Orbus Therapeutics has announced positive results from its Phase 3 STELLAR trial, demonstrating that the combination of eflornithine and lomustine provides a clinically meaningful improvement in overall survival (OS) and progression-free survival (PFS) for patients with recurrent grade 3 IDH mutant astrocytoma. These patients had progressed following irradiation and adjuvant temozolomide treatment. The data were presented at the Society for Neuro-Oncology Annual Meeting.
The STELLAR study (NCT02796261) enrolled 343 patients, including a significant subset (n=194) with grade 3 IDH mutant astrocytoma, defined by WHO criteria. These patients were treated across 105 clinical trial centers in North America and Europe. The primary endpoint, OS in the intention-to-treat population, did not reach statistical significance (HR = 0.94). However, the pre-specified subgroup analysis revealed compelling benefits in the IDH mutant cohort.
Key Findings in IDH Mutant Astrocytoma
In the 194 patients with recurrent grade 3 IDH mutant astrocytoma, the combination of eflornithine and lomustine demonstrated a significant increase in median overall survival (OS) to 34.9 months, compared to 23.5 months with lomustine alone (HR = 0.64, log rank p = 0.016). Progression-free survival (PFS) also improved, with a median PFS of 15.8 months in the combination arm versus 7.2 months in the lomustine arm (HR = 0.58, log rank p = 0.015).
Safety and Tolerability
The combination therapy was generally well-tolerated. The observed side effect profile of eflornithine combined with lomustine was consistent with prior data, with no unexpected safety signals. The most common Grade 3+ treatment-emergent adverse events were related to myelosuppression and hearing impairment. The rates of Grade 3+ hematological and clinical chemistry abnormalities were as expected.
Expert Commentary
"The subset results for the patients with recurrent grade 3 astrocytoma in the STELLAR study represent the first positive outcome to show significant increases in overall survival and progression free survival in a very difficult-to-treat form of malignant glioma," said Howard Colman, MD, PhD, FAAN, from the Huntsman Cancer Institute at the University of Utah. "These findings from the STELLAR study are very impressive and provide caregivers and patients with hope for a new treatment option for this fatal disease."
About Eflornithine
Eflornithine is a cytostatic agent that inhibits ornithine decarboxylase, an enzyme involved in polyamine biosynthesis, which is often upregulated in cancer. The FDA has granted eflornithine Orphan Drug Designation and Breakthrough Therapy Designation for anaplastic glioma. The EMA has also granted Orphan Medicinal Product status for glioma.
