Aumolertinib Combined With Phased Chemotherapy for EGFR L858R Lung Adenocarcinoma

Background: While third-generation EGFR tyrosine kinase inhibitors (TKI) like aumolertinib have significantly improved outcomes for patients with advanced lung adenocarcinoma, those harboring the L858R mutation still experience inferior prognosis compared to those with exon 19 deletions. Recent evidence suggests that combining TKIs with chemotherapy improves progression-free survival (PFS), but universal application of this combination exposes all patients to cytotoxic toxicity, even those who might thrive on TKI monotherapy alone. Circulating cell-free DNA (cfDNA) and minimal residual disease monitoring offer a dynamic window to identify which patients truly require treatment intensification. Objectives: The primary objective is to evaluate the predictive value of early molecular response by determining the association between the change in EGFR mutant allele fraction in cfDNA after a 6-week aumolertinib lead-in induction phase (T1) and a 4-cycle combination chemotherapy (T2) with clinical PFS. Secondary objectives include assessing overall response rates (ORR), disease control rate (DCR), safety, and the dynamics of EGFR mutant allele fraction and circulating immune cell profiles. Study Design: This is a prospective, single-arm, multicenter, phase II clinical trial enrolling 50 evaluable patients. The study utilizes a three-phase treatment framework: * Induction Phase: Aumolertinib monotherapy (110 mg/day) once daily for 6 weeks. * Consolidation Phase: Combination of aumolertinib (110 mg/day) once daily with pemetrexed (500 mg/m²) and carboplatin (AUC 5) once every three weeks for 4 cycles. * Maintenance Phase: Aumolertinib monotherapy once daily until disease progression. Endpoints: The primary efficacy endpoint is Progression-Free Survival (PFS). Molecular efficacy will be measured via the Molecular Clearance Rate (MCR) and Molecular Response Rate (MRR) at baseline (T0), post-induction (T1), and post-chemotherapy (T2). Safety will be graded according to CTCAE v5.0. Conclusion and Significance: This trial aims to establish a molecularly driven framework for personalized lung cancer management, seeking to maximize efficacy for high-risk patients while providing the foundation to spare molecular responders from unnecessary chemotherapy in the future. The results will serve as the base for the design of future confirmatory phase III trials.

NCT Number	NCT07624487
Lead Sponsor	Taipei Medical University Hospital Collaborators: Taipei Medical University
Conditions	Lung Adenocarcinoma Metastatic
Enrollment	50 participants
Start Date	2026-06-09
Primary Completion	2028-12-31 (estimated)
Study Completion	2028-12-31 (estimated)
Updated on ClinicalTrials.gov	2026-06-18