Osimertinib With or Without Primary Lung Tumor Resection for EGFR-Mutant Oligometastatic Non-Small Cell Lung Cancer

NCT07738172 | Not Yet Recruiting Phase 3

• 1 other identifier: 202605130RINE
• Study Type: interventional
• Target: 154
• Locations: 1 country
• Sites: 1

Brief Summary

Osimertinib is a standard first-line treatment for patients with metastatic non-small cell lung cancer harboring an epidermal growth factor receptor exon 19 deletion or exon 21 L858R mutation. Although osimertinib can provide effective disease control, most patients eventually experience disease progression, and the primary lung tumor may remain an important site of treatment resistance. This multicenter, randomized, open-label phase III trial will evaluate whether surgical removal of the primary lung tumor, in addition to continued osimertinib treatment, prolongs progression-free survival in patients with EGFR-mutated oligometastatic non-small cell lung cancer. All participants will initially receive osimertinib 80 mg orally once daily for 12 weeks. Participants who have a partial response or stable disease according to RECIST version 1.1 and remain suitable for surgery will be randomly assigned in a 1:1 ratio to continue osimertinib alone or to undergo primary lung tumor resection followed by resumption of osimertinib. The study will also evaluate overall survival, safety, pathologic response, quality of life, patterns of disease progression, and changes in molecular biomarkers.

Conditions

Lung Neoplasms, Non-Small Cell Lung Cancer

Keywords

non-small cell lung cancer (NSCLC); EGFR mutation; stage IV non-small-cell lung cancer; Osimertinib; Primary tumor resection; Oligometastatic non-small cell lung cancer; Local consolidative therapy

Outcome Measures

Primary Outcomes (1)

• Progression-Free Survival

  Progression-free survival is defined as the time from randomization to the first documented occurrence of disease progression according to RECIST version 1.1 or death from any cause, whichever occurs first. Participants without an event will be censored at the date of their last adequate disease assessment.

  From randomization to disease progression or death, assessed up to 24 months after randomization.

Secondary Outcomes (4)

• Overall Survival

  From randomization to death from any cause, assessed up to 48 months after randomization.

• Number of Participants With Treatment-Related Adverse Events

  From the first dose of osimertinib through 28 days after the last dose

• Pathologic Response of the Primary Lung Tumor

  At primary lung tumor resection, generally within 12 weeks after randomization

• Change From Baseline in Quality-of-Life Score

  Before osimertinib induction, at week 12 before randomization, and at 12 and 24 months after randomization.

Other Outcomes (7)

• Local-Regional Progression-Free Survival

  From randomization until locoregional progression or death, assessed up to 5 years

• Distant Metastasis Progression-Free Survival

  Time Frame: From randomization until distant progression or death, assessed up to 5 years

• Brain Metastasis Progression-Free Survival

  From randomization until intracranial progression or death, assessed up to 5 years

Study Arms (2)

Osimertinib Alone

ACTIVE COMPARATOR

Participants will receive osimertinib 80 mg orally once daily for 12 weeks before randomization. After randomization, participants assigned to this arm will continue osimertinib 80 mg once daily until disease progression, unacceptable toxicity, withdrawal, or another protocol-defined reason for treatment discontinuation.

Drug: Osimertinib

Osimertinib Plus Primary Tumor Resection

EXPERIMENTAL

Participants will receive osimertinib 80 mg orally once daily for 12 weeks before randomization. After randomization, participants assigned to this arm will undergo therapeutic resection of the primary lung tumor. Osimertinib will generally be resumed 1 to 2 weeks after surgery when wound healing is considered adequate and will be continued until disease progression, unacceptable toxicity, withdrawal, or another protocol-defined reason for treatment discontinuation.

Procedure: Primary Tumor Resection; Drug: Osimertinib

Interventions

Primary Tumor Resection PROCEDURE

Participants assigned to the experimental arm will undergo therapeutic resection of the primary lung tumor after randomization. Acceptable procedures include lobectomy, sleeve lobectomy, bilobectomy, segmentectomy, and wedge resection. The surgical approach may include video-assisted thoracic surgery or thoracotomy. Pneumonectomy and sleeve pneumonectomy are not permitted. The procedure is intended to achieve maximal regional disease control and tumor-free resection margins whenever feasible.

Osimertinib Plus Primary Tumor Resection

Osimertinib DRUG

Osimertinib will be administered orally at a dose of 80 mg once daily as first-line systemic therapy. Treatment will be continued until disease progression, unacceptable toxicity, withdrawal of consent, or fulfillment of other protocol-defined discontinuation criteria. Dose interruption or reduction will be permitted for treatment-related adverse events according to the study protocol.

Osimertinib Alone; Osimertinib Plus Primary Tumor Resection

Eligibility Criteria

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

You may qualify if:

• Histologically or cytologically confirmed NSCLC.
• Age ≥18 years.
• AJCC 8th edition stage IV NSCLC.
• EGFR sensitizing mutation limited to exon 19 deletion or exon 21 L858R.
• WHO performance status 0-1. Patients with brain metastases must be conscious; patients with bone metastases must not have irreversible severe events such as severe pathological fracture.
• Disease distribution meeting all of the following criteria:
• no more than 3 involved organs;
• one dominant pulmonary primary lesion;
• the maximal diameter of the dominant pulmonary primary lesion is greater than any single distant metastatic lesion;
• total number of distant metastatic lesions fewer or equal to 10.
• The primary lung tumor is considered resectable by the investigator and thoracic surgeon, with surgery intended for maximal regional control.
• The patient is able to take oral medication and is expected to receive first-line osimertinib induction therapy.
• Major organ function and pulmonary reserve are adequate to tolerate the planned surgery.
• After 12 weeks of protocol-defined osimertinib induction, the patient must have PR or SD by RECIST 1.1 and remain eligible for randomization.
• Subjects may proceed to randomization only if all of the following criteria are met:

You may not qualify if:

• Pathology other than non-small cell lung cancer (NSCLC), or failure to meet the EGFR mutation criteria specified in this study.
• EGFR mutation other than exon 19 deletion or exon 21 L858R.
• Involvement of more than 3 organs by tumor lesions.
• Total number of distant metastatic lesions greater than 10.
• No clearly dominant primary pulmonary lesion, or the maximal diameter of the dominant primary pulmonary lesion is not greater than any individual distant metastatic lesion.
• Diffuse pleural or peritoneal carcinomatosis that cannot be clearly localized and treated with local definitive therapy.
• Progressive disease (PD) on imaging evaluation after 12 weeks of protocol-defined osimertinib induction.
• Judged by the investigator or thoracic surgeon to be no longer suitable for thoracic surgery after induction therapy.
• Any systemic therapy other than the protocol-defined osimertinib induction for the current stage IV NSCLC.
• Any prior EGFR-TKI, chemotherapy, immunotherapy, or other systemic anticancer therapy for the current stage IV NSCLC, except for the protocol-defined osimertinib induction.
• Pregnant, breastfeeding, or planning pregnancy during the study period.
• Any condition that, in the investigator's judgment, makes the subject unsuitable for participation in this study, or highly likely to be unable to comply with the study procedures, restrictions, or requirements.

Sponsors & Collaborators

• National Taiwan University Hospital: lead

Study Sites (1)

National Taiwan University Hospital

Taipei, Taipei City, 100, Taiwan

Location

MeSH Terms

Conditions

Lung Neoplasms; Carcinoma, Non-Small-Cell Lung

Interventions

osimertinib

Condition Hierarchy (Ancestors)

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

Study Officials

• Chong-Jen Yu, MD

  National Taiwan University Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Chong-Jen Yu, MD

CONTACT

+886-2-2322-0322; jefferycjyu@ntu.edu.tw

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: Because one treatment group undergoes surgery, participants and treating investigators will be aware of treatment assignment.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: National Taiwan University Hospital

Model Details: All participants will receive 12 weeks of first-line osimertinib induction therapy before randomization. Participants with partial response or stable disease who remain eligible for surgery will be randomized in a 1:1 ratio to continue osimertinib alone or to undergo primary lung tumor resection followed by resumption of osimertinib.

Study Record Dates

• First Submitted: July 23, 2026
• First Posted: July 31, 2026
• Study Start: August 1, 2026
• Primary Completion (Estimated): August 1, 2031
• Study Completion (Estimated): August 1, 2031
• Last Updated: July 31, 2026

Record last verified: 2026-07

Locations

TW (1)