EGFR exon 19 deletion

Compound 31 inhibited EGFR L858R/T790M/C797S in biochemical assays with a Ki = 2.1 nM and EGFR del19/T790M/C797S in a Ba/F3 cellular assay with an IC50 = 56.9 nM. The deuterated analogue of 31 (38) demonstrated dose-dependent tumor growth inhibition in a Ba/F3 EGFR del19/T790M/C797S CDX model by 47% at 50 mg/kg BID and 92% at 100 mg/kg BID.

This large-scale, cross-sectional study reveals a complex interplay between genetic mutations, immunological features and pre-existing conditions in NSCLC patients, offering insights that could inform personalised treatment strategies.

In RELAY, OS was not significantly improved with similar long OS durations in both treatment arms.

Both deep learning models and radiomic signature-based models offer reasonably accurate non-invasive predictions of EGFR status and its subtypes. Fusion models hold the potential to enhance noninvasive methods for predicting EGFR mutations and subtypes, presenting a more reliable prediction approach.

P3, N=354, Active, not recruiting, Takeda | Trial completion date: Dec 2024 --> Jul 2025

This case demonstrates the efficacy of osimertinib for rare EGFR mutations, aligning with literature suggesting its potential for managing such variants. Although large-scale trials are impractical due to the rarity of these mutations, this report adds valuable evidence supporting osimertinib's use, highlighting the need for comprehensive genomic profiling in NSCLC.

P1/2, N=10, Terminated, Astellas Pharma Global Development, Inc. | Phase classification: P1b/2 --> P1/2

EGFR mutations are robust biomarkers for RFS estimation in stage I invasive LUAD. Combining EGFR mutations with other actionable mutations enhances individualized RFS estimation.

P=N/A, N=923, Completed, AstraZeneca | Recruiting --> Completed

P3, N=624, Active, not recruiting, Jiangsu Hansoh Pharmaceutical Co., Ltd. | Recruiting --> Active, not recruiting | Trial primary completion date: Jan 2024 --> Jun 2024

The sensing system was able to effectively differentiate between wild-type and other mutation types, and its detection results were consistent with qPCR. The excellent performance of the sensor suggests its promising application in the diagnosis and precision treatment of NSCLC.

Osimertinib demonstrated robust response in NSCLC harboring uncommon EGFR mutations, without unanticipated safety concerns.

P2, N=30, Active, not recruiting, Dana-Farber Cancer Institute | Recruiting --> Active, not recruiting | Trial completion date: Mar 2026 --> Mar 2027 | Trial primary completion date: Feb 2025 --> Feb 2026

In this editorial we comment on the article by Ji et al. We focus specifically on the EGFR tyrosine kinase inhibitor (EGFR-TKI) treatment and the development of drug resistance to EGFR-TKIs.

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=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

Early SBRT for primary lung tumors may overcome targeted resistance in advanced EGFRm NSCLC patients combined with EGFR-TKIs without serious toxicities, especially for EGFR exon 19-del. ChiCTR-OIN-17013920.

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

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.

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

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

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

Following progression on osimertinib, a wide variety of treatment regimens were used. The continuation of osimertinib with chemotherapy in the second line was associated with increased PFS and OS.

ARAF amplification was identified in 5-8% of EGFR-TKI-resistant tumors. The possible roles of ARAF in SCLC transformation warrant further investigation.

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

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.

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.

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

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

Lung cancer development is influenced by the EGFR exon 19 747-750 deletion mutation, and the prognosis and early prediction of lung cancer are greatly affected by the amino acid profile concentrations.