A Phase II Study of Aumolertinib Combined With Phased Chemotherapy for EGFR L858R Lung Adenocarcinoma

A Phase II Study of Aumolertinib Combined With Phased Chemotherapy for Treatment-Naïve EGFR L858R-Mutated Lung Adenocarcinoma (ACCEL Trial)

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Lung Adenocarcinoma Metastatic
• Intervention / Treatment: Drug: Aumolertinib combined with phased chemotherapy (pemetrexed and carboplatin)

• Study Type: Interventional
• Enrollment (Estimated): 50
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Yi-Ting Lin; Phone Number: 886-2-27372181; Email: 216165@h.tmu.edu.tw

Study Locations

• Taiwan
  • New Taipei City, Taiwan
    • Shuang Ho Hospital
    • Principal Investigator: Kang-Yun Lee
    • Contact: Si-Si Lee; Phone Number: 886-2-22490088; Email: s1200845@gmail.com
  • Taipei, Taiwan
    • Taipei Medical University Hospital
    • Principal Investigator: Chao-Hua Chiu
    • Contact: Yi-Ting Lin; Phone Number: 886-2-27372181; Email: 216165@h.tmu.edu.tw
    • Contact: Email: chaohuachiu@gmail.com
  • Taipei, Taiwan
    • Wanfang Hospital
    • Contact: Yi-Ting Lin; Phone Number: 886-2-27372181; Email: 216165@h.tmu.edu.tw
    • Principal Investigator: Shan-Yao Yang

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Individuals must be at least 18 years of age at the time of signing the informed consent form.
2. Participants must demonstrate the ability to understand the study procedures and provide written informed consent before any trial-specific activities begin.
3. A confirmed diagnosis of lung adenocarcinoma (LUAD) via histological or cytological examination is required. The disease must be in an advanced or metastatic stage (stage IIIB, IIIC, or IV by AJCC TNM staging system 9th edition) that is not suitable for curative-intent surgery or radiation therapy.
4. Documentation of an EGFR L858R mutation is mandatory. This status can be confirmed using tumor tissue or plasma-based molecular testing.
5. Participants must not have received prior systemic therapy for advanced or metastatic LUAD. Previous adjuvant or neoadjuvant treatments are allowed if they were completed at least 12 months before the first dose of the study medication.
6. An Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 is required. The estimated life expectancy of the participant must be at least three months.
7. Participants must have at least one measurable lesion that has not been previously irradiated, as defined by RECIST 1.1 criteria.

8. Adequate physiological function must be demonstrated within 14 days before the start of treatment, including:

   Bone Marrow: Absolute neutrophil count ≥ 1.5 x 10^9/L, platelet count ≥ 100 x 10^9/L, and hemoglobin ≥ 9.0 g/dL.

   Hepatic: Total bilirubin ≤ 1.5 x upper limit of normal (ULN); aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x ULN, or ≤ 5 x ULN if liver metastases are present.

   Renal: Serum creatinine ≤ 1.5 x ULN or a calculated creatinine clearance ≥ 45 mL/min.

9. Reproductive Safety: Participants of childbearing potential must agree to use highly effective contraception throughout the study and for a specified period after the final dose of the investigational products

Exclusion Criteria:

1. Any previous treatment with EGFR tyrosine kinase inhibitors, including first-, second-, or third-generation agents (e.g., gefitinib, afatinib, or osimertinib).
2. Patients with symptomatic or unstable central nervous system metastases. However, participants with symptomatic or unstable brain metastases who have completed local treatment and are off high-dose corticosteroids (>10 mg/d prednisone or equivalent) for at least two weeks may be considered eligible.

3. Severe Comorbidities:

   Cardiac: History of clinically significant cardiovascular disease, such as uncontrolled hypertension, congestive heart failure (NYHA Class II or higher), or a recent myocardial infarction within the last six months.

   Pulmonary: Known history of interstitial lung disease (ILD) or drug-induced ILD that required steroid treatment.

   Gastrointestinal: Malabsorption syndromes or chronic inflammatory bowel disease that could interfere with the absorption of oral aumolertinib.

4. Concomitant Infections: Active infections requiring systemic therapy. Patients with HBV infection may be eligible if their have received adequate antiviral treatment (antiviral treatment ≥ 7 days before the first dose of the study medication).
5. Medication Interference: Ongoing use of potent CYP3A4 inhibitors or inducers, as these may significantly alter the plasma concentrations of aumolertinib.
6. Other Malignancies: A history of another active primary malignancy within the last three years, except for adequately treated non-melanoma skin cancer or in situ carcinoma elsewhere.
7. Hypersensitivity: Known hypersensitivity to aumolertinib, pemetrexed, carboplatin, or any of the excipients used in these formulations.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: EGFR-TKI with phased chemotherapy	Drug: Aumolertinib combined with phased chemotherapy (pemetrexed and carboplatin); phased and fixed-cycle combination chemotherapy versus FLAURA2 study (upfront and continuous combination chemotherapy)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Molecular response	EGFR L858R mutant allele fraction in cfDNA	at 6 week and 18 week

Collaborators and Investigators

• Sponsor: Taipei Medical University Hospital
• Collaborators: Taipei Medical University
• Investigators: Principal Investigator: Chao-Hua Chiu, Taipei Medical University Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): June 9, 2026
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): December 31, 2028

Study Registration Dates

• First Submitted: May 28, 2026
• First Submitted That Met QC Criteria: May 28, 2026
• First Posted (Actual): June 3, 2026

Study Record Updates

• Last Update Posted (Actual): June 3, 2026
• Last Update Submitted That Met QC Criteria: May 28, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Chemotherapy; EGFR-TKI; Lung adenocarcinoma; EGFR L858R
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Carcinoma; Adenocarcinoma of Lung; Amino Acids, Peptides, and Proteins; Organic Chemicals; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coordination Complexes; Guanine; Hypoxanthines; Purinones; Purines; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Dicarboxylic; Pemetrexed; Carboplatin
• Other Study ID Numbers: N202602052

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No