Evaluation of combination treatment with DS-1205c, an AXL kinase inhibitor, and osimertinib in metastatic or unresectable EGFR-mutant non-small cell lung cancer: results from a multicenter, open-label phase 1 study

James Chih Hsin Yang*, Wu Chou Su, Chao Hua Chiu, Her Shyong Shiah, Kang Yun Lee, Te Chun Hsia, Makiko Uno, Nigel Crawford, Hiroshi Terakawa, Wen Chi Chen, Gensuke Takayama, Ching Hsu, Ying Hong, Carline Saintilien, Joseph McGill, Gee Chen Chang

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

2 Scopus citations

Abstract

The objective of this study was to evaluate the safety and tolerability of DS-1205c, an oral AXL-receptor inhibitor, in combination with osimertinib in metastatic or unresectable EFGR-mutant non-small cell lung cancer (NSCLC) patients who developed disease progression during EGFR tyrosine kinase inhibitor (TKI) treatment. An open-label, non-randomized phase 1 study was conducted in Taiwan, in which 13 patients received DS-1205c monotherapy at a dosage of 200, 400, 800, or 1200 mg twice daily for 7 days, followed by combination treatment with DS-1205c (same doses) plus osimertinib 80 mg once daily in 21-day cycles. Treatment continued until disease progression or other discontinuation criteria were met. At least one treatment-emergent adverse event (TEAE) was reported in all 13 patients treated with DS-1205c plus osimertinib; with ≥ 1 grade 3 TEAE in 6 patients (one of whom also had a grade 4 increased lipase level), and 6 patients having ≥ 1 serious TEAE. Eight patients experienced ≥ 1 treatment-related AE (TRAE). The most common (2 cases each) were anemia, diarrhea, fatigue, increased AST, increased ALT, increased blood creatinine phosphokinase, and increased lipase. All TRAEs were non-serious, with the exception of an overdose of osimertinib in 1 patient. No deaths were reported. Two-thirds of patients achieved stable disease (one-third for > 100 days), but none achieved a complete or partial response. No association between AXL positivity in tumor tissue and clinical efficacy was observed. DS-1205c was well-tolerated with no new safety signals in patients with advanced EGFR-mutant NSCLC when administered in combination with the EFGR TKI osimertinib. ClinicalTrials.gov; NCT03255083.

Original languageEnglish
Pages (from-to)306-316
Number of pages11
JournalInvestigational New Drugs
Volume41
Issue number2
DOIs
StatePublished - 04 2023

Bibliographical note

© 2023. The Author(s).

Keywords

  • AXL kinase inhibitor
  • Advanced non-small cell lung cancer
  • DS-1205c
  • Epidermal growth factor receptor
  • Inoperable non-small cell lung cancer
  • Oncology
  • Humans
  • Disease Progression
  • ErbB Receptors/genetics
  • Protein Kinase Inhibitors/adverse effects
  • Lung Neoplasms/drug therapy
  • Carcinoma, Non-Small-Cell Lung/drug therapy
  • Antineoplastic Agents/adverse effects
  • Mutation
  • Aniline Compounds/adverse effects

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