NCT07058519

A Study of Osimertinib-based Adaptive Treatment Guided by ctDNA EGFRm+ Monitoring in NSCLC

The Efficacy and Safety of Osimertinib-based Adaptive Treatment Guided by Circulating Tumour DNA (ctDNA) Epidermal Growth Factor Receptor Mutation-positive (EGFRm) Dynamic Monitoring in Locally Advanced or Metastatic EGFRm Non-small Cell Lung Cancer (NSCLC) Participants With ctDNA EGFRm Clearance After First-line Osimertinib Plus Chemotherapy: A Phase II, Multicentre, Prospective Study (Adaptive)

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 250 (estimated)
• Sponsor: Shanghai Chest Hospital · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The goal of this adaptive, interventional study is to assess the efficacy and safety of osimertinib-based adaptive treatment based on ctDNA dynamic monitoring in locally advanced or metastatic EGFRm NSCLC participants with ctDNA EGFRm clearance after osimertinib plus chemotherapy. The main questions it aims to answer are: 1) PFS during adaptive treatment period in Cohort 1 defined as from initiation of Osimertinib in adaptive period to progression per investigator assessment; 2) Time from initiation of osimertinib in adaptive period to first ctDNA EGFRm relapse or death

Detailed description

Locally advanced or metastatic EGFR mutation-positive (EGFRm) non-small cell lung cancer (NSCLC) (Stage IIIB, IIIC, IV, or recurrent) has a poor prognosis. The 5-year survival rate for metastatic disease is only 8.9%. While combination therapy with osimertinib and platinum-pemetrexed chemotherapy, as validated by the FLAURA2 trial, has demonstrated improved progression-free survival (PFS), it also introduces increased toxicity, treatment burden, and reduced quality of life. Notably, a subset of patients-approximately 25-30%-achieves long-term benefit from osimertinib monotherapy alone, highlighting the potential to personalize treatment intensity. Emerging evidence supports circulating tumor DNA (ctDNA) as a dynamic biomarker for guiding therapy. Analyses from FLAURA2 and other studies have shown that early ctDNA EGFRm clearance strongly correlates with superior PFS and can identify patients who may not require continuous combination therapy. Adaptive strategies based on ctDNA clearance have enabled treatment de-escalation in early-stage and advanced NSCLC settings, maintaining efficacy while reducing toxicity. This trial builds on that rationale, aiming to validate ctDNA-guided adaptive therapy to balance efficacy, safety, and quality of life in EGFRm NSCLC.

Conditions

• Locally Advanced or Metastatic EGFRm Non-small Cell Lung Cancer (NSCLC)

Interventions

Type	Name	Description
DRUG	Osimertinib-based adaptive treatment	Participants in Cohort 1 will receive Osimertinib-based adaptive treatment (either Osimertinib monotherapy or Osimertinib plus chemotherapy) depending on ctDNA EGFRm clearance or relapse by ctDNA EGFRm dynamic monitoring, until radiological disease progression (PD) as per RECIST v1.1 or other withdrawal criteria are met.
DRUG	Osimertinib 80 MG	Participants in Cohort 2 will receive Osimertinib 80 mg once daily (QD) plus pemetrexed maintenance every 3 weeks (Q3W) until radiological PD as per RECIST v1.1 or other withdrawal criteria are met.

Timeline

• Start date: 2025-09-23
• Primary completion: 2029-01-24
• Completion: 2029-01-24
• First posted: 2025-07-10
• Last updated: 2025-11-26

Locations

1 site across 1 country: China