rezivertinib (BPI-7711)

As of August 23, 2023, the first generation EGFR-TKIs, gefitinib, icotinib, and erlotinib; the second generation EGFR-TKIs, afatinib and dacomitinib; and the third generation EGFR-TKIs, osimertinib, almonertinib, furmonertinib and befotertinib were all approved for marketing by China National Medical Products Administration (NMPA). In addition, multiple domestic third-generation EGFR-TKIs are undergoing clinical trials, such as rezivertinib (BPI-7711), limertinib (ASK120067), and oritinib (SH-1028). Meanwhile, mobocertinib and sunvozertinib, which targets EGFR 20ins mutations, were also approved by NMPA. With the increasing variety of EGFR-TKIs approved for marketing subsequently, it brings confusion to clinicians when choosing specific medications, and there is an urgent need to develop relevant treatment guidelines. Hence, the Medical Oncology Branch of China International Exchange and Promotive Association for Medical and Health Care and the Chinese Association for Clinical Oncologists convened experts to integrate the research results of various EGFR-TKIs, and proposed the "China clinical practice guideline for epidermal growth factor receptor tyrosine kinase inhibitors in stage Ⅳ non-small cell lung cancer (version 2023)", to provide reference for better clinical practice.

In vitro experiments, Orlistat combined with BPI-7711 had reduced IC50 (508.08nM) in comparison with BPI-7711 alone (1328nM)...Meanwhile, fatty acids downregulated FASN and upregulated CPT1A expression, which may reduce the de nove synthesis of fatty acids and influence fatty acid oxidation. Conclusions This study revealed the metabolic landscape of advanced T790M-mutant NSCLC patients, providing the potential guide of personalized third-generation EGFR-TKI treatment and therapeutic target for overcoming resistance.

Rezivertinib demonstrated encouraging clinical CNS efficacy among advanced NSCLC patients with EGFR T790M mutation and CNS metastases.

Rezivertinib (BPI-7711) showed promising efficacy and a favorable safety profile for the treatment among the locally advanced or metastatic/recurrent NSCLC patients with EGFR mutation in the first-line setting.

No abstract available

Rezivertinib demonstrated promising efficacy and favorable safety profile for locally advanced or metastatic/recurrent NSCLC patients with EGFR T790M mutation.

The top three TRAEs were white blood cell count decreased (44.2%), platelet count decreased (39.5%), neutrophil count decreased (30.2%). Conclusions Rezivertinib showed promising efficacy and favorable safety for locally advanced or metastatic/recurrent NSCLC patients with EGFR mutation at first-line setting.

Rezivertinib demonstrated promising efficacy and favorable safety for locally advanced or metastatic/recurrent NSCLC patients with EGFR T790M mutation.

Rezivertinib was found to have promising efficacy with a manageable safety profile in patients with EGFR T790M-mutated advanced NSCLC. Further study is warranted.

In this review, we profiled many of the third-generation EGFR TKIs in late stage clinical development (e.g. almonertinib, lazertinib, alflutinib, rezivertinib, ASK120069, SH-1028, D-0316 and abivertinib) of their interim results of phase 1-3 trials and their chemical structures when publicly available. Additionally, we summarized the results of clinical trials that previously reported third-generation EGFR TKIs (rociletinib, olmutinib, nazartinib, maverlertinib) including phase 3 results of rociletinib and naquotinib. We further profiled the next-generation combination clinical trial design of third-generation EGFR TKIs including FLAURA2 (NCT04035486), MARIPOSA (NCT04487080), ACROSS1 (NCT04500704) and ACROSS2 (NCT04500717).