Core Viewpoint - The recent clinical trial data presented by Keren Biotechnology at the 2025 European Society for Medical Oncology (ESMO) conference indicates that sac-TMT (TROP2 ADC) is the first drug to achieve both progression-free survival (PFS) and overall survival (OS) benefits in the second-line treatment of EGFR-mutant non-small cell lung cancer (NSCLC), addressing a significant treatment gap in this area [2][6]. Group 1: Clinical Trial Results - The OptiTROP-Lung04 study evaluated the efficacy and safety of sac-TMT compared to platinum-based doublet chemotherapy in patients with locally advanced or metastatic EGFR-mutant NSCLC [4]. - The study enrolled 376 patients, with a median follow-up of 18.9 months, showing a median PFS of 8.3 months for sac-TMT versus 4.3 months for chemotherapy, representing a 51% reduction in the risk of disease progression or death [4]. - The OS for sac-TMT was not reached (NR) compared to 17.4 months for chemotherapy, indicating a 40% reduction in the risk of death, with an objective response rate (ORR) of 60.6% versus 43.1% for chemotherapy [4][6]. Group 2: Safety Profile - The most common treatment-related adverse events (TRAEs) for both sac-TMT and chemotherapy were hematologic toxicities, with no reported cases of interstitial lung disease (ILD) or pneumonia in the sac-TMT group, suggesting a manageable safety profile [4][6]. Group 3: Future Directions - Following the promising results in second-line treatment, Keren Biotechnology has initiated a phase III clinical trial (SKB264-Ⅲ-15) to evaluate sac-TMT in combination with osimertinib compared to osimertinib alone in first-line treatment for patients with EGFR-mutant locally advanced or metastatic NSCLC [7]. - The significant clinical need for effective treatments in EGFR-mutant NSCLC has led to multiple investigational drugs targeting this indication, highlighting the competitive landscape in this therapeutic area [6][7].

Core Viewpoint - The breakthrough in overcoming EGFR-TKI resistance in non-small cell lung cancer (NSCLC) is a common goal for new therapies, with the recent clinical data from Kolonbo Tai's TROP2 ADC sac-TMT showing significant benefits in both progression-free survival (PFS) and overall survival (OS) for EGFR-mutant NSCLC patients in the second-line treatment setting [1][3]. Group 1: Clinical Study Results - The III phase clinical study (OptiTROP-Lung04) evaluated sac-TMT against platinum-based doublet chemotherapy in patients with locally advanced or metastatic EGFR-mutant NSCLC, enrolling 376 patients with a median follow-up of 18.9 months [3]. - The study reported a median PFS of 8.3 months for sac-TMT compared to 4.3 months for chemotherapy, representing a 51% reduction in the risk of disease progression or death [3]. - The OS for sac-TMT was not reached (NR) versus 17.4 months for chemotherapy, indicating a 40% reduction in the risk of death [3]. - The objective response rate (ORR) was 60.6% for sac-TMT compared to 43.1% for chemotherapy, with a median duration of response (mDoR) of 8.3 months versus 4.2 months [3]. Group 2: Safety Profile - The most common treatment-related adverse events (TRAEs) for sac-TMT and platinum-based chemotherapy were hematologic toxicities, with no reported cases of interstitial lung disease (ILD) or pneumonia in the sac-TMT group, indicating a manageable safety profile [4]. Group 3: Future Directions - The results from the study suggest that sac-TMT has achieved statistically significant and clinically meaningful improvements in both OS and PFS compared to chemotherapy, addressing the challenge of obtaining OS advantages after EGFR-TKI resistance [5]. - Kolonbo Tai plans to expand the use of sac-TMT into first-line treatment, with a new III phase clinical study (SKB264-III-15) initiated to evaluate sac-TMT in combination with osimertinib against osimertinib monotherapy in patients with EGFR-mutant NSCLC [7].