Primary Tumor Resection Plus Osimertinib in Advanced EGFR-mutant Non-small Cell Lung Cancer

NCT07177092 | Not Yet Recruiting Phase 2 DMC

• 1 other identifier: ES-2025-157-02
• Study Type: interventional
• Target: 118
• Locations: 0 countries
• Sites: N/A

Brief Summary

This study is designed to explore whether resecting the primary lung cancer, followed by osimertinib, can improve outcomes for patients with advanced non-small cell lung cancer (NSCLC) harboring sensitizing EGFR mutations (exon 19 deletion or L858R). Patients with stage III-IV NSCLC will be included and randomly assigned to receive either surgery to remove the primary lung cancer followed by osimertinib, or osimertinib alone. All patients will continue treatment until disease progression or they need to stop for another reason. The primary outcome being studied is progression-free survival (PFS). Secondary outcomes include overall survival (OS), objective response rate (ORR), disease control rate (DCR), adverse effects (AEs), serious adverse effects (SAEs) and quality of life (QoL). The findings from this study may help determine whether surgery combined with EGFR tyrosine kinase inhibitor (TKI) provides more benefit than EGFR-TKI alone for patients with EGFR-mutant advanced NSCLC.

Conditions

Non-Small Cell Lung Cancer; EGFR

Keywords

Non-Small Cell Lung Cancer; EGFR; Randomized controlled trial; Surgery

Outcome Measures

Primary Outcomes (1)

• Progression-free Survival

  Progression-free survival is defined as the time from randomization to the first documentation of disease progression or death from any cause, whichever occurs first. Disease progression will be assessed by the Independent Radiology Review Committee according to RECIST version 1.1 criteria.

  From randomization until the first documentation of disease progression or death from any cause, whichever occurs first (up to 5 years).

Secondary Outcomes (6)

• Overall Survival

  Randomization to death from any cause (up to 5 years).

• Objective Response Rate

  Randomization until disease progression or death, which ever occurs first (up to 5 years).

• Disease Control Rate

  Randomization until disease progression or death, which ever occurs first (up to 5 years).

• Adverse Events

  From randomization to disease progression or death (up to 5 years).

• Quality of Life (QoL) evaluated by European Organisation for Research and Treatment of Cancer core quality of life questionnaire (EORTC QLQ-C30)

  Randomization until disease progression or death, which ever occurs first (up to 5 years).

Study Arms (2)

Control Group

ACTIVE COMPARATOR

Participants will receive oral osimertinib at a dose of 80 mg once daily, continued until disease progression or the occurrence of unacceptable toxicity.

Drug: Osimertinib

Intervention Group

EXPERIMENTAL

Participants will first undergo cytoreductive surgery. After adequate postoperative recovery for 4-6 weeks, they will receive oral osimertinib at a dose of 80 mg once daily, continued until disease progression or the occurrence of unacceptable toxicity.

Procedure: Surgery; Drug: Osimertinib

Interventions

Surgery PROCEDURE

① Preoperative evaluation must confirm resectability. Thoracoscopic minimally invasive surgery will be performed, with the surgical approach selected according to disease conditions, such as lobectomy, segmentectomy, wedge resection, or sleeve resection; ② Systematic mediastinal lymph node dissection or lymph node sampling (based on preoperative imaging and intraoperative evaluation) must be performed; ③ Postoperative recovery must be adequate (postoperative complications ≤ Clavien-Dindo grade II).

Intervention Group

Osimertinib DRUG

Dose: 80 mg orally, once daily, until disease progression or the occurrence of unacceptable toxicity. The dose should be administered at approximately the same time each day, at 24-hour intervals.

Control Group; Intervention Group

Eligibility Criteria

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

You may qualify if:

• Age 18-75 years, no restriction on sex.
• Histologically or cytologically confirmed stage III-IV non-squamous NSCLC, unresectable as assessed by multidisciplinary team (MDT).
• Presence of EGFR exon 19 deletion (19Del) or L858R mutation, confirmed by ARMS-PCR, NGS, or other validated methods.
• No prior systemic therapy for lung cancer.
• ECOG performance status of 0-1.
• Estimated life expectancy of at least 6 months.
• Primary lung tumor size ≥1 cm, with at least one measurable lesion remaining after resection according to RECIST v1.1 criteria.
• Adequate organ function, including:
• ① Hematologic function: absolute neutrophil count ≥1.5 × 10⁹/L; platelet count ≥100 × 10⁹/L; hemoglobin ≥9.0 g/dL.
• ② Hepatic function: ALT and AST ≤2.5 × ULN (≤5 × ULN if liver metastases are present); total bilirubin ≤1.5 × ULN.
• ③ Renal function: serum creatinine ≤1.5 × ULN, or creatinine clearance ≥50 mL/min (Cockcroft-Gault formula).
• Adequate pulmonary function (must meet at least one of the following to ensure postoperative reserve):
• ① FEV1 ≥1.2 L (or ≥40% of predicted value);
• ② FEV1/FVC ≥0.7, to exclude severe obstructive ventilatory dysfunction;
• ③ DLCO (diffusing capacity for carbon monoxide) ≥40% of predicted value, to assess diffusion capacity.

You may not qualify if:

• Presence of any other known EGFR mutations.
• Histological evidence of mixed small-cell lung cancer (SCLC) or history of transformation to SCLC.
• Immunodeficiency: history of primary immunodeficiency disorders, or prior allogeneic organ or bone marrow transplantation.
• Active brain metastases. Patients with adequately treated brain metastases may be eligible if they are neurologically stable for at least 2 weeks before enrollment, and are either not requiring corticosteroids or receiving a stable or decreasing dose of ≤10 mg prednisone (or equivalent) once daily.
• Pregnancy.
• Any serious comorbid condition that, in the opinion of the investigator, may interfere with participation in the study or interpretation of study results, including but not limited to: uncontrolled systemic diseases, psychiatric illness, active or uncontrolled infections, or other abnormal findings from laboratory or clinical examinations.

Sponsors & Collaborators

• Jianxing He: lead

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Surgical Procedures, Operative; osimertinib

Condition Hierarchy (Ancestors)

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

Central Study Contacts

Jianxing He, Ph.D

CONTACT

86+020-83062807; drjianxing.he@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: September 6, 2025
• First Posted: September 16, 2025
• Study Start: September 8, 2025
• Primary Completion (Estimated): October 1, 2028
• Study Completion (Estimated): December 1, 2030
• Last Updated: September 16, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share