According to a phase 2 study, asandeutertinib showed efficacy and tolerable safety among patients with locally advanced or metastatic EGFR-mutant non-small cell lung cancer (NSCLC) and brain metastases.

These data will be first presented by Ligang Xing, MD, Peking Union Medical College, at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, Illinois.

The deuterated osimertinib derivative, asandeutertinib is a novel central nervous system-active third generation EGFR tyrosine kinase inhibitor. It is suggested that asandeutertinib can potently and selectively inhibit EGFR-sensitizing mutations and T790M resistance mutations. In a previous phase 1 study, asandeutertinib showed clinical efficacy among patients with NSCLC with EGFR mutations.

This phase 2 study enrolled 29 patients with locally advanced or metastatic EGFR-mutant NSCLC and brain metastases. Patients received 160 mg asandeutertinib once daily. There were 27 patients with EGFR-sensitizing mutations who had not received any prior EGFR tyrosine kinase inhibitors, with 2 patients with EGFR T790M resistance mutations had previously received a first- or second-generation EGFR tyrosine kinase inhibition. The primary end points were intracranial objective response rate (ORR) and extracranial ORR, both assessed by investigators.

With a median follow-up duration of 16.4 months, the confirmed intracranial ORR was 93.1%. The confirmed intracranial ORR among those who had not received prior EGFR inhibition was 92.6%. The 2 patients who had received prior EGFR inhibition achieved intracranial partial responses. The median intracranial duration of response and intracranial progression-free survival were not reached. At 12 months, the rate of intracranial duration of response was 82.8% and of intracranial progression-free survival was 96.6%.

The incidence of treatment-related adverse events was 93.1%. The most common treatment-related adverse events, experienced by ≥ 10% of patients, included decreased white blood cell count, decreased absolute neutrophil count, decreased platelet count, elevated serum creatine phosphokinase, and diarrhea. The rate of grade 3 treatment-related adverse events was 27.6%, and there were no grade 4 or 5 events reported. There were 5 patients who experienced 6 serious adverse events, of which the events of 2 patients were study drug-related. There were no incidents of interstitial lung disease, cardiomyopathy, or keratitis.

Dr Xiang et al concluded, “asandeutertinib is highly effective and well-tolerated in locally advanced or metastatic EGFR [mutated] NSCLC patients with [brain metastases].”

Source:

Xing P-Y, Zing L, Cheng Y, et al. A phase II study of asandeutertinib (TY-9591) in advanced NSCLC patients with EGFR-positive mutations and brain metastases. Presented at 2025 ASCO Annual Meeting. May 30-June 3, 2025; Chicago, IL. Abstract 2004.