EGFR L858R

P3, N=358, Active, not recruiting, Allist Pharmaceuticals, Inc. | Unknown status --> Active, not recruiting

This paper consider that the patient's mental and behavioral symptoms were caused by brain and meningeal metastasis of lung cancer after excluding infectious disease and ineffective treatment of autoimmune encephalitis, and further pathological biopsy and genetic detection confirmed the diagnosis of metastatic lung adenocarcinoma with epidermal growth factor receptor (EGFR) L858R gene mutation, and the patient's symptoms were significantly improved after targeted therapy by Osimertinib...However, brain calcification in brain and meningeal metastases are often underestimated, and the consequent risk is misdiagnosis and delayed treatment. Therefore, brain and meningeal metastases manifested as brain calcification should not be ignored in patients with a history of previous tumors..

Therefore, without amplification of targets, this Cas12 assay can detect mutations in patients with advanced lung cancer. Future advancements in multiplex and high-throughput mutation detection using this assay will streamline self-diagnosis and treatment monitoring at home.

In vitro, miRNA-loaded NK-EVs demonstrated significant cytotoxicity against Osimertinib-resistant PDX (TM0019, Jackson Labs) and H1975R (with L858R mutations) lung cancer cells, with approximately 1.2 to 1.6-fold (p < 0.01) decrease in cell viability compared to NK-EVs alone. Western blot analysis showed downregulation of tumor-associated markers: PD-1/PD-L1, FOXM1, Survivin, NF-κB and others vs untreated group, p < 0.001) suggesting immune checkpoint inhibition, apoptosis and anti-inflammatory activity. These findings highlight the potential of NK-EVs as effective carriers for miRNAs in combination with chemotherapy, offering a promising therapeutic strategy for NSCLC with EGFR mutations.

P2, N=201, Active, not recruiting, Janssen Research & Development, LLC | N=300 --> 201 | Recruiting --> Active, not recruiting

Erlotinib and Doxorubicin served as the reference drugs. To further validate these findings, docking simulations of the promising derivatives 7i and 7f were conducted to assess their anticipated binding affinities with EGFR and its T790M/L858R mutants. Thus, compound 7f has the potential to be developed into a potent anticancer agent.

More importantly, it has been successfully used to detect the targets in clinical practice, requiring low-dose samples and a short time. This strategy is believed to shed new light on the applications of cancer diagnosis, treatment, and surveillance.

P3, N=318, Recruiting, Allist Pharmaceuticals, Inc. | Not yet recruiting --> Recruiting | Trial completion date: Jan 2025 --> Jan 2030 | Trial primary completion date: Dec 2023 --> Jan 2026

P1, N=14, Terminated, Allist Pharmaceuticals, Inc. | Unknown status --> Terminated; Indications have been approved for marketing

P=N/A, N=116, Terminated, Allist Pharmaceuticals, Inc. | Unknown status --> Terminated; Indications have been approved for marketing

TIL analysis of L858R-mutated tumors revealed that CD8+PD-1+ T cells and CD68+ macrophages were scarce in tumors, but in the cytokeratin-positive intra-tumoral regions, CD4+, FoxP3+, and CD204+ cells tended to be more abundant in the L858R-positive tumor area than in the negative area. Thus, PNA:DNA probes specific for EGFR-mutations can detect areas with heterogeneous EGFR mutants in whole cancer tissues and can be used to evaluate the mutation-associated TIL status in EGFR-mutant cancer tissues.

P=N/A, N=20, Not yet recruiting, Jilin Chemical Hospital; Jilin Chemical Hospital

P=N/A, N=10000, Not yet recruiting, Henan Cancer Hospital; Henan Cancer Hospital

P4, N=30, Not yet recruiting, The Fourth Hospital of Hebei Medical University; The Fourth Hospital of Hebei Medical University

P=N/A, N=1000, Not yet recruiting, West China Hospital, Sichuan University; West China Hospital, Sichuan University

P=N/A, N=992, Recruiting, Institut du Cancer de Montpellier - Val d'Aurelle | N=620 --> 992

P4, N=80, Not yet recruiting, Shandong First Medical University and Shandong Academy of Medical Sciences (Shandong Cancer Hospital Institute); Shandong First Medical University an

P=N/A, N=50, Recruiting, The Forthe Hospital of Hebei Medical University; The Forthe Hospital of Hebei Medical University

P1, N=40, Not yet recruiting, Henan Cancer Hospital; Henan Cancer Hospital

P4, N=30, Recruiting, Higher Education Mega Center Hospital of Guangdong Provincial Hospital of Chinese Medicine; Higher Education Mega Center Hospital of Guangdong Provi

P3, N=630, Not yet recruiting, Guangdong Provincial People's Hospital(Guangdong Academy of Medical Sciences); Guangdong Provincial People's Hospital(Guangdong Academy of Medical Sci

P2, N=5, Not yet recruiting, Second Xiangya Hospital of CSU; Second Xiangya Hospital of CSU

P=N/A, N=150, Not yet recruiting, Shanghai East Hospital; Shanghai East Hospital

P1, N=176, Not yet recruiting, Guangdong Provincial People's Hospital(Guangdong Academy of Medical Sciences); Guangdong Provincial People's Hospital(Guangdong Academy of Medical Sci

P2, N=122, Recruiting, The Affiliated Panyu Central Hospital of Guangzhou Medical University; The Affiliated Panyu Central Hospital of Guangzhou Medical University

The intercalation of cisplatin plus pemetrexed after the response to EGFR-TKI improved PFS but not OS compared with EGFR-TKI monotherapy as the first-line treatment for advanced NSqNSCLC harboring EGFR mutation.

P3, N=590, Active, not recruiting, Daiichi Sankyo | Trial completion date: Jun 2025 --> Jan 2026

No abstract available

Most prominent alterations were observed in EGFR (auto-phosphorylation Y1197 and 10 bi- and triantennary fucosyl-sialo glycans at N603), downstream PI3K-Akt pathway (ERBB2-T1240, MET-S990/T992, AKT-S124/S126) and integrin family (sialo-fucosyl glycans), suggesting site-specific alteration between N-glycosylation and phosphorylation interplay in the TKI resistant L858R-T790M mutant NSCLC cells. The glycoproteomic and phosphoproteomic landscape may help to unravel the complex modification alterations underlying the resistant mechanism, offering insights for improving therapeutic strategies and patient outcomes.

L-1 that shows the highest biological activity across BaF3 cell, mutant EGFR kinase and LSD1 assays due to its dual targeting of LSD1/EGFR, emerges as a promising lead compound for non-small cell lung cancer treatment. This study demonstrates that L-1 efficiently inhibits lung cancer growth in vitro and in vivo, suggesting it as a potential lead for non-small cell lung cancer treatment, highlighting the utility of virtual screening methods in discovering multi-target inhibitors and strategies for other diseases.

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

Furthermore, Piperlongumine significantly inhibited tumor growth in both Osimertinib-sensitive and resistant NSCLC xenograft models. These findings highlight the potential of Piperlongumine as an effective agent in overcoming EGFR-targeted therapy resistance and suggest new avenues for its clinical application in NSCLC treatment.

Shorter median event-free survival (EFS) in patients with an EGFR exon 18 mutation and those with TP53 exon 7 co-mutation was recorded. The EGFR status should be systematically evaluated using targeted NGS reflex testing for resected NS-NSCLC since future therapeutic decision-making could soon consider integrating the presence of co-occurring mutations.

While third-generation EGFR tyrosine kinase inhibitors (TKIs), such as osimertinib, are commonly regarded as first-line therapies, recent studies indicate that crizotinib may offer superior disease control in certain EGFR-mutant patients, particularly those who exhibit poor responses to EGFR TKIs...In patients with EGFR/ROS1 co-mutation, gefitinib is generally effective as a first-line treatment; however, its efficacy can be limited, whereas crizotinib has demonstrated improved disease control. Future research should focus on identifying optimal treatment strategies for patients with EGFR/ROS1 co-mutation to enhance patient outcomes. In conclusion, this case report not only illustrates the effectiveness of crizotinib in managing patients with EGFR/ROS1 co-mutation but also underscores the importance of personalized treatment approaches, offering valuable insights for improving clinical outcomes in NSCLC patients with complex genetic profiles.

The patient remained disease-free for 1 year following lazertinib treatment. This case suggests that salvage surgery after treatment with lazertinib may be a safe and effective approach for NSCLC with common EGFR mutations.

Subgroup analyses also showed similar tendency that 21 L858R had more clinical benefit compared to 19 Del no matter whether IO monotherapy or IO combination. For advanced EGFR mutant NSCLC patients, 21 L858R had superior IO efficacy compared with 19 Del.

This approach represents a promising alternative to tissue biopsy for molecular profiling, potentially expediting treatment decisions. While serum ddPCR showed limited utility, it may complement tissue genotyping in specific clinical scenarios.

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

Tartrate-resistant acid phosphatase-5b (TRACP-5b), a marker of bone resorption, was a biomarker for the required amount of calcium in this case. Patients with lung cancer with diffuse osteoblastic bone metastases could develop severe hypocalcemia and require long-term calcium supplementation.

P3, N=354, Active, not recruiting, Takeda | Trial completion date: Jul 2025 --> Sep 2026 | Trial primary completion date: Dec 2024 --> Sep 2026

Aumolertinib plus chemotherapy shows potential as first-line treatment for patients with EGFR-mutant advanced NSCLC, which deserves to be investigated in randomized controlled trials. CtDNA clearance may be a prognostic marker.

The investigation and comprehension of the significance of each individual EGFR mutation hold the promise for potential in cancer prevention or early diagnosis within family cohorts and understanding the mechanisms of tumorigenesis in sporadic cases.