Vorasidenib shows promise in IDH-mutant lower grade gliomas

In patients with recurrent or progressive lower grade gliomas (LGGs) harbouring mutations in the genes encoding isocitrate dehydrogenase 1 or 2 (IDH1/IDH2), vorasidenib is well tolerated and demonstrates antitumour activity, according to the results of a phase I study.

The phase I, dose-escalation study included 93 patients with mutant IDH1/2 (mIDH1/2) solid tumours, including 52 patients with glioma that had recurred or progressed following standard therapy. Vorasidenib was given orally, once daily, in 28-day cycles until progression or unacceptable toxicity.

Of the patients with glioma, 22 had nonenhancing and 30 had enhancing disease. The median age of the group was 42.5 years, and nearly all patients had WHO grade II (48.1 percent) or III (42.3 percent) tumours.

Vorasidenib showed a favourable safety profile at once-daily doses of <100 mg in the glioma group. Dose-limiting toxicities of elevated transaminases occurred at doses ≥100 mg and were reversible.

The protocol-defined objective response rate per Response Assessment in Neuro-Oncology criteria for LGG was 18 percent (one partial response, three minor responses) among patients with nonenhancing glioma.

The median progression-free survival was 36.8 months (95 percent confidence interval [CI], 11.2–40.8) in the subgroup of patients with nonenhancing glioma and 3.6 months (95 percent CI, 1.8–6.5) in the subgroup of those with enhancing glioma.

In an exploratory evaluation of tumour volumes in the nonenhancing glioma subgroup, multiple patients exhibited sustained tumour shrinkage.