EGFR mutation

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

To our knowledge, ARIA is the largest real-world study of dacomitinib's efficacy and safety. Final analysis of this study showed substantial clinical efficacy of dacomitinib and revealed treatment patterns, such as starting dose, in the real world. Safety data were consistent with dacomitinib's known safety profile. These results support first-line dacomitinib use in Asian patients with EGFR mutation-positive advanced NSCLC.

Notably, MAP2K1 E102-I103 deletion was frequently observed in pre-invasive samples, which endowed alveolar type II cells with increased growth potential and initiated tumor formation, suggesting that it is a potential driver mutation of LUAD. In summary, our study highlights key molecular changes during the stepwise progression of LUAD, provides insights into the identification of novel therapeutic targets, and helps to define the curative time window for this disease.

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

In this large real-world comparative effectiveness study using target trial emulation, first-line osimertinib was associated with substantially prolonged OS and a favorable safety profile, including lower rates of severe infections and hospitalizations, compared with first-generation EGFR-TKIs in patients with metastatic EGFR-mutant NSCLC.

The pro-tumorigenic activity of OR cells was diminished by depletion of EMT-dependent secreted proteins or the EMT-activating transcription factor ZEB1. These findings identify paracrine mechanisms by which OR cells drive LUAD progression.

A 41-year-old male with metastatic lung adenocarcinoma received gefitinib as the first-line treatment. Drug binding dynamics simulation indicated reduced binding activity of osimertinib to L747_T751del and K754E mutation sites as compared to other third- or second-generation EGFR-targeted inhibitors. This study provides the first comprehensive investigation of the L747_T751del and in cis K754E mutation and its interaction with EGFR-targeted inhibitors, offering valuable clinical guidance for treating uncommon EGFR exon 19 mutations.

In this study, we found that EGFR-TKI, including gefitinib and osimertinib, impaired WWP2-mediated proteasomal degradation of LAPTM4B. These compounds synergistically enhance the efficacy of EGFR-TKIs in NSCLC models in vitro and in vivo, with minimal toxicity. Integrative analyses of patient tissue samples, cellular models, an animal model, and cancer databases highlight the critical role of the LAPTM4B-ATP1A1-lysosomal acidification axis in EGFR-TKI resistance, providing a promising therapeutic avenue for overcoming resistance in EGFR-mutant NSCLC.

Here, we present the case of a patient with advanced HER2 mutant NSCLC who achieved complete pathologic response to chemoimmunotherapy. Our observation suggests that not all driver mutations equally drive resistance to immunotherapy, and some molecular events, such as HER2 mutations, need additional investigations.

P4, N=136, Recruiting, Nikolaj Frost MD | Trial primary completion date: Oct 2025 --> Feb 2026

This study provides critical data on the epidemiology and prognosis of lung cancer in Vietnam, highlighting the role of personalized treatment approaches in improving clinical outcomes. These findings underscore the urgent need for integrated public health strategies to enhance early detection and access to advanced therapies, thereby reducing the lung cancer burden in Vietnam.