A Study of Amivantamab and Lazertinib Combination Therapy Versus Osimertinib in Locally Advanced or Metastatic Non-Small Cell Lung Cancer

Official Title

A Phase 3, Randomized Study of Amivantamab and Lazertinib Combination Therapy Versus Osimertinib Versus Lazertinib as First-Line Treatment in Patients With EGFR-Mutated Locally Advanced or Metastatic Non-Small Cell Lung Cancer.


The purpose of this study is to assess the efficacy of the amivantamab and lazertinib combination, compared with osimertinib, in participants with epidermal growth factor receptor (EGFR) mutation (Exon 19 deletions [Exon 19del] or Exon 21 L858R substitution) positive, locally advanced or metastatic non-small cell lung cancer (NSCLC).

Trial Description

Primary Outcome:

  • Progression-Free Survival (PFS) According to RECIST v1.1 by Blinded Independent Central Review (BICR)
Secondary Outcome:
  • Overall Survival (OS)
  • Objective Response Rate (ORR)
  • Duration of Response (DOR)
  • Progression-Free Survival After First Subsequent Therapy (PFS2)
  • Time to Symptomatic Progression (TTSP)
  • Intracranial PFS
  • Incidence and Severity of Adverse Events (AEs)
  • Number of Participants with Clinical Laboratory Abnormalities
  • Number of Participants with Vital Signs Abnormalities
  • Number of Participants with Physical Examination Abnormalities
  • Serum Concentration of Amivantamab
  • Plasma Concentration of Lazertinib
  • Number of Participants with Anti-Amivantamab Antibodies
  • Change from Baseline in Non-Small Cell Lung Cancer - Symptom Assessment Questionnaire (NCSLC-SAQ)
  • Change from Baseline in European Organization of Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC-QLQ-C30)
Worldwide, lung cancer is the most commonly diagnosed cancer. In NSCLC the most prevalent actionable driver mutations result in the activation of epidermal growth factor receptor (EGFR). Osimertinib and Lazertinib are EGFR tyrosine kinase inhibitors (TKIs). Amivantamab is a novel bispecific antibody that targets the extracellular domain of both EGFR and MET and can inhibit tumour growth driven by EGFR and mesenchymal-epithelial transition (MET) receptors. Lazertinib inhibits primary activating Exon 19dell and Exon 21 L858R substitution EGFR mutations, and the EGFR T790M+ resistance mutation. The hypothesis is that the amivantamab and lazertinib combination (Arm A) will demonstrate superior PFS compared with single-agent osimertinib (Arm B). The study consists of 3 phases: Screening Phase, Treatment Phase and Follow-up Phase. Participants will undergo response evaluation criteria in solid tumours (RECIST 1.1), pharmacokinetics, and safety evaluations (adverse events, laboratory tests, vital sign measurements, physical examinations).

View this trial on ClinicalTrials.gov

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Canadian Cancer Society

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