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

Conditions

• Lung Neoplasms, Non-Small Cell Lung Cancer

Eligibility Criteria

Sex

ALL

Age

18 Years - N/A

Healthy Volunteers

Not accepted

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 — 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.

Study Details

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.

Key Dates

First listed

Jul 31, 2026

Start date

Aug 1, 2026

Status verified

Aug 2026

Primary completion

Aug 1, 2031

Completion

Aug 1, 2031

Study Design

Enrollment

154 participants (estimated)

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Arms

• Active Comparator: Osimertinib Alone
  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.
• Experimental: Osimertinib Plus Primary Tumor Resection
  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.

Primary Outcome Measure

Progression-Free Survival [ Time Frame: From randomization to disease progression or death, assessed up to 24 months after randomization. ]

Central Contacts

• Chong-Jen Yu, MD
  +886-2-2322-0322
  [email protected]