Orbus Therapeutics' lead therapy, eflornithine, in combination with lomustine, failed to achieve the primary endpoint in the Phase III STELLAR trial for patients with recurrent isocitrate dehydrogenase (IDH) mutant astrocytoma. While the study did not meet its primary efficacy endpoint of overall survival (OS), the combination therapy demonstrated clinically meaningful improvements in OS and progression-free survival (PFS) compared to lomustine monotherapy.
The Phase III trial enrolled 343 patients with recurrent IDH mutant astrocytoma, a brain cancer that has recurred following radiation and adjuvant temozolomide chemotherapy. Of these, 194 patients had grade 3 IDH mutant astrocytoma. The combination therapy arm achieved a median OS of 34.9 months compared to 23.5 months in the lomustine monotherapy group. The median PFS was 15.8 months in the combination group, compared to 7.2 months in the lomustine monotherapy arm.
Safety and Tolerability
Orbus reported that the combination therapy was well-tolerated, and no unexpected safety signals were observed during the trial. The most common grade 3 or higher adverse events were associated with myelosuppression and hearing impairment.
Mechanism of Action and Prior Designations
Eflornithine functions by irreversibly blocking ornithine decarboxylase (ODC), a crucial enzyme involved in cell division and proliferation, which is associated with various types of cancer. The US Food and Drug Administration (FDA) had previously granted eflornithine orphan drug and breakthrough therapy designations for the treatment of anaplastic glioma, a term encompassing IDH mutant astrocytoma, oligodendroglioma, and glioblastoma.
Eflornithine in Other Indications
Last year, the FDA approved eflornithine for reducing the risk of relapse in adult and pediatric patients with high-risk neuroblastoma (HRNB), where it is marketed by US WorldMeds as Iwilfin. In January, Orbus also signed an exclusive license agreement with Michigan State University (MSU) and Helen DeVos Children’s Hospital (HDVCH) for using eflornithine in the treatment of Bachmann-Bupp Syndrome (BABS), a rare genetic pediatric neurodevelopmental disorder.
The results from the STELLAR trial were presented at the 29th Annual Meeting and Education Day of the Society for Neuro-Oncology in Houston, Texas.
