statements that are subject to varying levels of uncertainty and risk. Investigational new drugs and indications are subject to further scientific and medical review and regulatory approval. They are not approved for use by the FDA.
Any reliance placed on this document is done entirely at the risk of the person placing such reliance. The information contained in this document is neither an offer to sell nor the solicitation of an offer to enter into a transaction.
The content of this document is a summary only, is not complete, and does not include all material information about Servier and its Affiliates, including potential conflicts of interest.
To the maximum extent permitted by applicable laws and regulations, Servier and its Affiliates disclaim all representations, warranties, conditions and guarantees, whether express, implied, statutory or of other kind, nor does it accept any duty to any person, in connection with this document. Without prejudice to the generality of the foregoing, Servier and its Affiliates do not warrant or represent that the information or opinions contained in this document is accurate or complete.
To the maximum extent permitted by applicable laws and regulations, Servier and its Affiliates shall not be liable for any loss, damage or expense whatsoever, whether direct or indirect, howsoever arising, whether in contract, tort (including negligence), strict liability or otherwise, for direct, indirect, incidental, consequential, punitive or special damages arising out of or in connection with this document, including (without limitation) any course of action taken on the basis of the same. The estimates, strategies, and views expressed in this document are based upon past or current data and information and are subject to change without notice.
[i] Ryall S, et al. Acta Neuropathol Commun. 2020;8(1):30.
[ii] Estimates of annual incidence and prevalence for addressable patient population in E.U. 4 + U.K. are based on Ipsen calculations from publicly available data (Eurostat, <25yo population; Global Burden of Disease 2019; Desandes et al. Incidence and survival of children with central nervous system primitive tumors in the French National Registry of Childhood Solid Tumors. Neuro Oncol. 2014 Jul;16(7):975-83. doi: 10.1093/neuonc/not309; Qaddoumi et al. Outcome and prognostic features in pediatric gliomas: a review of 6212 cases from the Surveillance, Epidemiology, and End Results database. Cancer. 2009 Dec 15;115(24):5761-70. doi: 10.1002/cncr.24663)
[iii] Traunwieser T, et al. Neurooncol Adv. 2020;2(1):vdaa094.
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