Servier's Dual IDH1/2 Inhibitor Vorasidenib Shows Promising Efficacy in Glioma with Median PFS of 3.1 Years
Jun 21, 2021 03:08
CST Updated
03:08
Servier
International Pharmaceutical Manufacturers
Glioma (Image source: hmcisrael.com)
June 20, 2021 /BioonBIOON/ -- Servier recently announced that the results of a Phase 1 dose-escalation clinical trial (NCT02481154) evaluating vorasidenib as monotherapy for advanced solid tumors with isocitrate dehydrogenase (IDH) mutations (including low-grade gliomas, LGG) have been published in the prestigious international oncology journal *Clinical Cancer Research*.Vorasidenib is an investigational, oral, selective, brain-penetrant dual inhibitor targeting mutant IDH1 and IDH2 enzymes.
In the first-in-human study (NCT02481154), a total of 93 patients with IDH1/2-mutant advanced solid tumors were enrolled, including 52 patients with glioma. In the study, vorasidenib was administered orally once daily in 28-day cycles until disease progression or unacceptable toxicity.
The results showed that vorasidenib demonstrated a favorable safety profile at once-daily doses <100 mg and exhibited preliminary clinical activity in patients with recurrent or progressive IDH1/2-mutant low-grade glioma. Study data indicate that,In patients with non-enhancing low-grade glioma, the median progression-free survival (PFS) was 36.8 months (3.1 years).[95% confidence interval (CI): 11.2-40.8 months]. According to the Response Assessment in Neuro-Oncology for low-grade gliomas (RANO-LGG) criteria,In patients with non-enhancing low-grade glioma, the protocol-defined objective response rate (ORR) was 18%.(1 case of partial response, 3 cases of minor response). Exploratory assessment of tumor volume showed,Of Multiple Patients With Non-Enhancing Low-Grade GliomasTumorVolume continues to decrease.
Mutations in the metabolic enzymes IDH1/2 occur in approximately 80% of patients with low-grade glioma (LGG).The standard treatment for LGG comprises tumor resection, followed by radiotherapy and/or chemotherapy as indicated. This therapeutic approach is not curative, and current therapies are associated with short- and long-term toxicities. Most patients experience disease recurrence and progression to higher...TumorGrade. In this study, vorasidenib demonstrated a favorable safety profile. Dose-limiting toxicity of transaminase elevation occurred at ≥100 mg and was reversible.
Dr. Tim Cloughesy, an investigator for the study and a neurologist at the David Geffen School of Medicine at UCLA, stated: “Given the toxicities associated with chemotherapy and radiation therapy, there remains a significant unmet need for treatment options that can improve outcomes for patients with IDH-mutant low-grade glioma. These early results reinforce the potential therapeutic benefit of vorasidenib in IDH-mutant low-grade glioma.”
Chemical structure of vorasidenib (Image source: medchemexpress.com)
Currently, Servier is conducting the Phase 3 INDIGO registration study (NCT04164901) to evaluate the activity of vorasidenib in early-stage disease as a potential treatment for patients with residual or recurrent grade 2 low-grade glioma. Delaying the need for more aggressive treatment at an early stage may provide meaningful benefits to patients.
Gliomas exhibit varying degrees of aggressiveness, ranging from slow-growing (low-grade gliomas) to rapidly progressive (high-grade gliomas, such as glioblastoma multiforme). Tumor enhancement is an imaging characteristic evaluated using magnetic resonance imaging (MRI), and the enhancing typeTumorMore likely to progress to a higher grade.
Common symptoms of glioma include seizures, memory impairment, sensory disturbances, and neurological deficits. Regardless of treatment, the long-term prognosis is poor; most patients with low-grade gliomas will experience disease recurrence that progresses over time. In the United States and the European Union, approximately 11,000 patients are diagnosed with low-grade glioma annually, with approximately 80% of patients harboring an IDH mutation. (Bioon.com)