EGFR exon 20 insertion

When binding to osimertinib, ASV- and SVD-EGFR still revealed two energy minima on their free energy landscapes, but with considerably less conformational probability distribution at collective variable 2 >1.00 Å. In contrast, mobocertinib eliminated the energy minima at collective variable 2 >1.00 Å while decreasing the K745-E762 salt bridge formation rates.ConclusionsMobocertinib outperforms osimertinib in targeting specific subtypes of EGFR exon 20 insertions, highlighting its ability to restore the inactive state of this protein.

Our case highlighted the feasibility of sunvozertinib neoadjuvant therapy in EGFR ex20ins-positive NSCLC patient with locally advanced disease. Importantly, adjuvant therapy using an adequate dosage of sunvozertinib is pivotal to prevent disease flare and tumor recurrence.

Furthermore, treatment with sunvozertinib did not change protein expression or subcellular localization of ABCB1. Altogether, these data demonstrate that sunvozertinib, when combined with other conventional chemotherapeutic agents, can overcome MDR and improve therapeutic effect.

P1/2, N=315, Active, not recruiting, Dizal Pharmaceuticals | Trial completion date: Jul 2025 --> Dec 2025

In participants with atypical EGFR-mutated advanced NSCLC, amivantamab-lazertinib demonstrated clinically meaningful antitumor activity with no new safety signals.

Subsequently, the patient started gefitinib treatment, and 3 months later, the treatment effect assessment showed a partial response (PR) at regular follow-up according to RECIST evaluation criteria...Two months later, imaging examination showed that the lesions in various parts of the body were stable. Except for dryness of oral and nasal mucosa, the patient did not experience other serious adverse reactions.

P1, N=30, Active, not recruiting, Allist Pharmaceuticals, Inc. | Trial completion date: Aug 2025 --> Feb 2026

Delayed SUS incorporation of amivantamab may result in over a 1,000 preventable deaths and life-years lost among Brazilian EGFR exon 20-mutated NSCLC. Urgent real-world studies and cost-effectiveness analyses are needed.

Andamertinib at 240 mg once daily demonstrated efficacy with a manageable safety profile in previously treated patients with EGFR ex20ins-mutant NSCLC.

P3, N=308, Active, not recruiting, Janssen Research & Development, LLC | Trial completion date: Jan 2026 --> Sep 2026

Thus, MET augments amivantamab binding to EGFR and augments ADCC activity at low amivantamab concentrations. These results indicate that binding to MET contributes to the increased efficacy of amivantamab in NSCLC with common EGFR mutations.

RICTOR mutations in lung adenocarcinoma define a molecularly distinct subgroup characterized by preferential co-occurrence with EGFR, KRAS, and TP53, as well as a broader spectrum of genomic alterations. These findings support the view that RICTOR functions within complex oncogenic contexts and warrant further investigation in larger, multi-institutional cohorts.