Journal Article

Stereotactic ablative body radiotherapy (SABR) combined with immunotherapy (L19-IL2) versus standard of care in stage IV NSCLC patients, ImmunoSABR: a multicentre, randomised controlled open-label phase II trial

Lieverse, Relinde I. Y., Dooms, Christophe, Valentini, Vincenzo, Neri, Dario, Dingemans, Anne-Marie C., Lievens, Yolande, Pasquier, David, Lambin, Philippe, Troost, Esther G. C., De Ruysscher, Dirk, Hadrup, Sine R., Eckert, Franziska, Geets, Xavier, Boisselier, Pierre, Dubois, Ludwig J., Abdollahi, Amir, Oberije, Cary J. G., Van Limbergen, Evert J., Elia, Giuliano, Billiet, Charlotte, Hendriks, Lizza E. L., Yaromina, Ala, de Jong, Monique C., Hiley, Crispin, Bussink, Johan

2020

Overview

Background 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 needed. We previously demonstrated clinical safety of the tumour-selective immunocytokine L19-IL2, consisting of the anti-ED-B scFv L19 antibody coupled to IL2, combined with stereotactic ablative radiotherapy (SABR). Methods This investigator-initiated, multicentric, randomised controlled open-label phase II clinical trial will test the hypothesis that the combination of SABR and L19-IL2 increases progression free survival (PFS) in patients with limited metastatic NSCLC. One hundred twenty-six patients will be stratified according to their metastatic load (oligo-metastatic: ≤5 or poly-metastatic: 6 to 10) and randomised to the experimental-arm (E-arm) or the control-arm (C-arm). The C-arm will receive SOC, according to the local protocol. E-arm oligo-metastatic patients will receive SABR to all lesions followed by L19-IL2 therapy; radiotherapy for poly-metastatic patients consists of irradiation of one (symptomatic) to a maximum of 5 lesions (including ICI in both arms if this is the SOC). The accrual period will be 2.5-years, starting after the first centre is initiated and active. Primary endpoint is PFS at 1.5-years based on blinded radiological review, and secondary endpoints are overall survival, toxicity, quality of life and abscopal response. Associative biomarker studies, immune monitoring, CT-based radiomics, stool collection, iRECIST and tumour growth rate will be performed. Discussion The combination of SABR with or without ICI and the immunocytokine L19-IL2 will be tested as 1st, 2nd or 3rd line treatment in stage IV NSCLC patients in 14 centres located in 6 countries. This bimodal and trimodal treatment approach is 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 first results are expected end 2023. Trial registration ImmunoSABR Protocol Code: NL67629.068.18; EudraCT: 2018–002583-11 ; Clinicaltrials.gov: NCT03705403 ; ISRCTN ID: ISRCTN49817477 ; Date of registration: 03-April-2019.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Adult / Anti-PD-1 / Anti-PD-L1 / Antibodies / Biomedical and Life Sciences / Biomedicine / Cancer metastasis / Cancer patients / Cancer Research / Cancer therapies / Carcinoma, Non-Small-Cell Lung - mortality / Carcinoma, Non-Small-Cell Lung - secondary / Carcinoma, Non-Small-Cell Lung - therapy / Care and treatment / Chemoradiotherapy - adverse effects / Chemoradiotherapy - methods / Chemotherapy / Clinical trials / Clinical Trials, Phase II as Topic / Cytokines / Cytotoxicity / Female / Growth rate / Health Promotion and Disease Prevention / Humans / Immune checkpoint inhibitors / Immune system / Immunotherapy / Interleukin 2 / Kinases / L19-IL2 / Lung cancer / Lung Neoplasms - mortality / Lung Neoplasms - pathology / Lung Neoplasms - therapy / Male / Medical and radiation oncology / Medicine/Public Health / Metastases / Metastasis / Middle Aged / Multicenter Studies as Topic / Non-small cell lung cancer / Non-small cell lung carcinoma / Oncology / Patients / Progression-Free Survival / Quality of Life / Radiation therapy / Radiomics / Radiosurgery - adverse effects / Radiosurgery - methods / Radiotherapy / Randomized Controlled Trials as Topic / Recombinant Fusion Proteins - administration & dosage / Recombinant Fusion Proteins - adverse effects / Response Evaluation Criteria in Solid Tumors / SABR / Small cell lung carcinoma / Standard of Care / Study Protocol / Surgical Oncology / Tumors