EGFR T790M

P4, N=1382, National Cancer Center/Cancer Hospital,Chinese Academy of Medical Sciences and Peking Union Medical College; National Cancer Center/Cancer Hospital,Ch

P2, N=25, Recruiting, Cancer Hospital of Chinese Academy of Medical Sciences; Cancer Hospital of Chinese Academy of Medical Sciences

Serial cell lines from a patient with EGFR L858R and MET amplification (PE5345), after resistance to osimertinib and capmatinib through gradual escalation of drug exposure in vitro (PE5345 os/cp R) and after clinical resistance to osimertinib and capmatinib (PE5867), were propagated...Osimertinib plus trametinib reversed resistance. PE5345 os/cp R overexpressed EGFR, which was inhibited by afatinib...Amivantamab induced significant ADCC against both MET-amplified EGFR TKI-resistant cancer and resistant cells after dual EGFR/MET inhibition. Understanding resistance mechanisms may provide clues for subsequent therapy.

P3, N=98, Active, not recruiting, AstraZeneca | Trial completion date: Jun 2026 --> Jun 2027

A previous analysis of the RELAY phase 3 liquid biopsy addendum demonstrated suppressed EGFR-activating mutation allele count, increased total cell-free DNA (cfDNA) concentration, and shortened cfDNA fragment size with ramucirumab (RAM) plus erlotinib (ERL) versus placebo (PL) plus ERL in patients with EGFR-mutated NSCLC. This updated analysis revealed differences in total cfDNA concentration and T790M mutation rates between ex19del and L858R. RAM plus ERL may exhibit greater antitumor effects on L858R, supporting the favorable survival benefits observed previously in patients with a L858R.

First-line Osimertinib induced a dramatic clinical and radiological response within days...This case underscores the critical difficulty of diagnosing lepidic-patterned tumors in an oncological emergency. It highlights the necessity of a multidisciplinary approach, combining cytology, radiology, and early molecular testing as a surrogate for traditional histopathology to guide urgent targeted therapy.

P2, N=60, Recruiting, Jonsson Comprehensive Cancer Center | Not yet recruiting --> Recruiting

The combination of osimertinib and crizotinib resulted in a marked clinical and metabolic response, was well tolerated, and the patient remained in remission. This rare case highlights that acquired CD74-ROS1 fusions may contribute to osimertinib resistance and suggests that combination targeted therapy may represent a potential therapeutic approach in selected patients.

Keyword analysis revealed a shift from molecular mechanisms to targeted therapies and immunotherapy approaches, with "chemotherapy", "gefitinib", and "mutations" emerging as the most frequent keywords. This study's bibliometric analysis of EGFR-mutant NSCLC immunotherapy reveals rapid growth but identifies key gaps: optimal immunotherapy-EGFR-tyrosine kinase inhibitors (TKIs) sequencing, predictive biomarkers, and resistance mechanisms beyond T790M linked to the tumor immune microenvironment. These insights guide future research to enhance therapeutic strategies in this evolving field.

Finally, case studies on Kirsten rat sarcoma virus (KRAS) G12D and epidermal growth factor receptor L858R/T790M/C797S demonstrate that several designed candidates were synthesized and exhibit nanomolar biochemical potency, underscoring the method's translational relevance. Together, these results position Diff-Shape as a powerful and generalizable approach for shape-constrained molecular generation.

P2, N=63, Completed, MedSIR | Active, not recruiting --> Completed

In a PC-9Del19/T790M/C797S xenograft model, 6g achieved significant dose-dependent tumor growth inhibition (TGI: 47.3% at 5 mg/kg; 64.2% at 10 mg/kg), markedly surpassing Osimertinib (TGI: 16.07% at 10 mg/kg), with no observed significant toxicity. These results establish 6g as a promising fourth-generation EGFR-TKI candidate with potent activity, favorable pharmacokinetics, and a high safety profile, offering a potential therapeutic strategy against Osimertinib resistance driven by the C797S mutation.