Postoperative EGFR-TKI Therapy forContralateral Pulmonary Nodules in Patients With EGFR-Mutant NSCLC（ARMOR2501）

NCT06924398 | Recruiting Phase 2

• 1 other identifier: B2025-011-01
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

Brief Summary

Background Synchronous multifocal primary lung cancer (sMPLC) presents a therapeutic challenge, particularly for bilateral lesions. While surgical resection is standard for unilateral sMPLC, bilateral surgery carries high perioperative risks. This study evaluates postoperative adjuvant therapy with almonertinib, a third-generation EGFR-TKI, to reduce secondary surgery rates by targeting residual contralateral lesions in EGFR-mutant NSCLC patients. Objective

• Primary: Assess the secondary surgery rate within one year after three months of almonertinib therapy.
• Secondary: Evaluate tumor response (ORR, EGFR-TKI response rate), survival outcomes (DFS, OS), treatment safety, and surgical feasibility post-therapy. Study Design
• Phase: Single-arm, open-label, phase II trial.
• Population: 32 patients with bilateral sMPLC (EGFR exon 19 deletion/L858R mutations) after unilateral resection.
• Intervention: Oral almonertinib (110 mg/day) for three months, initiated 4-10 weeks post-surgery.
• Endpoints:
• Primary: Proportion requiring secondary surgery due to lesion persistence/progression.
• Secondary: ORR (RECIST 1.1), DFS, OS, adverse events (CTCAE v5.0), and safety of delayed surgery.
• Inclusion Criteria:
• sMPLC diagnosis (MM/ACCP criteria), T1-2N0M0 primary lesion, residual contralateral nodules (≥8 mm, confirmed malignant).
• ECOG 0-1, age 18-75 years, compliance with follow-up.
• Exclusion Criteria: Metastasis, severe organ dysfunction, prior malignancies (5 years), or concurrent QT-prolonging drugs. Statistical Analysis
• Sample size calculated (α=0.05, power=0.95) to detect a reduction in secondary surgery rate from 100% (baseline) to 90%, accounting for 10% dropout.
• Survival analysis via Kaplan-Meier curves and Cox regression; descriptive statistics for response rates. Safety Monitoring
• Adverse events graded by CTCAE v5.0, including interstitial lung disease (ILD), cardiac toxicity, and laboratory abnormalities. Dose adjustments (55 mg) or discontinuation mandated for grade ≥3 events. Ethics and Compliance
• Conducted per Good Clinical Practice (GCP) and Declaration of Helsinki.
• Informed consent required; independent review committee (IRC) evaluates imaging outcomes. Expected Outcomes
• Almonertinib may reduce secondary surgery rates by suppressing residual lesions, supported by prior efficacy in NSCLC (median PFS: 19.3 months in AENEAS trial).
• Results will inform postoperative management strategies for bilateral sMPLC. Timeline Enrollment and preliminary efficacy analysis to conclude by December 2025. Conclusion ARMOR2501 aims to validate almonertinib's role in minimizing repeat surgeries for EGFR-mutant sMPLC, balancing efficacy and safety. Successful outcomes could establish a novel adjuvant paradigm for high-risk patients.

Conditions

Lung Cancer (NSCLC)

Keywords

Lung Cancer

Outcome Measures

Primary Outcomes (1)

• Secondary Surgery Rate

  The proportion of enrolled patients who, following the completion of a three-month EGFR-TKI treatment regimen, undergo surgical resection of residual lesions due to either disease progression or the persistence of lesions.

  From enrollment to end of the completion of a three-month EGFR-TKI treatment regimen

Secondary Outcomes (5)

• EGFR-TKI Response Rate

  From enrollment to end of the completion of a three-month EGFR-TKI treatment regimen

• Objective Response Rate (ORR)

  From enrollment to end of the completion of a three-month EGFR-TKI treatment regimen

• Overall Survival (OS)

  Defined as the duration from the date of patient enrollment to all-cause mortality.

• Disease-Free Survival (DFS)

  Defined as the interval from patient enrollment to the first confirmed occurrence of disease recurrence, progression, or mortality.

• Treatment-Related Adverse Events:

  From enrollment to the completion of adjuvant therapy

Study Arms (1)

Study arm

EXPERIMENTAL

A total of 32 patients with bilateral operable sMPLC will be prospectively enrolled. After unilateral tumor resection and confirmation of EGFR mutation positivity, they will be included in the study. Before formal enrollment, participants must be completely free from perioperative complications or have recovered from any complications. Enrolled patients will undergo baseline follow-up within 4 to 10 weeks postoperatively and start a three-month EGFR-TKI treatment on the same day. Patients will receive a CT follow-up at the end of the three-month treatment period. If they experience intolerable treatment-related adverse effects, EGFR-TKI treatment will be discontinued. If the lesion persists after three months, a multidisciplinary team will determine whether to proceed with surgical treatment.

Drug: Postoperative EGFR-TKI Therapy

Interventions

Postoperative EGFR-TKI Therapy DRUG

A total of 32 patients with bilateral operable sMPLC will be prospectively enrolled. After unilateral tumor resection and confirmation of EGFR mutation positivity, they will be included in the study. Before formal enrollment, participants must be completely free from perioperative complications or have recovered from any complications. Enrolled patients will undergo baseline follow-up within 4 to 10 weeks postoperatively and start a three-month EGFR-TKI treatment on the same day. Patients will receive a CT follow-up at the end of the three-month treatment period. If they experience intolerable treatment-related adverse effects, EGFR-TKI treatment will be discontinued. If the lesion persists after three months, a multidisciplinary team will determine whether to proceed with surgical treatment.

Study arm

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• ）Patients diagnosed with sMPLC (according to MM/ACCP clinical criteria). Preoperative chest CT (1mm slice thickness) reveals multiple bilateral lesions, all meeting surgical criteria \[≥8mm (pure ground-glass nodules (GGNs) must be \>1cm) and unchanged after standard anti-inflammatory treatment\].
• ）Patients received standard anti-inflammatory treatment before surgery.
• ）The primary lesion in the operated lung is staged as T1-2N0M0.
• ）Patients have undergone surgical resection of one side of the lung, with pathology confirming adenocarcinoma and an EGFR-sensitive mutation (exon 19 deletion or exon 21 L858R point mutation).
• ）After unilateral resection, the contralateral lung must have at least one suspected malignant residual nodule \[≥8mm (pure GGNs must be \>1cm) and \<3cm, unchanged after standard anti-inflammatory treatment\], which must be confirmed as malignant by a qualified radiologist and thoracic surgeon.
• ）ECOG performance status (PS) score of 0-1.

You may not qualify if:

• ）Patients with lymph node metastasis or distant metastasis.
• ）Patients with severe heart, lung, liver, or kidney dysfunction who cannot tolerate surgery.
• ）Patients with a history of other malignancies within five years (except effectively controlled basal cell carcinoma, cervical carcinoma in situ, ductal carcinoma in situ of the breast, papillary thyroid carcinoma, and superficial bladder tumors).
• ）Patients taking medications known to prolong the QTc interval or induce ventricular tachycardia who need to continue such medications during the study period.
• ）Patients with a history of interstitial lung disease (ILD) or drug-induced ILD.
• ）Patients with severe gastrointestinal dysfunction, diseases, or clinical symptoms that may affect drug intake, transport, or absorption.
• ）Patients with active hepatitis B, hepatitis C, or HIV infections.
• ）Pregnant or lactating women or women of childbearing potential who have not taken contraceptive measures.
• ）Patients with uncontrolled neurological or psychiatric disorders or mental illnesses.
• ）Patients participating in other clinical trials or expected to receive other anti-tumor treatments during this trial.
• ）Other conditions deemed unsuitable for the study by the investigators

Sponsors & Collaborators

• Sun Yat-sen University: lead

Study Sites (1)

Sun Yat-sen University Cancer Center

Guangzhou, Guangdong, 510060, China

RECRUITING

Related Publications (6)

• Yang Z, Zhou B, Guo W, Peng Y, Tian H, Xu J, Wang S, Chen X, Hu B, Liu C, Wang Z, Li C, Gao S, He J. Genomic characteristics and immune landscape of super multiple primary lung cancer. EBioMedicine. 2024 Mar;101:105019. doi: 10.1016/j.ebiom.2024.105019. Epub 2024 Feb 15.

  PMID: 38364701 BACKGROUND

• Cheng B, Li C, Zhao Y, Li J, Xiong S, Liang H, Liu Z, Zeng W, Liang W, He J. The impact of postoperative EGFR-TKIs treatment on residual GGO lesions after resection for lung cancer. Signal Transduct Target Ther. 2021 Feb 21;6(1):73. doi: 10.1038/s41392-020-00452-9. No abstract available.

  PMID: 33611336 BACKGROUND

• Ginsberg RJ, Rubinstein LV. Randomized trial of lobectomy versus limited resection for T1 N0 non-small cell lung cancer. Lung Cancer Study Group. Ann Thorac Surg. 1995 Sep;60(3):615-22; discussion 622-3. doi: 10.1016/0003-4975(95)00537-u.

  PMID: 7677489 BACKGROUND

• Feng G, Jia Y, Zhao G, Meng F, Wang T. Risk factors for postoperative pulmonary complications in elderly patients undergoing video-assisted thoracoscopic surgery lobectomy under general anesthesia: a retrospective study. BMC Surg. 2024 May 14;24(1):153. doi: 10.1186/s12893-024-02444-w.

  PMID: 38745149 BACKGROUND

• Griffioen GH, Lagerwaard FJ, Haasbeek CJ, Smit EF, Slotman BJ, Senan S. Treatment of multiple primary lung cancers using stereotactic radiotherapy, either with or without surgery. Radiother Oncol. 2013 Jun;107(3):403-8. doi: 10.1016/j.radonc.2013.04.026. Epub 2013 Jun 6.

  PMID: 23746675 BACKGROUND

• Jiang L, He J, Shi X, Shen J, Liang W, Yang C, He J. Prognosis of synchronous and metachronous multiple primary lung cancers: systematic review and meta-analysis. Lung Cancer. 2015 Mar;87(3):303-10. doi: 10.1016/j.lungcan.2014.12.013. Epub 2015 Jan 14.

  PMID: 25617985 BACKGROUND

MeSH Terms

Conditions

Lung Neoplasms; Carcinoma, Non-Small-Cell Lung

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms

Study Officials

• Hong Yang, PhD

  Sun Yat-sen University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Hong Yang, PhD

CONTACT

86 13560405144; yanghong@sysucc.org.cn

Zhichao Li, MD

CONTACT

+8615626140781; lizc1@sysucc.org.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof

Model Details: A total of 32 patients with bilateral operable sMPLC will be prospectively enrolled. After unilateral tumor resection and confirmation of EGFR mutation positivity, they will be included in the study. Before formal enrollment, participants must be completely free from perioperative complications or have recovered from any complications. Enrolled patients will undergo baseline follow-up within 4 to 10 weeks postoperatively and start a three-month EGFR-TKI treatment on the same day. Patients will receive a CT follow-up at the end of the three-month treatment period. If they experience intolerable treatment-related adverse effects, EGFR-TKI treatment will be discontinued. If the lesion persists after three months, a multidisciplinary team will determine whether to proceed with surgical treatment.

Study Record Dates

• First Submitted: April 6, 2025
• First Posted: April 11, 2025
• Study Start: April 20, 2025
• Primary Completion: December 1, 2025
• Study Completion: December 31, 2025
• Last Updated: June 10, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)