Dddr-29. targeting fgfr fusions: a case of catequentinib (al3818) and temozolomide combination therapy for recurrent mgmt methylated tacc-fgfr fusion positive glioblastoma

Abstract BACKGROUND There is no gold-standard for the management of recurrent glioblastoma (GBM). However, advances at the interface of molecular testing and rational drug design have opened avenues for personalized medicine. Here we describe the case of a 52-year-old patient with recurrent GBM (WHO grade 4) with known FGFR3-TACC3 fusion and MGMT promoter methylation by Caris molecular profiling. Initial treatment included radiotherapy with concomitant and adjuvant temozolomide. However, after 18 months off therapy, the patient became clinically and radiographically progressive with multifocal disease. Herein, we describe our experience with temozolomide and catequentinib (AL3818) in a single patient. METHODS We reviewed the available literature on targeting FGFR3-TACC3 fusion positive glioblastoma with catequentinib (1-[[[4-(4-fluoro-2-methyl-1H-indol-5-yloxy)-6-methoxyquinolin-7-Yl] oxy] methyl] cyclopropanamine dihydrochloride). Catequentinib is an oral small-molecule pan-kinase inhibitor with selective VEGFR2 inhibition, it is under investigation in multiple phase 2 and 3 clinical trials and can safely be administered concomitantly with temozolomide. We obtained single-patient Investigational New Drug (IND) approval and free drug was shipped directly from the manufacturer (Advenchen Laboratories; Jiangsu Chia-Tai Tianqing Pharmaceutical) to our institution’s investigational chemotherapy pharmacy. We administered catequentinib 12 mg by mouth for 14 days on and 7 days off of a 21-day cycle along with temozolomide 50mg/m2/day of a 28-day cycle with routine monitoring of laboratory parameters. RESULTS The combination of temozolomide and catequentinib was well-tolerated, resulted in clinical stability, and partial radiographic response at 3-month follow-up. CONCLUSION Catequentinib in combination with metronomic temozolomide was well tolerated in this single patient. This patient’s response shows the promise of intentional, patient-specific care at the intersection of molecular testing and rational drug design. The patient will continue therapy and updated clinical and radiographic outcomes will be presented.