In a phase I study reported in the Journal of Clinical Oncology, Mellinghoff et al found that ivosidenib was well tolerated in patients with IDH1-mutant advanced glioma and was associated with prolonged disease control in those with nonenhancing glioma.
Study Details
The study included 66 evaluable patients from 12 sites in the United States and 1 in France. Thirty-five patients had nonenhancing glioma on magnetic resonance imaging, and 31 had enhancing glioma. In the dose-escalation phase, no dose-limiting toxicities were observed and maximum tolerated dose was not reached, with a dose of 500 mg once daily being selected for the expansion cohort.
“In patients with IDH1[-mutant] advanced glioma, ivosidenib [at] 500 mg once per day was associated with a favorable safety profile, prolonged disease control, and reduced growth of nonenhancing tumors.”— Mellinghoff et al
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Key Findings
Among the 35 patients with nonenhancing glioma, objective response (partial response) was observed in 1 patient (2.9%), with 30 additional patients (85.7%) having stable disease. Among the 31 patients with enhancing glioma, no objective responses were observed, with stable disease being achieved in 14 (45.2%).
Among patients with measurable disease at baseline, tumor measurements decreased from baseline in 22 (66.7%) of 33 with nonenhancing tumors and in 9 (33.3%) of 27 with enhancing tumors.
Median progression-free survival was 13.6 months (95% confidence interval [CI] = 9.2–33.2 months) in the nonenhancing cohort and 1.4 months (95% CI = 1.0–1.9 months) in the enhancing cohort.
An exploratory analysis among 24 patients in the nonenhancing cohort showed that estimated tumor growth rate per 6 months was 26% in the pretreatment period vs 9% after ivosidenib treatment was initiated; the estimated percentage change in growth rate for after vs before treatment was –14%.
Grade ≥ 3 adverse events were observed in 13 patients (19.7%), including headache (4.5%), hypophosphatemia (3.0%), and seizure (3.0%); events were considered treatment-related in two patients (neutropenia, decreased weight, hyponatremia, and arthralgia). Serious adverse events were reported in 11 patients (16.7%), with none considered related to treatment. No patients discontinued treatment due to an adverse event.
The investigators concluded, “In patients with IDH1[-mutant] advanced glioma, ivosidenib [at] 500 mg once per day was associated with a favorable safety profile, prolonged disease control, and reduced growth of nonenhancing tumors.”
Ingo K. Mellinghoff, MD, of the Department of Neurology and Human Oncology & Pathogenesis Program, Memorial Sloan Kettering Cancer Center, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by Agios Pharmaceuticals. Translational research studies were supported by National Institutes of Health grants and the National Brain Tumor Society
Defeat GBM Initiative. For full disclosures of the study authors, visit ascopubs.org.
