A Phase 1 trial of iron metabolism-targeting oral gallium maltolate in recurrent and refractory glioblastoma

Background Gallium maltolate is an oral compound that disrupts iron-dependent glioblastoma (GBM) growth and prolongs survival in animal models. This Phase 1 trial of oral gallium maltolate in patients with recurrent GBM was conducted to assess toxicity, determine a recommended Phase 2 dose (RP2D), and seek signals of tumor response. Methods Using a 3 + 3 dose-escalation design with 5 drug dose levels of oral gallium maltolate (500—2,500 mg daily), 24 patients received a minimum of one 4-week cycle to assess toxicity, and 22 patients of these patients received a minimum of 2 cycles to assess tumor response. Patients with stable disease on MRI at 8 weeks continued treatment until progression. Results Grade 1 or 2 adverse effects of diarrhea, anorexia, nausea, and fatigue occurred in 24 patients. The RP2D was determined by considering diarrhea requiring treatment and serum gallium levels that plateaued at doses of 2,000—2,500 mg/day. ALT elevation occurred in 1 patient each on 1,000 and 2000 mg/day. RBC MCV decreased below normal during treatment in 9 patients. Nephrotoxicity was not seen. GBM progressed in 11 of 22 evaluable patients after 2 cycles and in 6 following 3—6 cycles. Three patients progressed after 8, 10, and 26 cycles. One patient with a stable partial response remains on treatment after 33 cycles. The median overall survival was 16 months. Conclusions Oral gallium maltolate is safe and well-tolerated with an RP2D of 2,000 mg/day. Further investigation to assess the clinical efficacy of gallium maltolate in GBM is warranted.