Safety, Efficacy, and Pharmacokinetics of Almonertinib (HS-10296) in Pretreated Patients With EGFR-Mutated Advanced NSCLC: A Multicenter, Open-label, Phase 1 Trial

James Chih Hsin Yang, D. Ross Camidge, Cheng Ta Yang, Jianying Zhou, Renhua Guo, Chao Hua Chiu, Gee Chen Chang, Her Shyong Shiah, Yuan Chen, Chin Chou Wang, David Berz, Wu Chou Su, Nong Yang, Ziping Wang, Jian Fang, Jianhua Chen, Petros Nikolinakos, You Lu, Hongming Pan, Ajit ManiamLyudmila Bazhenova, Keisuke Shirai, Mohammad Jahanzeb, Maurice Willis, Nehal Masood, Naveed Chowhan, Te Chun Hsia, Hong Jian, Shun Lu

Research output: Contribution to journalArticlepeer-review

62 Citations (Scopus)


Introduction: Almonertinib (HS-10296) is a novel, third-generation EGFR tyrosine kinase inhibitor (EGFR TKI) that targets both EGFR-sensitizing and T790M resistance mutations. This first-in-human trial aimed to evaluate the safety, efficacy, and pharmacokinetics of almonertinib in patients with locally advanced or metastatic EGFR mutation-positive NSCLC that had progressed after pevious EGFR TKI therapy. Methods: This phase 1, open-label, multicenter clinical trial (NCT0298110) included dose-escalation (55, 110, 220, and 260 mg) and dose-expansion cohorts (55, 110, and 220 mg) with once daily oral administration of almonertinib. In each expansion cohort, tumor biopsies were obtained for the determination of EGFR T790M status. The safety, tolerability, antitumor activity, and pharmacokinetics of almonertinib were evaluated. Results: A total of 120 patients (26 patients in the dose-escalation cohort and 94 patients in the dose-expansion cohort) were enrolled. The maximum tolerated dose was not defined in the dose-escalation phase; the 260 mg regimen was not further evaluated in the dose-expansion phase owing to safety concerns and saturation of exposure. The most common treatment-related grade greater than or equal to 3 adverse events were increased blood creatine phosphokinase (10%) and increased alanine aminotransferase (3%). Among 94 patients with the EGFR T790M mutation in the dose-expansion cohort, the investigator-assessed objective response rate and disease control rate were 52% (95% confidence interval [CI]: 42–63) and 92% (95% CI: 84–96), respectively. Median progression-free survival was 11.0 months (95% CI: 9.5–not reached) months. Conclusions: Almonertinib is safe, tolerable and effective for patients with locally advanced or metastatic NSCLC harboring the EGFR T790M mutation who were pretreated with EGFR TKIs.

Original languageEnglish
Pages (from-to)1907-1918
Number of pages12
JournalJournal of Thoracic Oncology
Issue number12
Publication statusPublished - Dec 2020


  • EGFR T790M mutation
  • Epidermal growth factor receptor
  • non–small cell lung cancer
  • phase I trial
  • safety

ASJC Scopus subject areas

  • Oncology
  • Pulmonary and Respiratory Medicine


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