Published Online:17 Oct 2022https://doi.org/10.4155/bio-2022-0150
Abstract
Background: JRF103, a novel pan-HER inhibitor, has shown potent activity against HER1, HER2, HER4 and EGFR in vitro. To support its first in-patient trial, a sensitive and rapid method was developed and validated using ultra-performance LC–MS/MS. Materials & methods: JRF103 was extracted from plasma using protein precipitation. Extracts were subjected to ultra-performance LC–MS/MS with electrospray ionization. Results: Separation of analyte was achieved using a 1.7-μm C18 column (2.1 × 50-mm internal diameter) with a gradient elution. The developed method was fully validated following the international guides. Conclusion: The developed method was sensitive, specific and suitable for measuring JRF103 concentration in patients with advanced solid tumors in the first in-patient study of JRF103.
Papers of special note have been highlighted as: • of interest; •• of considerable interest
References
- 1. Global, regional, and national cancer incidence, mortality, years of life lost, years lived with disability, and disability-adjusted life-years for 29 cancer groups, 1990 to 2017: a systematic analysis for the Global Burden of Disease Study. JAMA Oncol. 5(12), 1749–1768 (2019).
- 2. . Current cancer situation in China: good or bad news from the 2018 global cancer statistics. Cancer Commun. (Lond.) 39(1), 22 (2019).
- 3. . Epidermal growth factor receptor (EGFR) as a target in cancer therapy: understanding the role of receptor expression and other molecular determinants that could influence the response to anti-EGFR drugs. Eur. J. Cancer 39(10), 1348–1354 (2003).
- 4. . Pan-HER-targeted approach for cancer therapy: mechanisms, recent advances and clinical prospect. Cancer Lett. 439, 113–130 (2018).
- 5. . Critical update and emerging trends in epidermal growth factor receptor targeting in cancer. J. Clin. Oncol. 23(11), 2445–2459 (2005).
- 6. . Epidermal growth factor receptor targeting in cancer. Semin. Oncol. 33(4), 369–385 (2006).
- 7. . Afatinib, erlotinib and gefitinib in the first-line therapy of EGFR mutation-positive lung adenocarcinoma: a review. Onkologie 36(9), 510–518 (2013).
- 8. . Rational bases for the development of EGFR inhibitors for cancer treatment. Int. J. Biochem. Cell Biol. 39(7–8), 1416–1431 (2007).
- 9. . Acquired resistance to third-generation EGFR-TKIs and emerging next-generation EGFR inhibitors. Innovation (Camb.) 2(2), 100103 (2021).
- 10. . EGFR inhibitors: what have we learned from the treatment of lung cancer. Nat. Clin. Pract. Oncol. 2(11), 554–561 (2005).
- 11. . Mechanisms of acquired resistance to first- and second-generation EGFR tyrosine kinase inhibitors. Ann. Oncol. 29(Suppl. 1), i10–i19 (2018). • Discusses the cause of drug resistance in cancer patients and provides the basis for JRF103 development.
- 12. Mechanisms and clinical activity of an EGFR and HER2 exon 20-selective kinase inhibitor in non-small cell lung cancer. Nat. Med. 24(5), 638–646 (2018).
- 13. . Novel drugs targeting EGFR and HER2 exon 20 mutations in metastatic NSCLC. Crit. Rev. Oncol. Hematol. 148, 102906 (2020).
- 14. Poziotinib for patients with HER2 exon 20 mutant non-small-cell lung cancer: results from a phase II trial. J. Clin. Oncol. 40(7), 702–709 (2022).
- 15. Pan-cancer landscape and analysis of ERBB2 mutations identifies poziotinib as a clinically active inhibitor and enhancer of T-DM1 activity. Cancer Cell 37(3), 420 (2020).
- 16. . Identification and characterization of in silico, in vivo, in vitro, and reactive metabolites of infigratinib using LC-ITMS: bioactivation pathway elucidation and in silico toxicity studies of its metabolites. RSC Adv. 10(28), 16231–16244 (2020).
- 17. . Metabolic stability assessment of new PARP inhibitor talazoparib using validated LC-MS/MS methodology: in silico metabolic vulnerability and toxicity studies. Drug Des. Devel. Ther. 14, 783–793 (2020).
- 18. . Phase I metabolic profiling and unexpected reactive metabolites in human liver microsome incubations of X-376 using LC-MS/MS: bioactivation pathway elucidation and in silico toxicity studies of its metabolites. RSC Adv. 10(9), 5412–5427 (2020).
- 19. . Investigation of metabolic degradation of new ALK inhibitor entrectinib by LC-MS/MS. Clin. Chim. Acta 485, 298–304 (2018).
- 20. . LC-MS/MS method for the quantification of masitinib in RLMs matrix and rat urine: application to metabolic stability and excretion rate. Chem. Cent. J. 11(1), 136 (2017).
- 21. US FDA. Guidance for industry: analytical procedures and methods validation for drugs and biologics (2018). https://www.fda.gov/regulatory-information/search-fda-guidance-documents/analytical-procedures-and-methods-validation-drugs-and-biologics
- 22. European Medicines Agency. Committee for medicinal products for human use: guideline on bioanalytical method validation (2012). https://www.ema.europa.eu/en/documents/scientific-guideline/guideline-bioanalytical-method-validation_en.pdf
- 23. National Medical Products Administration. Technical guidelines for clinical pharmacokinetics of chemical drugs (2020). https://wenku.so.com/d/55a7cf5aa51b79c8ac0b76a28cb734c7
- 24. . Population pharmacokinetics of HM781-36 (poziotinib), pan-human EGF receptor (HER) inhibitor, and its two metabolites in patients with advanced solid malignancies. Cancer Chemother. Pharmacol. 75(1), 97–109 (2015). •• Discusses an assay that is important and critical for selecting the linearity range of JRF103.
- 25. Phase 1 studies of poziotinib, an irreversible pan-HER tyrosine kinase inhibitor, in patients with advanced solid tumors. Cancer Res. Treat. 50(3), 835–842 (2018). •• Indicates that JRF103 is a promising new drug.
