Efficacy and safety of asandeutertinib versus osimertinib as first-line treatment in EGFR-mutated NSCLC patients with brain metastases: Interim analysis of an open-label, multicenter, randomized, pivotal phase II study (ESAONA).

Abstract

LBA2007 Background: Asandeutertinib (TY-9591), a novel EGFR-TKI candidate, demonstrated outstanding efficacy and manageable safety in its Phase I and Phase II studies. The ESAONA study was designed to compare the efficacy and safety between asandeutertinib and osimertinib in EGFR-mutated non-small cell lung cancer (NSCLC) with brain metastases (BM). Methods: In the ESAONA study, treatment-naïve NSCLC pts with EGFR-sensitizing mutations and stable BM have been enrolled and randomized 1:1 to receive either asandeutertinib (160 mg orally, QD) or osimertinib (80 mg orally, QD). Randomization was stratified according to the number of intracranial lesions (>3 or ≤3) and EGFR mutation type (L858R or 19Del). The primary endpoints were intracranial objective response rate (iORR) and intracranial progression-free survival (iPFS), assessed by the blinded independent central review (BICR) per RECIST version 1.1. Results: From August 14, 2023 to December 15, 2025, 224 eligible pts were enrolled and randomized to asandeutertinib (n=111) or osimertinib (n=113), with a median follow-up of 18.86 months (mo) and 19.12 mo, respectively. Baseline characteristics were well balanced. Results showed that asandeutertinib significantly improved the BICR-assessed iORR compared with osimertinib (95.5% [95%CI, 89.8%-98.5%] vs. 79.6% [95%CI, 71.0%-86.6%]; p=0.0004). INV-assessed iORR was 92.8% [95%CI, 86.3%–96.8%] in asandeutertinib and 77.9% [95%CI, 69.1%-85.1%] in osimertinib (p=0.0019). INV-assessed iORR per RANO-BM showed a consistent trend (91.9%, [95%CI, 85.2%-96.2%] vs. 77.9%, [95%CI, 69.1%-85.1%], p=0.0039). BICR-assessed Median iPFS (miPFS) was not reached [95%CI, 22.24–NA] in asandeutertinib and 17.51 mo [95%CI, 15.18–NA] in osimertinib (HR 0.46 [95%CI, 0.28-0.76]; p=0.0020). The trend in miPFS was consistent across subgroups. INV-assessed miPFS was not reached [95%CI, 21.45–NA] in asandeutertinib and 17.51 mo [95%CI, 15.38–21.36] in osimertinib (HR 0.56 [95%CI, 0.36-0.89]; p=0.0122). INV-assessed miPFS per RANO-BM also favored asandeutertinib (22.64 vs. 17.51 mo; HR 0.60 [95%CI, 0.39-0.94]; p=0.0232). BICR-assessed mPFS was not reached [95%CI, 17.22–NA] with asandeutertinib vs 17.22 mo [95%CI, 15.18–19.55] with osimertinib (HR 0.64 [95%CI, 0.41-1.00]; p=0.0473). Systemic efficacy was numerically favored asandeutertinib, and OS remained immature. Treatment-related adverse events (TRAEs) was 99.1% in asandeutertinib and 95.6% in osimertinib. Treatment-related serious adverse events was 10.8% in asandeutertinib and 7.1% in osimertinib. Conclusions: Asandeutertinib significantly improved iORR and iPFS compared to osimertinib, with manageable safety profile, supporting its potential as a new first-line treatment for EGFR-mutated NSCLC pts with BM. Clinical trial information: NCT05948813 .