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Profiling Sensitivity to Targeted Therapies in EGFR-Mutant NSCLC Patient-Derived Organoids
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Amivantamab plus lazertinib in osimertinib-relapsed EGFR-mutant advanced non-small cell lung cancer: a phase 1 trial

Byoung Chul Cho1, Dong-Wan Kim2, Alexander I Spira3

  • 1Division of Medical Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Republic of Korea. CBC1971@yuhs.ac.

Nature Medicine
|September 14, 2023
PubMed

Insights

Combining amivantamab and lazertinib shows promise for non-small cell lung cancer (NSCLC) patients resistant to EGFR TKIs. This combination therapy offers a potential new treatment option for advanced NSCLC, improving anti-tumor activity.

Area of Science:

  • Oncology
  • Pharmacology
  • Biotechnology

Background:

  • Epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) frequently develops resistance to third-generation EGFR tyrosine kinase inhibitors (TKIs).
  • There are currently no approved targeted treatments for patients who relapse after osimertinib therapy.
  • This presents a critical unmet need for effective treatment strategies in advanced NSCLC.

Purpose of the Study:

  • To evaluate the safety and efficacy of combining amivantamab (an EGFR-MET bispecific antibody) with lazertinib (a third-generation EGFR TKI).
  • To assess the anti-tumor activity of this combination in patients with EGFR-mutant NSCLC who progressed on third-generation TKI monotherapy.
  • To identify potential predictive biomarkers for treatment response.

Main Methods:

  • An open-label, dose-escalation and dose-expansion phase 1 trial (CHRYSALIS cohort E).
  • Patients with EGFR-mutant NSCLC, TKI-resistant and chemotherapy-naive, were enrolled.
  • Safety, overall response rate (ORR), progression-free survival (PFS), and overall survival (OS) were assessed. Biomarker analyses included next-generation sequencing and immunohistochemistry.

Main Results:

  • The combination of amivantamab and lazertinib demonstrated a manageable safety profile, consistent with individual agent use, with few grade ≥3 events.
  • In an exploratory cohort (n=45), the investigator-assessed ORR was 36% (95% CI, 22-51).
  • Median duration of response was 9.6 months, and median PFS was 4.9 months. High EGFR and/or MET expression emerged as potential predictive biomarkers.

Conclusions:

  • The combination of amivantamab and lazertinib is a potential therapeutic option for EGFR-mutant NSCLC patients with resistance to third-generation TKIs.
  • Further validation of high EGFR and/or MET expression as predictive biomarkers is warranted through prospective studies.
  • This combination addresses a significant unmet need in the osimertinib-relapsed setting.

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