SUMMARY

• No data regarding the pharmacokinetics (PK) of BALVERSA blood-brain barrier (BBB) or central nervous system (CNS) penetration were identified in the published literature.
• No data regarding the use of BALVERSA in patients with urothelial carcinoma and baseline CNS metastases were identified in published literature.
• RAGNAR (NCT04083976) is an ongoing, phase 2, open-label, single-arm, multicenter study evaluating the efficacy and safety of BALVERSA in adult and pediatric patients (children aged ≥6 years) with unresectable, locally advanced, or metastatic solid tumor malignancies, fibroblast growth factor receptor (FGFR) mutations or gene fusions, and documented disease progression. Patients must have received ≥1 prior line of systemic therapy in the advanced, unresectable, or metastatic setting; or be a child or adolescent with a newly diagnosed solid tumor and no acceptable standard therapies. The study enrolled 316 patients.^1,2 For complete study details, refer to https://www.clinicaltrials.gov/ct2/show/NCT04083976.
  • A total of 191 patients fulfilled the primary analysis molecular eligibility criteria, of whom 110 patients were enrolled. Preliminary results of molecular eligibility screening for the RAGNAR study included 19% (21/110) of patients with high-grade glioma (FGFR3 fusion [95%] with FGFR3-TACC3 fusion as the most frequent variant) and 2% (2/110) of patients with low-grade glioma (FGFR1 mutation [100%] with FGFR1-K656E mutation as the most frequent variant).³
  • Pant et al (2023)⁴ presented primary analysis results after a median follow-up of 17.9 months from a cohort of patients (n=217) with 16 different solid tumor types in the RAGNAR study. For 30 patients with high-grade glioma, the objective response rate (ORR) was 10% and the disease control rate (DCR) was 57%. For 7 patients with low-grade glioma, the ORR was 29% and the DCR was 71%. The most common treatment-emergent adverse events (TEAEs) were hyperphosphatemia, stomatitis, diarrhea, and dry mouth. Safety was not separately evaluated for patients with gliomas.
• A phase 1 study of BALVERSA in 187 patients with advanced or refractory solid tumors, including glioblastoma (GBM; 7%; 13/187), reported PK/pharmacodynamic (PD), safety and efficacy data for the evaluable study population.^5,6
• In a preclinical study, BALVERSA inhibited growth of glioma cells harboring FGFR (FGFR3‐TACC3) fusions in vitro and in vivo. A preliminary report of preclinical activity included 2 patients with glioma harboring this genetic alteration exhibited stable disease and a minor response, respectively, when treated with BALVERSA.⁷

Literature Search

A literature search of MEDLINE^®, Embase^®, BIOSIS Previews^®, and Derwent Drug Files (and/or other resources, including internal/external databases) was conducted on 06 June 2024.