Orbus Therapeutics Announces Publication of Phase 3 STELLAR Clinical Study Results Showing Clinically Meaningful Improvements in Rare Brain Tumor in Journal of Clinical Oncology (JCO)

– Eflornithine and lomustine combination doubled progression free survival (PFS) and improved overall survival (OS) in patients with recurrent Grade 3 astrocytoma –

PALO ALTO, Calif., Dec. 02, 2025 (GLOBE NEWSWIRE) -- Orbus Therapeutics, Inc., a private pharmaceutical company, today announced the publication of the Phase 3 STELLAR clinical study results demonstrating that the combination of eflornithine and lomustine achieved clinically meaningful improvements in OS and PFS compared to lomustine alone in patients with recurrent IDH mutant, grade 3 astrocytoma. Based on current World Health Organization (WHO) CNS5 tumor classification, this molecularly defined population represents all diagnosed patients with grade 3 astrocytoma. No benefits were observed in patients with grade 4 disease or the primary endpoint in the ITT population. The results were published in the ASCO Journal of Clinical Oncology.

Eflornithine is a unique inhibitor of ornithine decarboxylase (ODC), an enzyme that is integral to cellular division and proliferation and that can become upregulated in gliomas fueling rapid growth. By inhibiting ODC, eflornithine disrupts this process, thereby slowing cell growth and tumor progression.

“Grade 3 astrocytoma is an aggressive malignant glioma that is challenging to treat despite radiation and chemotherapy. When it recurs, as it does in most cases, patients are faced with limited treatment options and a very poor prognosis,” said Howard Colman, MD, PhD, FAAN, the Jon M. Huntsman Presidential Chair in Neuro-Oncology at the Huntsman Cancer Institute at the University of Utah. “The positive results in patients with recurrent IDH mutant grade 3 astrocytoma in the STELLAR study represent a true breakthrough as the first treatment to show this magnitude of benefit compared to the standard of care in this fatal tumor type, and a major step forward for patients.”

“The publication in JCO underscores the strength of the data, which we hope will provide a meaningful advancement for patients facing this devastating disease who have had no new chemotherapy options in over two decades,” said Jason Levin, President and Chief Executive Officer of Orbus. “To our knowledge, this magnitude of improvement demonstrated with the eflornithine/lomustine combination compared to standard of care has not been seen in this patient population. We look forward to working collaboratively with the FDA and other regulatory authorities on next steps to identify a path to making eflornithine available as a potential new therapy for these patients.”

The STELLAR study (NCT02796261) was designed to evaluate the efficacy and safety of eflornithine in combination with lomustine compared to lomustine alone in patients with anaplastic astrocytoma that recurs after surgery, irradiation and adjuvant temozolomide chemotherapy. The study enrolled a total of 343 patients who were stratified by key characteristics, including IDH mutation status. In the overall intent-to-treat (ITT) population, which was defined per the previous WHO CNS4 tumor classification (2016) and included patients currently defined as having both grade 4 astrocytoma and glioblastoma and grade 3 astrocytoma, there was no overall difference in the primary endpoint of OS (HR = 0.95) or in PFS between arms. Of the total population of patients enrolled, however, 57% of the patients (n=196) had grade 3 IDH mutant astrocytoma tumors, as defined by the subsequent, and currently used, WHO CNS5 tumor reclassification (2021).

The JCO publication describes a prospective analysis (prior to unblinding) performed in the intended target tumor population, patients with IDH mutant grade 3 (without CDKN2A/B homozygous deletion) astrocytoma per the WHO CNS5 tumor reclassification (2021):

• In the 196 patients with recurrent grade 3 IDH mutant astrocytoma subset, clinically meaningful improvements in both OS and PFS were observed.
• Median OS in the eflornithine + lomustine arm was 34.9 months compared to 23.5 months in the lomustine alone arm with HR = 0.64 (log rank p = 0.01).
• PFS showed a correlating benefit with median PFS of 15.8 months in the eflornithine + lomustine arm and 7.2 months in the lomustine alone arm with HR = 0.57 (log rank p = 0.01).
• The combination of eflornithine + lomustine was generally well-tolerated. The known side effect profile of eflornithine combined with lomustine was consistent with data from earlier studies and no new safety signals were identified. The most common Grade 3+ treatment emergent adverse events of relevance were related to myelosuppression and hearing impairment. Similarly, the proportion of patients with Grade 3+ hematology parameters and those with Grade 3 + clinical chemistry parameters were as expected.

The JCO publication titled “STELLAR: Phase 3, randomized, open-label study of eflornithine plus lomustine versus lomustine alone in patients with recurrent grade 3 astrocytoma” can be found on the JCO website.

About WHO Tumor Classification

The WHO tumor classification system is a globally recognized framework used to categorize tumors - especially cancers - based on histology, genetic features, and their grade. This system is published and updated by the WHO to ensure that diagnoses are standardized across the world and to help guide treatment decisions. For tumors of the central nervous system, based on improved understanding of biomarkers, the 2021 WHO update reclassified gliomas to incorporate a fully-integrated and molecular-based classification for diagnosis, defined by IDH mutation status and grade. The STELLAR study began prior to 2021 and, consequently, had two subsets of previously classified and enrolled “Grade 3” patients change designation to Grade 4 under the updated 2021 WHO CNS tumor reclassification.

About Eflornithine

Eflornithine is a novel cytostatic agent that irreversibly inhibits ornithine decarboxylase, a key enzyme in mammalian polyamine biosynthesis that is upregulated in certain types of cancer.

Eflornithine has been granted Orphan Drug Designation and Breakthrough Therapy Designation for the treatment of patients with anaplastic glioma by the U.S. Food and Drug Administration (FDA) and has also been granted Orphan Medicinal Product status for the treatment of glioma by the Committee for Medicinal Products for Human Use (CHMP) at the European Medicines Agency (EMA).

About Orbus Therapeutics

Orbus Therapeutics Inc. is a late-stage, private biopharmaceutical company that is dedicated to developing products that treat rare diseases for which there are few, if any, effective therapies. The Company’s lead product candidate, eflornithine, has completed one Phase 3 clinical study in patients with recurrent anaplastic astrocytoma, a rare form of central nervous system cancer. For more information, please visit the Company's website at http://www.orbustherapeutics.com.

Contact Information:
Jason Levin
jason.levin@orbustherapeutics.com

Media:
Kelli Perkins
kelli@redhousecomms.com

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