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The investigational epidermal growth factor receptor (EGFR) inhibitor asandeutertinib was associated with better intracranial objective response rate (iORR) and intracranial progression-free survival (iPFS) than osimertinib as first-line therapy for patients with EGFR-mutated non-small cell lung cancer (NSCLC) and brain metastases, interim results of a phase 2 trial showed.
The asandeutertinib group had an intracranial response rate of 95.5% vs 79.6% for the osimertinib group, while the risk for intracranial progression or death was 54% lower in the investigational group.
Lead study author Yuankai Shi, MD, PhD, said this is the first EGFR inhibitor to demonstrate superiority over osimertinib for both iORR and iPFS in this setting.
These results support asandeutertinib as a potential first-line treatment for EGFR-mutated NSCLC with brain metastases, added Shi, who is of the National Cancer Center and Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
The study, being conducted in China, was presented in an oral abstract session at the American Society of Clinical Oncology (ASCO) 2026 in Chicago.
A High-Risk Population
Although brain metastases are common and associated with worse outcomes in EGFR-mutated NSCLC, no EGFR inhibitor has been specifically approved for this indication, Shi said. Osimertinib, a brain-penetrant third-generation EGFR inhibitor, is the current first-line standard, but intracranial progression remains common.
Asandeutertinib, also known as TY-9591, is a deuterated third-generation EGFR TKI that has shown activity and manageable safety in earlier phase 1 and phase 2 studies.
The ESAONA trial continued this work by comparing asandeutertinib with osimertinib among patients with NSCLC and brain metastases.
Trial Design
ESAONA enrolled 224 treatment-naive patients with EGFR-sensitizing mutations and stable brain metastases.
Participants were randomized in a 1:1 ratio to receive asandeutertinib 160 mg (n = 111) or osimertinib 80 mg (n = 113) once daily. Randomization was stratified by the number of intracranial lesions and by mutation type (L858R or exon 19 deletion).
The primary endpoints were iORR and iPFS, assessed by blinded independent central review per RECIST version 1.1.
Better Intracranial Control
After a median follow-up of approximately 19 months in each group, central review showed an iORR significantly higher with asandeutertinib than with osimertinib (95.5% vs 79.6%; P = .0004), and investigator-assessed rates showed a consistent advantage (92.8% vs 77.9%). Intracranial duration of response also favored asandeutertinib.
Median iPFS was not reached with asandeutertinib vs 17.5 months with osimertinib (hazard ratio, 0.46; P = .0020). This benefit was consistent across subgroups and assessment methods.
Systemic PFS numerically favored asandeutertinib, while overall survival data remained immature.
Treatment-related adverse events occurred in 99.1% of asandeutertinib-treated patients vs 95.6% of osimertinib-treated patients, with serious treatment-related events in 10.8% and 7.1%, respectively. Most events were grade 1 or 2 in both groups.
On the basis of these interim results, a conditional new drug application for asandeutertinib has been accepted by China’s National Medical Products Administration and granted priority review, Shi noted.
Audience Questions
Priya Kumthekar, MD, a neuro-oncologist at Northwestern University Feinberg School of Medicine in Chicago, who moderated the session, asked about the extracranial (ie, systemic) response rate.
The extracranial response rate was also significantly higher in the asandeutertinib group, Shi replied, although he did not share exact figures. When Kumthekar asked if the extracranial response rate was as high as the intracranial response rate, Shi said the two rates were “almost the same.”
Jay-Jiguang Zhu, MD, PhD, a neuro-oncologist at UTHealth Houston, Houston, asked about rates of leptomeningeal disease in the two groups.
Shi said the trial enrolled patients with brain metastases but not leptomeningeal disease.
Asked whether any cases of leptomeningeal disease had developed during the trial, Shi said none had emerged so far, with follow-up ongoing.
The study was funded by TYK Medicines Inc., the developer of asandeutertinib. Shi and his co-authors reported having no relationships. Kumthekar disclosed having relationships with GlaxoSmithKline, Jazz Pharmaceuticals, Novocure, and others.
