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

BMC Cancer

卷:20

David Pasquier¹  Crispin Hiley²  Dario Neri³  Sine R. Hadrup⁴  Lizza E. L. Hendriks⁵  Anne-Marie C. Dingemans⁶  Evert J. Van Limbergen⁷  Dirk De Ruysscher⁷  Xavier Geets⁸  Yolande Lievens⁹  Pierre Boisselier¹⁰  Charlotte Billiet¹¹  Monique C. de Jong¹²  Johan Bussink¹³  Franziska Eckert¹⁴  Esther G. C. Troost¹⁵  Christophe Dooms¹⁶  Vincenzo Valentini¹⁷  Amir Abdollahi¹⁸  Giuliano Elia¹⁹  Philippe Lambin²⁰  Cary J. G. Oberije²⁰  Relinde I. Y. Lieverse²⁰  Ludwig J. Dubois²⁰  Ala Yaromina²⁰ 

[1] Academic Department of Radiation Oncology, Oscar Lambret Comprehensive Cancer Center;

[2] Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute;

[3] Department of Chemistry and Applied Biosciences, Institute of Pharmaceutical Sciences, ETH Zurich;

[4] Department of Health Technology, Technical University of Denmark;

[5] Department of Pulmonary Diseases, GROW - School for Oncology and Developmental Biology, Maastricht University Medical Centre;

[6] Department of Pulmonary Medicine, Erasmus MC Rotterdam;

[7] Department of Radiation Oncology (MAASTRO), GROW - School for Oncology and Developmental Biology, Maastricht University Medical Center;

[8] Department of Radiation Oncology, Cliniques Universitaires Saint-Luc, MIRO - IREC Lab, UCL;

[9] Department of Radiation Oncology, Ghent University Hospital and Ghent University;

[10] Department of Radiation Oncology, ICM-Val d’Aurelle, Université de Montpellier;

[11] Department of Radiation Oncology, Iridium Network;

[12] Department of Radiation Oncology, Netherlands Cancer Institute—Antoni van Leeuwenhoek Hospital;

[13] Department of Radiation Oncology, Radboud University Medical Center;

[14] Department of Radiation Oncology, University Hospital and Medical Faculty Tübingen, Eberhard Karls University Tübingen;

[15] Department of Radiotherapy and Radiation Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus at Technische Universität Dresden;

[16] Department of Respiratory Diseases, Respiratory Oncology Unit, University Hospitals KU Leuven;

[17] Dipartimento Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, Fondazione Policlinico Universitario A. Gemelli IRCCS;

[18] Division of Molecular and Translational Radiation Oncology, Department of Radiation Oncology, Heidelberg Faculty of Medicine (MFHD) and Heidelberg University Hospital (UKHD), Heidelberg Ion-Beam Therapy Center (HIT);

[19] Philochem AG;

[20] The D-Lab and The M-Lab, Department of Precision Medicine, GROW - School for Oncology and Developmental Biology, Maastricht University;

关键词: Immunotherapy;    L19-IL2;    Anti-PD-L1;    Anti-PD-1;    Radiotherapy;    SABR;   

DOI  :  10.1186/s12885-020-07055-1

来源: DOAJ

【 摘 要 】

Abstract 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.

【 授权许可】

Unknown