EGFR L858R

The Agena iPlex HS Lung Panel on the MassARRAY System is highly tolerant of poor quantity and quality DNA, recovering and delivering accurate results on samples that would otherwise fail NGS-based analysis.

P=N/A, N=40, Not yet recruiting, The Second Affiliated Hospital of Army Medical University; The Second Affiliated Hospital of Army Medical University

P2, N=180, Recruiting, Sun Yat-sen University Cancer Center; Sun Yat-sen University Cancer Center

P2, N=30, Not yet recruiting, Jining Medical University Affiliated Hospital; Jining Medical University Affiliated Hospital

P2, N=25, Recruiting, Cancer Hospital Affiliated of Shandong First Medical University; Cancer Hospital Affiliated of Shandong First Medical University

P3, N=192, Active, not recruiting, Jiangsu Hansoh Pharmaceutical Co., Ltd. | Trial primary completion date: Jan 2026 --> Jul 2024

P2, N=187, Active, not recruiting, AstraZeneca | Recruiting --> Active, not recruiting

The additional hydrogen bonds also influence the binding affinity of the EGFR kinase domain by altering the secondary structure and flexibility of the amino acid residues in the domain. Our work highlights how the two reported mutations may alter both residue-residue and residue-solvent hydrogen bonds, affecting protein binding properties, which could be helpful for future drug discovery.

Under the premise of not exacerbating adverse effects, neoadjuvant immunochemotherapy achieved superior rates of MPR and pCR, with long-term survival comparable to targeted therapy.

P2, N=117, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Dec 2024 --> Jun 2025 | Trial primary completion date: Dec 2024 --> Jun 2025

P=N/A, N=187, Enrolling by invitation, Pfizer | N=1200 --> 187

P3, N=586, Active, not recruiting, Daiichi Sankyo | Trial primary completion date: Aug 2024 --> May 2024

The genomic landscape varies significantly among patients with LUAD, which should be considered when making personalized treatment decisions. This information could provide insights into molecular changes and their effects on clinical treatment in diverse patients with LUAD harboring sensitizing EGFR mutations.

These effects are associated with binding of 1,4,5,6-tetrahydroxy-7,8-diprenylxanthone to EGFR resulting in the suppression of extracellular signal-regulated kinase (Erk) phosphorylation. In conclusion, our results suggest that 1,4,5,6-tetrahydroxy-7,8-diprenylxanthone may be a potential novel candidate for further investigation and treatment of NSCLC with the triple-mutant EGFR.

P2, N=40, Active, not recruiting, British Columbia Cancer Agency | Recruiting --> Active, not recruiting | N=76 --> 40

P2, N=160, Active, not recruiting, Xiuning Le | Trial completion date: Oct 2024 --> Oct 2025 | Trial primary completion date: Sep 2024 --> Sep 2025

Biochemical, structural, and cellular studies of a diverse panel of EGFR inhibitors revealed that the more recently developed compounds BAY-568, TAS6417, and TAK-788 inhibit EGFR insASV and insSVD in a mutant-selective manner, with BAY-568 being the most potent and selective versus wild-type (WT) EGFR. Cocrystal structures with WT EGFR reveal the binding modes of each of these inhibitors and of poziotinib, a potent but not mutantselective inhibitor, and together they define interactions shared by the mutant-selective agents. Collectively, our results show that these exon20 insertion variants are not inherently inhibitor resistant, rather they differ in their drug sensitivity from WT EGFR. However, they are similar to each other, indicating that a single inhibitor should be effective for several of the diverse exon 20 insertion variants.

Interestingly, "common mutations" were found seldom in our study population, while the uncommon variants constitute 83% of all mutations, which we assume is due to diverse Indian genetics and ethnicity and co-existing signature mutations that involve the tyrosine kinase domain of EXON20. We suggest future genome-wide association studies to identify plausible genetic polymorphisms responsible for interethnic differences in EGFR mutation, which will contribute to better treatment and prevention of NSCLCs.

P2, N=150, Active, not recruiting, Myung-Ju Ahn | Recruiting --> Active, not recruiting

This case underscores the transient efficacy of targeted therapy in SMARCA4-deficient NSCLC with concurrent EGFR mutations. It highlights the need for continuous therapeutic adjustments and emphasizes the importance of further research into effective strategies for treating this complex and challenging subset of NSCLC, as current modalities have limitations in sustained efficacy.

Among them, 16 patients received systemic chemotherapy based on etoposide, of which 13 cases could be evaluated for efficacy, 11 cases could be calculated for PFS...After SCLC transformation, the standard chemotherapy regimen for SCLC is generally used for treatment. The OS after SCLC transformation is related to the stage, and the prognosis is better in the limited stage.

P2, N=200, Recruiting, Janssen Research & Development, LLC | N=300 --> 200

P1, N=701, Active, not recruiting, Janssen Research & Development, LLC | Recruiting --> Active, not recruiting | N=460 --> 701

The establishment of tumoroids from lung cancer cell lines is feasible with various methodologies, which is promising for future tumoroid growth from clinical lung cancer samples. However, analysis of relevant markers is a prerequisite and may need to be validated for each model and cell type.

Conclusions Our study reveals a high frequency of occult EGFR mutations (Exon 19 deletion and Exon 21 L858R mutation) in non-small cell lung cancer (NSCLC) patients, particularly among male smokers and female non-smokers. These findings emphasize the importance of routine EGFR mutation testing to identify patients who may benefit from targeted therapies, ultimately improving treatment outcomes.

Interestingly, strong hydrophobic interactions were also observed with the C-terminal tail residues, such as PHE997 and ALA1000 as well as with ARG999 for the YSIPKSS peptide and most of the conjugates...Overall, our results show that the (7-DGA)2-K, di-conjugate, the (7-DGA)2-Y di-conjugate, and the neat YSIPKSS demonstrated strong and stable binding with the L858R mutant and the highly resistant triple mutant EGFR, respectively. The novel designed conjugates demonstrate potential for further optimization for laboratory studies aimed at developing new therapeutics for targeting specific EGFR mutant expressing cells.

This study will offer better perspectives on the efficacy and safety of osimertinib plus bevacizumab combination therapy in treatment-naïve recurrent or metastatic NSCLC patients harboring EGFR exon 21 L858R mutation, providing valuable guidance for clinical practice.

Recently, amivantamab and sunvozertinib have demonstrated notable efficacy as first-line treatments, and several other promising novel targeted drugs are also challenging the status quo of traditional first-line platinum-based chemotherapy regimens. These developments are anticipated to further improve survival outcomes for NSCLC patients with EGFR ex20ins mutations. Hence, this review summarizes the epidemiology, molecular attributes, detection methodologies, and therapeutic advancements for EGFR ex20ins mutations in NSCLC, and briefly discusses the mechanisms of drug resistance.

Pulmonary sarcomatoid carcinoma (PSC) is a rare disease with strong aggressiveness, low response rates to treatment, short survival span and poor prognosis, belonging to a group of non-small cell lung carcinomas (NSCLC) that remains incompletely understood. Here, we presented three PSC cases with epidermal growth factor receptor (EGFR) L858R, BRAF V600E and ALK mutations respectively, described their clinical characteristics and conducted a review of literature, in order to improve its therapeutic level, which also provided evidence-based medical evidence for driver gene screening and molecular targeted drug application in PSC patients.

P2, N=57, Active, not recruiting, Intergroupe Francophone de Cancerologie Thoracique | Trial completion date: Feb 2024 --> Dec 2024

P2, N=51, Active, not recruiting, AstraZeneca | Recruiting --> Active, not recruiting

Zorifertinib significantly improved systemic and intracranial PFS versus first-generation EGFR-TKIs; adverse events were manageable. Sequential use of zorifertinib and third-generation EGFR-TKIs showed the potential to prolong patients' survival. The results favor zorifertinib as a novel, well-validated first-line option for CNS-metastatic patients with EGFR-mutant NSCLC.

P3, N=418, Active, not recruiting, Janssen Research & Development, LLC | Trial completion date: Jan 2025 --> Dec 2025

KRAS mutations were positively associated with men and longer tumor long diameters and negatively correlated with lung adenocarcinoma (P < 0.05 for all). Our findings suggest that the EGFR mutation frequency was higher in women, non-smokers, lung adenocarcinoma, and the IA subtype in lung adenocarcinoma patients, while the KRAS mutation rate was higher in men and patients with longer tumor long diameter and lower in lung adenocarcinoma patients.

Additionally, high EMP scores were associated with papillary and acinar patterns (p = 0.0038 and p = 0.0255, respectively), whereas low EMP scores were associated with solid patterns (p = 0.0001). These results validate the reliability of our model and suggest that it can provide crucial information for rapid screening and treatment plans.

P3, N=724, Active, not recruiting, AstraZeneca | Recruiting --> Active, not recruiting | Trial primary completion date: Mar 2026 --> Apr 2027

Our results show guttiferone E to be a promising, novel and potent antitumor drug candidate for osimertinib-resistant lung cancer with EGFR L858R/T790M mutations.

P3, N=422, Completed, Merck Sharp & Dohme LLC | Active, not recruiting --> Completed

P1, N=80, Recruiting, MediLink Therapeutics (Suzhou) Co., Ltd. | Active, not recruiting --> Recruiting | Trial completion date: Dec 2025 --> Dec 2026 | Trial primary completion date: Dec 2024 --> Dec 2025

P3; Recruiting --> Active, not recruiting

Overall, by harnessing the specificity and efficacy of ASOs, we present an effective and adaptable therapeutic platform for NSCLC treatment.

Based on real-world data, osimertinib did not show a significant improvement in overall survival compared to other EGFR-TKIs as a first-line treatment for EGFR-mutated advanced non-small cell lung cancer in the Japanese (Asian) population.