CTP-04. Safety and Feasibility of Tumor Treating Fields (TTFields) Combined with Temozolomide and Bevacizumab in Pediatric High-Grade Gliomas: Results from the HUMC1612 Phase I Trial

BACKGROUND Pediatric high-grade gliomas (HGG) are aggressive brain tumors with poor prognoses and limited effective treatment options. Tumor Treating Fields (TTFields) therapy is a noninvasive modality that uses low-intensity, intermediate-frequency alternating electric fields to disrupt mitosis in rapidly dividing tumor cells, sparing normal tissue. The Optune-Gio® NovoTTF-200A device delivers TTFields via transducer arrays placed on the scalp. The HUMC1612 Phase I study evaluated the safety and tolerability of combining TTFields with standard chemotherapy agents, temozolomide and bevacizumab, in children with newly diagnosed or recurrent HGG. METHODS Patients aged 5–18 years with HGG were enrolled following standard-of-care surgery and/or radiotherapy. The treatment protocol included 12 cycles (28 days each) of temozolomide (Days 1–5), bevacizumab (Days 1 and 15), and continuous TTFields therapy (minimum 18 hours/day). A 3 + 3 dose-escalation design of a single uniform treatment was used, with safety assessed during the first two cycles. RESULTS Six patients were evaluable (four newly diagnosed, two recurrent). No dose-limiting toxicities were observed. The most common Grade III/IV toxicities were chemotherapy-related hypertension (3 patients) and neutropenia (2 patients). Among newly diagnosed patients, mean treatment duration was 378 days (range 224–691). Three newly-diagnosed patients experienced progression after Cycles 8, 9, and 13. One newly-diagnosed patient completed 24 cycles and remains in remission more than five years post-diagnosis. Both patients with recurrent HGG progressed after two cycles. CONCLUSIONS The combination of TTFields with temozolomide and bevacizumab was safe and well-tolerated in pediatric patients with HGG. Early signs of efficacy in newly diagnosed patients are encouraging. Based on these findings, a larger Phase II study is planned to further evaluate this regimen in children with newly diagnosed HGG.