A Multicenter Two-arm, Phase II Trial Assessing the Safety and Efficacy of First-line Lazertinib and Locally Ablative Radiotherapy in Patients With Synchronous Oligo-metastatic EGFR-mutant Non-small Cell Lung Cancer (ABLATE, KCSG-LU21-11)

Background: The current standard treatment of advanced non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutation is upfront EGFR targeted therapy. However, patients invariably experience disease progression at primary tumors or metastatic sites. Adding stereotactic body radiation therapy (SBRT) to systemic therapy can improve progression-free survival (PFS) and overall survival (OS). This multicenter, 2-arm, phase II study aims to evaluate the efficacy and safety of lazertinib, a third generation EGFR tyrosine kinase inhibitor, combined with upfront locally ablative radiotherapy in EGFR-mutant NSCLC patients with synchronous oligometastatic disease (ClinicalTrials.gov: NCT05167851). Patients and Methods: Key inclusion criteria are biopsy-proven EGFR-mutated adenocarcinoma with synchronous, oligometastatic (≤5 metastases) NSCLC. Patients will be randomized 1:1 to receive lazertinib or lazertinib + SBRT to the primary tumor and metastatic sites. The primary endpoint is PFS according to RECIST: Response Evaluation Criteria in Solid Tumor version 1.1, and the secondary endpoints are OS, objective response rate, and safety. Results: Patient enrolment began in January 2021 and is ongoing at 7 sites in the Republic of Korea. Conclusion: This trial will provide valuable information on the efficacy and safety of lazertinib in combination with SBRT in patients with synchronous, oligometastatic EGFR-mutant NSCLC.