Clinical trial · Interventional
DAY101 vs. Standard of Care Chemotherapy in Pediatric Participants With Low-Grade Glioma Requiring First-Line Systemic Therapy (LOGGIC/FIREFLY-2)
LOGGIC/FIREFLY-2: A Phase 3, Randomized, International Multicenter Trial of DAY101 Monotherapy Versus Standard of Care Chemotherapy in Patients With Pediatric Low-Grade Glioma Harboring an Activating RAF Alteration Requiring First-Line Systemic Therapy
- Source
- ClinicalTrials.gov
- Retrieved
- Sep 8, 2026
- Layer
- normalized (units and labels harmonized; values unchanged)
- Run
- ING-CLINICALTRIALS-20260908-000001
Summary
Brief summary (as posted)
This is a 2-arm, randomized, open-label, multicenter, global, Phase 3 trial to evaluate the efficacy, safety, and tolerability of tovorafenib monotherapy versus standard of care (SoC) chemotherapy in participants with pediatric low-grade glioma (LGG) harboring an activating rapidly accelerated fibrosarcoma (RAF) alteration requiring first-line systemic therapy.
Conditions
Conditions (3)
Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.
| Condition (as posted) | Mapped entity | Match | Confidence |
|---|---|---|---|
| Low-grade Glioma | Low Grade Glioma | ONTOLOGY_EXACT | 0.98 |
| Pediatric Low-grade Glioma | Childhood Low Grade Glioma | ALIAS | 0.90 |
| Rapidly Accelerated Fibrosarcoma (RAF) Altered Glioma | — | UNRESOLVED | — |
Interventions
Interventions (2)
| Intervention | Type | Mapped drug | Match |
|---|---|---|---|
| Chemotherapeutic Agent | Drug | — | UNRESOLVED |
| Tovorafenib | Drug | Tovorafenib | ALIAS |
Design
Arms and outcomes
Arms (2)
- type
- EXPERIMENTAL
- label
- Tovorafenib
- interventionNames
- Drug: Tovorafenib
- type
- ACTIVE_COMPARATOR
- label
- Investigator's choice of Standard of care therapy
- interventionNames
- Drug: Chemotherapeutic Agent
Primary outcomes (1)
- measure
- Objective response rate (ORR) of tovorafenib monotherapy versus SoC chemotherapy
- timeFrame
- Up to 60 months
- description
- ORR assessed per Response Assessment in Pediatric Neuro Oncology (RAPNO) criteria by Independent Review Committee (IRC), and defined as the proportion of participants with overall confirmed response of complete response (CR), partial response (PR), or minor response (MR).
Eligibility
Eligibility (as posted)
- Sex
- All
- Maximum age
- 25 Years
Show eligibility criteria text
Inclusion Criteria: * Less than 25 years of age with LGG with known activating RAF alteration. * Histopathologic diagnosis of glioma or glioneuronal tumor. * At least one measurable lesion as defined by RANO criteria. * Meet indication for first-line systemic therapy. Exclusion Criteria: * Participant has any of the following tumor-histological findings: 1. Schwannoma 2. Subependymal giant cell astrocytoma (Tuberous Sclerosis) 3. Diffuse intrinsic pontine glioma, even if histologically diagnosed as World Health Organization (WHO) Grade I-II * Participant's tumor has additional pathogenic molecular alterations, including but not limited to a) isocitrate dehydrogenase (IDH) 1/2 mutation, b) Histone H3 mutation, and c) neurofibromatosis Type 1 (NF-1) loss of function alteration. * Known or suspected diagnosis of NF-1/ neurofibromatosis Type 2 (NF-2). * Prior or ongoing nonsurgical anticancer therapy for this indication (eg, chemotherapy, oral/IV targeted therapy) including radiation.
References
Publications (2)
- DERIVEDAmayiri N, Mushtaq N, Ghalibafian M, Bouffet E. Management of pediatric brain tumors in low- and middle-income countries. Adv Cancer Res. 2025;167:427-453. doi: 10.1016/bs.acr.2025.08.004. Epub 2025 Sep 9. PMID 41198344
- DERIVEDvan Tilburg CM, Kilburn LB, Perreault S, Schmidt R, Azizi AA, Cruz-Martinez O, Zapotocky M, Scheinemann K, Meeteren AYNS, Sehested A, Opocher E, Driever PH, Avula S, Ziegler DS, Capper D, Koch A, Sahm F, Qiu J, Tsao LP, Blackman SC, Manley P, Milde T, Witt R, Jones DTW, Hargrave D, Witt O. LOGGIC/FIREFLY-2: a phase 3, randomized trial of tovorafenib vs. chemotherapy in pediatric and young adult patients with newly diagnosed low-grade glioma harboring an activating RAF alteration. BMC Cancer. 2024 Jan 30;24(1):147. doi: 10.1186/s12885-024-11820-x. PMID 38291372