Recently, the highly anticipated 2025 World Conference on Lung Cancer (WCLC) was held in Barcelona, Spain. As the world's largest and most influential academic conference in the lung cancer field, it primarily focuses on lung cancer basic research, clinical diagnostic and therapeutic advances, and innovative therapy exploration, serving as a core platform for driving global innovation in lung cancer diagnosis and treatment technologies. The oral presentation session only accepts studies with "high scientific innovation, clinical relevance, and breakthrough data," committed to providing higher-level evidence-based medical evidence for existing key clinical issues and revealing future directions in lung cancer treatment.
TYK MEDICINES-B (02410)'s independently developed innovative drug alotinib tablets (TY-9591) for EGFR-mutated advanced non-small cell lung cancer (NSCLC) achieved selection for the WCLC 2025 Mini Oral presentation (presentation number MA08.06) with results from its pivotal Phase II clinical trial (NCT05948813). The presentation was delivered by principal investigator Professor Shi Yuankai from the Cancer Hospital of the Chinese Academy of Medical Sciences.
The ESAONA pivotal registration trial selected for Mini Oral presentation is an open-label, multicenter, randomized controlled Phase II clinical trial focusing on NSCLC patients with EGFR mutations (L858R or 19Del) and brain metastases. The study aims to compare the first-line efficacy and safety of alotinib (160mg, once daily) versus osimertinib (80mg, once daily) in treatment-naïve NSCLC patients with EGFR-sensitive mutations and brain metastases.
As of February 28, 2025, the study enrolled 257 patients with EGFR-mutated NSCLC with brain metastases. In terms of efficacy, interim analysis based on data from 224 patients showed:
According to RECIST criteria assessment, the blinded independent central review (BICR) intracranial objective response rate (iORR) reached 92.8% (95% CI: 86.3-96.8%) in the alotinib group, compared to 76.1% (95% CI 67.2-83.6%) in the osimertinib group, P=0.0006. Investigator-assessed iORR was 91.0% (95% CI 84.1-95.6%) in the alotinib group versus 75.2% (95% CI 66.2-82.9%) in the osimertinib group, P=0.002.
According to RANO-BM assessment criteria, investigator-assessed confirmed iORR was 90.1% (95% CI: 83.0%-94.9%) and 74.3% (95% CI: 65.3%-82.1%) for the alotinib and osimertinib groups respectively, P=0.0023. Systemic objective response rate (ORR) showed a favorable trend (84.7% vs. 75.2%), while intracranial progression-free survival (iPFS), systemic, and overall survival (OS) data remain immature.
Regarding safety, the incidence of grade ≥3 treatment-related adverse events was 31.5% in the alotinib group and 15.0% in the osimertinib group. The most common grade ≥3 adverse reactions in the alotinib group included elevated creatine phosphokinase, QTcf interval prolongation, neutropenia, and leukopenia. The incidence of interstitial lung disease (ILD) was 6.3%, and QTcf prolongation was 4.5%, both within manageable and monitorable ranges.
In this context, currently no third-generation EGFR-TKIs have been approved globally for NSCLC brain metastases indication. As a third-generation EGFR-TKI candidate drug applicable to non-small cell lung cancer brain metastases, alotinib's pivotal Phase II clinical results challenging osimertinib being selected for oral presentation at this WCLC conference marks recognition of its efficacy and safety data by the international authoritative academic community, demonstrating significant clinical translation potential. This is expected to address the urgent unmet clinical medical needs of EGFR-mutated NSCLC patients with brain metastases.
Under the current domestic policy environment that comprehensively supports innovative drug development, alotinib is expected to leverage its differentiated innovation capabilities to establish a solid foundation for future product commercialization prospects.