S2972
Late-Breaking
ESTRO 2026
UCLouvain, Brussels, Belgium. 4 Radiation Oncology, Radboud University Medical Center, Nijmegen, Netherlands. 5 Pulmonary medicine, Erasmus MC Cancer Institute, Rotterdam, Netherlands. 6 Respiratory Diseases, University Hospitals KU Leuven, Leuven, Belgium. 7 Radiation Oncology, Iridium Netwerk, University of Antwerp, Antwerp, Antwerp, Belgium. 8 Radiation Oncology (Maastro), Research Institute for Oncology and Reproduction, Maastricht University Medical Center, Maastricht, Netherlands. 9 Radiation Oncology, Cliniques universitaires Saint-Luc; MIRO – IREC Lab, UCLouvain,, Brussels, Belgium. 10 Radiation Oncology, University College London, London, United Kingdom. 11 Experimental and Translational Immunology, Technical University of Denmark, Kongens Lyngby, Denmark. 12 Radiation Oncology, Netherlands Cancer Institute – Antoni van Leeuwenhoek, Amsterdam, Netherlands. 13 Statistics, Maastricht University Medical Center+,, Maastricht, Netherlands. 14 Radiation Oncology, UZ Gasthuisberg, Leuven, Belgium. 15 Precision Medicine, Maastricht university, Maastricht, Netherlands. 16 Radiation Oncology, Ghent University Hospital and Ghent University, Ghent, Belgium. 17 Biotherapeutics, Philochem AG, Otelfingen, Switzerland. 18 Radiation Oncology, Oscar Lambret Comprehensive Cancer Center, Lille, France. 19 Thoracic Oncology, Ghent University Hospital and Ghent University, Ghent, Belgium. 20 Dpt of Pulmonary Diseases, Research Institute for Oncology and Reproduction, Maastricht University Medical Center, Maastricht, Netherlands Purpose/Objective: Patients with stage IV non-small-cell lung cancer (NSCLC) and limited metastatic burden may benefit from local ablative radiotherapy (RT), but durable disease control remains limited. Preclinical work suggests that stereotactic ablative radiotherapy (SABR) can synergise with the tumour-targeted immunocytokine L19-IL2 by enhancing anti-tumour immunity. We report the primary results of ImmunoSABR, a multicentre randomised phase II trial evaluating whether adding L19-IL2 to SABR improves outcomes versus standard of care in stage IV NSCLC with oligometastatic or limited polymetastatic disease. Material/Methods: ImmunoSABR (NCT03705403) was a multicentre, randomised phase II trial in academic centres in the Netherlands, Belgium, Germany, France and the UK. Eligible patients had pathologically confirmed stage IV NSCLC, WHO 0-1, and either oligometastatic (<=5 metastases in <=3 organs) or limited polymetastatic disease (6-10 metastases). Patients were randomly assigned 1:1 using web-based minimisation stratification. Standard of care consisted of guideline- based systemic therapy, with RT permitted according to symptoms in the poly group and SABR
recommended in the oligo group. In the experimental group, patients received SABR to a maximum of five lesions followed within 72 hours by intravenous L19- IL2 on days 1, 3, and 5 every 3 weeks for up to six cycles. The primary endpoint was 1.5-year progression-free survival (PFS). Results: Between 10/01/20 and 31/12/23, a total of 88 of the planned 126 patients were enrolled, 44 to the experimental group and 44 to the control group. The last patient was enrolled in January24. The trial was closed prematurely because of poor accrual related to the COVID-19 pandemic. Baseline characteristics were balanced between the two groups. The probability of PFS survival at 1.5 years was 21.5% (95% CI 11.9-39.0) in the experimental group and 11.4% (95% CI 4.5-28.9) in the control group (log-rank p=0.152, Fig.1). The adjusted hazard ratio for PFS was 0.66 (95% CI 0.40- 1.08; p=0.096). In an exploratory analysis, total tumour burden, quantified by deep learning as the sum of all lesion volumes, was significantly associated with overall survival (log-rank p = 0.010; Fig. 2), whereas the poly- versus oligometastatic grouping was not. Baseline plasma markers of immune activation (e.g., CXCL13, IL7, CD70, CASP8) were associated with improved outcomes in the experimental arm, suggesting greater benefit in “hot” tumours, whereas hypoxia-related plasma biomarkers were associated with reduced benefit.
Conclusion: Because the trial closed early, results must be regarded as hypothesis-generating. However, the favourable PFS trend and acceptable toxicity support further investigation of SABR/L19-IL2 in biomarker- selected patients.
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