Tagrisso (osimertinib)

P3, N=744, Active, not recruiting, AstraZeneca | Recruiting --> Active, not recruiting | Trial completion date: May 2028 --> Sep 2028 | Trial primary completion date: Jun 2026 --> Sep 2026

These findings suggest that osimertinib causes reversible cardiac dysfunction by disrupting MYL2 phosphorylation via GATA4 dephosphorylation-mediated suppression of MYLK3 and highlight the potential of myosin activation as a preventive or rescue strategy for osimertinib cardiotoxicity.

Treatment with fasudil, a Rho kinase inhibitor, effectively blocked mitochondrial transfer and restored sensitivity to the EGFR-TKI osimertinib in vivo. Together, this work reveals targetable stromal-tumor crosstalk that sustains DTP populations, proposing a combination therapy for overcoming EGFR-TKI resistance.

P2, N=120, Not yet recruiting, CSPC Megalith Biopharmaceutical Co.,Ltd.

A plasma sample serves as a supplement for identifying GPS when a tissue sample is unavailable. Moreover, the integration of FISH, NGS, and ddPCR provided a comprehensive assessment of MET amplification.

P2, N=300, Recruiting, Shanghai Hengrui Pharmaceutical Co., Ltd. | Not yet recruiting --> Recruiting

To model acquired resistance, PC-9 cells were exposed to vinorelbine or paclitaxel for 18 weeks-approximating the clinical duration of four adjuvant chemotherapy cycles-and subsequent drug sensitivity and signaling pathway alterations were assessed using cell viability assays, RNA sequencing, and immunoblotting. These findings suggest that CaMKII plays a critical role in EGFR-TKI resistance. This study underscores the importance of optimizing the timing of EGFR-TKI administration in the therapeutic sequence for EGFR-mutated NSCLC.

P1/2, N=48, Recruiting, Wayshine Biopharm, Inc. | Not yet recruiting --> Recruiting

Collectively, these results indicated that Casticin suppresses and sensitizes non-small-cell lung cancer cells to EGFR-TKIs. Casticin may serve as a sensitizing agent by targeting SMYD2 to improve the efficacy of EGFR-TKIs.

Our results further reveal that the MUC1-C-driven STAT1 inflammatory response promotes resistance of patient-derived (i) EGFR mutant NSCLC cells with MET amplification to the combination of osimertinib+MET TKIs, and (ii) EGFR(T790M/C797S) NSCLC cells to the 4th generation EGFR TKI TQB3804. Of clinical significance, we report that NSCLC cells dependent on MUC1-C for TKI resistance are druggable with an antibody-drug conjugate (M1C ADC) in vitro and in a PDX tumor model. These findings demonstrate that MUC1-C (i) is essential for TKI resistance of NSCLC cells by driving an inflammatory memory response and (ii) is a target for M1C ADC treatment of TKI-refractory NSCLCs.

Both almonertinib and osimertinib demonstrated good efficacy in patients with brain metastases, and PD-L1 expression was not associated with the prognosis of EGFR L858R mutant NSCLC. Finally, no significant difference between osimertinib and almonertinib for the treatment of patients with EGFR L858R mutations was observed. Both options remain viable for these patients.

Savolitinib plus osimertinib demonstrated numerically higher clinical activity versus savolitinib plus placebo in all patients and patients with higher MET biomarker cutoffs.