EGFR L858R

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.

For ALK mutations, the analysis showed that patients with ALK-positive tumors had distinct radiological features, including a higher occurrence in the lower lobes and fewer ground glass nodules compared to the WT group. The study concluded that specific radiological and pathological characteristics, along with EGFR and ALK mutation statuses, could be used to guide the treatment and diagnosis of lung adenocarcinoma.

Patients with advanced NSCLC and refractory MPE have a poorer prognosis after first-line targeted therapy than those with non-refractory MPE. More aggressive systemic and local treatment approaches may offer better survival benefits in these patients.

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

No significant differences were observed between epidermal growth factor receptor mutation subtypes. These findings are consistent with previous real-world studies and the placebo arm of the ADAURA trial, supporting the use of adjuvant osimertinib to reduce recurrence and improve long-term outcomes, while also emphasizing the need for improved perioperative risk assessment - including staging, histopathologic features, and molecular and genetic profiling - to guide personalized treatment.

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.

MTT assay showed that 6 and 9b were 4.5 and 2 times more potent than doxorubicin against MCF-7 cells, while 9a and 13b were 10 and 7.5 times more effective against MDA-MB-231 cells, respectively...Compound 13b exhibited comparable EGFRL858R inhibition to lapatinib and outperformed pictilisib against PI3Kα, PI3Kβ, and PI3Kδ. Compound 6 showed greater ARO inhibition than letrozole, while being slightly less potent than pictilisib against PI3Kα and PI3Kβ...Docking studies supported the in vitro enzymatic inhibition assays results. Thus, 9b and 13d are potent anti-breast cancer benzoxazoles with selective ARO and PI3kα inhibition activity, respectively, while 6, 9a, and 13b are multi-target inhibitors exhibiting other anticancer synergistic mechanisms.

P2, N=150, Active, not recruiting, Myung-Ju Ahn | Trial completion date: Jul 2025 --> Dec 2026 | Trial primary completion date: Mar 2025 --> Mar 2026

Aumolertinib plus anlotinib was effective and well-tolerated as first-line therapy in EGFR-mutant NSCLC patients with BMs. Trial Registration: ClinicalTrials.gov(identifier NCT04978753, registered July 20, 2021).

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.