HS-10375 / Jiangsu Hansoh Pharma - LARVOL DELTA

Recent advances in synthetic strategies of fourth-generation EGFR tyrosine kinase inhibitors under clinical trials for the treatment of resistant non-small cell lung cancer (NSCLC). (PubMed, Bioorg Chem) - "The present review summarizes recent advances in the synthetic strategies and biological profiles of fourth-generation EGFR-TK inhibitors currently undergoing clinical investigation for resistant Non-Small Cell Lung Cancer (NSCLC) to overcome the C797S mutation associated with Osimertinib. Representative clinical candidates, including TQB-3804, BPI-361175, BLU-945, BBT-176, BDTX-1535, QLH11811, HS-10375, and H002, are discussed with particular emphasis on synthetic route design, key intermediates, medicinal chemistry optimization, and pharmacological activity...In addition, advances in scaffold design, phosphine oxide incorporation, and conformationally optimized heterocyclic frameworks have contributed significantly to the development of next-generation mutant-selective inhibitors. Overall, this review provides a contemporary overview of synthetic innovations in fourth-generation EGFR inhibitor development and highlights emerging strategies for overcoming..."

Journal • Review • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR

HS-10375, a selective EGFR C797S tyrosine kinase inhibitor, in advanced non-small cell lung cancer. (PubMed, J Transl Med) - P1/2 | "HS-10375 demonstrated potent and mutant-selective activity against the EGFR C797S mutation in preclinical results, and showed an acceptable safety profile and objective response in a first-in-human phase 1 trial. Trial registration This trial is registered on China Drug Trials (CTR20220045), and ClinicalTrials.gov (NCT05435248)."

IO biomarker • Journal • Anorexia • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR

A clinical review on third and fourth generation EGFR tyrosine kinase inhibitors for the treatment of non-small cell lung cancer. (PubMed, Bioorg Med Chem) - "This review delves into the current clinical status, efficacy, safety profiles, and regulatory approvals of third-generation EGFR TKIs, including Osimertinib, Lazertinib, Furmonertinib, Aumolertinib, Rezivertinib, Befotertinib, Sunvozertinib...Notable fourth-generation candidates such as TQB3804, BPI-361175, BDTX-1535, WJ13404, QLH11811, H002, HS-10375, BBT-207, JIN-A02, and HS-10504 are highlighted for their potential to overcome the C797S mutation...By evaluating the therapeutic potential and limitations of these EGFR TKIs, this review aims to guide future research in the management of EGFR-mutant NSCLC. This acts as guiding beacon for the strategic design and development of third and fourth generation EGFR-TK inhibitors to overcome the drug resistance hurdles in the development of EGFR-TK inhibitors."

Journal • Review • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR

Hase 1/2 Study of HS-10375 in Patients With Advanced or Metastatic Non-Small-Cell Lung Cancer(NSCLC) (clinicaltrials.gov) - P1/2 | N=354 | Recruiting | Sponsor: Jiangsu Hansoh Pharmaceutical Co., Ltd.

Monotherapy • New P1/2 trial • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR