EGFR T790M

This study underscores the clinical importance of the rare germline EGFR T790M mutation in lung cancer. Detecting carriers with a family history may allow earlier diagnosis and inform targeted prevention, supporting more precise screening for high-risk individuals.

Furthermore, we validated the specificity of our approach by successfully detecting various mutations, including KRAS G12C, KRAS G12D, EGFR T790M and TP53 R273H, in simulated clinical samples. These findings highlight a reliable method for precise ctDNA detection, offering high specificity, selectivity, and accuracy, thus paving the way for potential cancer diagnostic application.

In colon and lung tumor models, NanoTACs suppressed tumor growth by 88.3%, achieved 95% degradation of wild-type and 80% of mutant EGFR, and induced extensive apoptosis without systemic toxicity. These findings established NanoTACs as a promising EGFR-targeted platform to overcome drug resistance to mAbs and TKIs by enabling effective degradation of wild-type and mutant EGFR in heterogeneous cancers.

Despite initial responses to first-line firmonertinib-based combination therapy, progression-free survival (PFS) 13 months, the patient developed sequential resistance to subsequent regimens, including liver/brain metastases and treatment-related toxicities. After fourth-line therapy failure and severe intolerance to albumin-bound paclitaxel and bevacizumab, two cycles of ivonescimab-a first-in-class programmed cell death protein receptor-1 (PD-1)/vascular endothelial growth factor-A (VEGF-A) bispecific antibody-induced significant regression of pulmonary target lesions (PR), sustained over six cycles with minimal toxicity...While the rapid PR and favorable safety profile are promising, longer follow-up is required to assess durability and survival benefits. These findings underscore the need for further investigation of bispecific antibodies in precision oncology paradigms for multi-refractory EGFR-driven NSCLC.

P1/2, N=200, Active, not recruiting, Black Diamond Therapeutics, Inc. | Trial primary completion date: Jul 2025 --> Nov 2025

P1, N=24, Recruiting, Ohio State University Comprehensive Cancer Center | Trial primary completion date: Jul 2025 --> Jul 2026

Compound 5k (IC50 = 0.99 ± 0.45 μM) and 5i (IC50 = 1.15 ± 0.14 μM) demonstrated markedly higher potency against MDA-MB-231 cells compared to cisplatin (IC50 = 34.36 ± 0.16 μM), whereas 5e was found active against A549 cells (IC50 = 1.41 ± 1.13 μM)...In silico ADMET profiling confirmed favorable drug-likeness and safety attributes. Together, these findings support the discovery of this novel class of covalent pyrrolo[2,3-d] pyrimidine cinnamamides as promising and safer lead candidates for anticancer therapy, particularly against triple-negative breast cancer.

This study demonstrates that EGFR-targeted therapy, when used in a first-line setting, significantly improves OS and PFS in this population. Further research is warranted to optimise treatment strategies, particularly in resource-limited settings.

In participants with atypical EGFR-mutated advanced NSCLC, amivantamab-lazertinib demonstrated clinically meaningful antitumor activity with no new safety signals.

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.

Kaplan-Meier and Cox regression analyses revealed no significant survival difference between hereditary and somatic mutation groups (median OS 24.9 vs. 24.0 months; log-rank p = 0.69; HR = 1.19; 95% CI, 0.52-2.73). These findings indicate that germline EGFR T790M represents a measurable hereditary variant within the South Caucasus population and emphasize the need to integrate germline testing into diagnostic workflows and familial risk assessment strategies for EGFR-driven NSCLC.

Patients received RAM (10 mg/kg every 2 wk) plus GEF (250 mg once daily) until disease progression (period 1); patients with disease progression who acquired a T790M mutation received RAM plus osimertinib (80 mg once daily) (period 2). Treatment-emergent T790M rate post progression was 81.3%. RELAY+ revealed a favorable benefit-risk profile for RAM plus GEF in East Asian patients with untreated EGFR-mutated metastatic NSCLC, supporting RAM plus GEF as an alternative first-line treatment option, particularly in those with an L858R mutation.