Local ablative therapy added to osimertinib for EGFR‑mutant metastatic NSCLC with few remaining tumor sites

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

This trial tests whether adding local ablative therapy to ongoing osimertinib helps people with EGFR exon 19 or exon 21 L858R mutated stage IV non‑small cell lung cancer who have three or fewer active tumor sites after initial treatment.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 64 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Chinese University of Hong Kong (Academic / other)
• Drugs / interventions: osimertinib
• Locations: 1 site (Hong Kong)
• Trial ID: NCT07379476 on ClinicalTrials.gov

What this trial studies

This is an open‑label, randomized phase II trial enrolling patients with stage IV NSCLC harboring EGFR exon 19 deletion or exon 21 L858R who have ≤3 active disease sites after 12–24 weeks of first‑line osimertinib. After confirmation of eligibility including PET‑CT and brain imaging, participants are randomized 1:1 to continue osimertinib alone or receive local ablative therapy (such as stereotactic radiotherapy or other physician‑selected LAT) to all oligoresidual sites in addition to osimertinib. The trial is multicenter and follows patients for disease control and survival outcomes, with CNS status accounted for in stratification. Treatment decisions about the type and timing of local ablative therapy are made by the treating physicians based on lesion location and patient factors.

Who should consider this trial

Good fit: Adults (≥18) with pathologically confirmed stage IV NSCLC harboring EGFR exon 19 deletion or exon 21 L858R who have received first‑line osimertinib for 12–24 weeks with no progression and have ≤3 active sites amenable to local ablative therapy are ideal candidates.

Not a fit: Patients with more than three active metastatic sites, documented progression on osimertinib, EGFR mutations other than exon 19 deletion or exon 21 L858R, symptomatic uncontrolled brain metastases, or lesions not suitable for local ablative therapy are unlikely to benefit from this approach.

Why it matters

Potential benefit: If successful, adding local ablative therapy could prolong disease control and delay progression for patients with limited residual metastatic sites while they remain on targeted osimertinib therapy.

How similar studies have performed: Prior randomized and phase II studies in oligometastatic NSCLC and smaller series combining local consolidative therapy with EGFR tyrosine kinase inhibitors have shown promising improvements in progression‑free survival, but definitive, large‑scale evidence in this specific setting is still limited.

Eligibility criteria

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

Where this trial is running

Hong Kong

• Department of Clinical Oncology, Prince of Wales Hospital — Hong Kong, Hong Kong (Recruiting)

Study contacts

• Study coordinator: Molly SC LI, MBBS, MRCP

Conditions Lung Cancer