About 50% of non-small cell lung cancer (NSCLC) patients have metastatic disease at initial diagnosis, which limits their treatment options and, consequently, the 5-year survival rate (15%). Immune checkpoint inhibitors (ICI), either alone or in combination with chemotherapy, have become standard of care (SOC) for most good performance status patients. However, most patients will not obtain long-term benefit, and new treatment strategies are therefore still needed. Before this project, we demonstrated clinical safety of the tumour-selective immunocytokine L19-IL2, consisting of the anti-EDB scFv L19 antibody coupled to IL2, combined with (stereotactic ablative) radiotherapy (RT).
Within this randomized phase II ImmunoSABR trial, the combination of RT with or without the immunocytokine L19-IL2 with or without ICI has been tested as 1st, 2nd or 3rd line treatment in stage IV NSCLC patients. This bi-modal and triple treatment approach was based on the direct cytotoxic effect of radiotherapy, the tumour selective immunocytokine L19-IL2, the abscopal effect observed distant from the irradiated metastatic site(s), and the memory effect.
The multicentric, randomised controlled open-label phase II clinical trial (NCT03705403) was carried out to test the hypothesis that the combination of RT and L19-IL2 increases the progression free survival (PFS) in patients with limited metastatic NSCLC.
ImmunoSABR’s consortium consists of 14 participating centres located in 6 countries. Primary endpoint was PFS at 1.5 years based, and secondary endpoints were overall survival, toxicity, quality of life and abscopal response. Associative biomarker studies, blood and tumour cell immune monitoring, CT-based radiomics, stool collection, iRECIST, and tumour growth rate have been performed.
Patients were stratified according to their metastatic load (oligo-metastatic: up to 5, or poly-metastatic: 6 to 10 metastases). Patients have been randomised by minimisation to the experimental (E-arm) or the control arm (C-arm). The C-arm received SOC, according to the local protocol. E-arm oligo-metastatic patients received RT to all lesions followed by L19-IL2 therapy; radiotherapy for poly-metastatic patients consisted of irradiation of at least one (symptomatic) to a maximum of 5 lesions (including ICI in both arms if this is the SOC).
