Local Ablative Therapy to Oligoresidual Metastasis in EGFR Mutated Non-small Cell Lung Cancer

ATOM2: A Randomized Phase II Trial on Ablative Therapy to Oligoresidual Metastasis in EGFR Mutated Non-small Cell Lung Cancer After Osimertinib Treatment

This is an open-label, multicentre, randomized phase II clinical trial. Patients with stage IV (AJCC 9th edition) non-small cell lung cancer (NSCLC) harboring EGFR exon 19 deletion or exon 21 L858R mutation, who had less than or equal to 3 active oligoresidual cancer sites amenable to local ablative therapy (LAT) (as determined by physician) after 3-6 months of firstline osimertinib treatment, are eligible. Subjects will be randomized 1:1 to osimertinib with or without LAT.

Study Overview

• Status: Recruiting
• Conditions: Lung Cancer (NSCLC)
• Intervention / Treatment: Radiation: Local ablative therapy; Drug: Osimertinib alone

• Study Type: Interventional
• Enrollment (Estimated): 64
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Molly SC LI, MBBS, MRCP; Phone Number: 3505 1042; Email: molly@clo.cuhk.edu.hk

Study Locations

• Hong Kong
  • Hong Kong, Hong Kong
    • Recruiting
    • Department of Clinical Oncology, Prince of Wales Hospital
    • Contact: Molly SC LI, MBBS, MRCP; Phone Number: 3505 1042; Email: molly@clo.cuhk.edu.hk
    • Principal Investigator: Molly SC LI, MBBS, MRCP

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 18 years of age or older and able to understand and give written informed consent
• Pathologically proven non-small cell lung cancer
• Positive for EGFR exon 19 deletion or EGFR exon 21 L858R mutation (either by tissue or plasma testing)
• Stage IV disease
• Receive first line osimertinib monotherapy for stage IV disease
• Undergo a PET-CT scan after 12-24 weeks of initiation of osimertinib treatment, with no evidence of disease progression, and less than or equal to 3 active disease sites (including primary tumour) amenable to local ablative therapy, as determined by investigator
• At least one brain imaging (CT Brain or MRI Brain with contrast, preferably MRI Brain), either at time of diagnosis or while on osimertinib treatment but before randomization, to document CNS status for stratification. Patients with asymptomatic CNS metastases are eligible. For patients with brain metastases diagnosed at baseline, follow up brain imaging is recommended before randomization.
• Patients with history of palliative radiotherapy are eligible
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1
• Adequate haematological values: haemoglobin ≥9.0g/dL, absolute neutreophil count ≥1.0 x 109/L, platelet count ≥100 x 109/L
• Adequate hepatic function: bilirubin ≤1.5 x ULN, AST/ALT ≤2.5 x ULN
• Adequate renal function: creatinine clearance ≥30ml/min, according to the formula of Cockcroft-Gault equation
• Willing and able to comply with the requirements and restrictions in this protocol

Exclusion Criteria:

• Previous or concomitant malignancy within 5 years prior registration with the exception of adequately treated localized non-melanoma skin cancer or cervical cancer in situ.
• Mixed SCLC and NSCLC histology
• Positive pregnancy test
• Contraindication to radiotherapy
• Any serious underlying medical, psychiatric, psychological, familial condition that in the judgement of the investigator, that may interfere with planned staging, treatment and follow up, affect patient compliance, or place the patient at high risk from treatment related complications

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Radiotherapy arm; Continue osimertinib as per standard of care (40mg or 80mg daily).; Undergo radiotherapy to 1-3 disease sites as determined by the investigator.	Radiation: Local ablative therapy; Local ablative therapy (LAT) will be given in the form of stereotactic body radiotherapy (SBRT) or hypofractionated radiotherapy. LAT should be started within 90 days from the screening PET-CT scan.
Active Comparator: Control arm; Continue osimertinib as per standard of care (40mg or 80mg daily)	Drug: Osimertinib alone; Continue osimertinib as per standard of care (40mg or 80mg daily)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
18 month progression-free survival rate (PFS) in per-protocol population as determined by investigator.	up to 2 years

Secondary Outcome Measures

Outcome Measure	Time Frame
Overall survival (OS)	2 years
Safety and tolerability reflected by number of participants with treatment related adverse events as assessed by CTCAE v5.0, number of participants with SAE	2 years
Time to treatment failure (TTF), defined as the time period between osimertinib initiation and cessation or death	2 years
Site of tumour progression at disease progression	2 years

Collaborators and Investigators

• Sponsor: Chinese University of Hong Kong

Study record dates

Study Major Dates

• Study Start (Actual): February 11, 2026
• Primary Completion (Estimated): March 3, 2029
• Study Completion (Estimated): March 3, 2030

Study Registration Dates

• First Submitted: December 17, 2025
• First Submitted That Met QC Criteria: January 27, 2026
• First Posted (Actual): January 30, 2026

Study Record Updates

• Last Update Posted (Actual): February 12, 2026
• Last Update Submitted That Met QC Criteria: February 11, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; osimertinib
• Other Study ID Numbers: LUN126

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No