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


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

Lieverse, R.; Van, L. E.; Oberije, C.; Troost, E. G. C.; Hadrup, S.; Dingemans, A.; Hendriks, L.; Eckert, F.; Hiley, C.; Dooms, C.; Lievens, Y.; De, J. M.; Hendriks, L.; Bussink, J.; Geets, X.; Valentini, V.; Elia, G.; Nerio, D.; Billiet, C.; Abdollahi, A.; Pasquier, D.; Boisselier, P.; Yaromina, A.; De, R. D.; Dubois, L.; Lambin, P.

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. We previously 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 (SABR). Within this phase II ImmunoSABR trial, 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. This bi-modal and triple 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.
This investigator initiated, multicentric, randomised controlled open-label phase II clinical trial (NCT03705403) will test the hypothesis that the combination of SABR and L19-IL2 increases the progression free survival (PFS) in patients with limited metastatic NSCLC. Patients will be stratified according to their metastatic load (oligo-metastatic: up to 5, or poly-metastatic: 6 to 10 metastases). Patients will be randomised by minimisation to the experimental (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 at least one (symptomatic) to a maximum of 5 lesions (including ICI in both arms if this is the SOC). ImmunoSABR consists of 14 participating centres located in 6 countries. 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, blood and tumour cell immune monitoring, CT-based radiomics, stool collection, iRECIST, and tumour growth rate will be performed. The first results are expected end 2023.

Keywords: Immunotherapy; L19-IL2; anti-PDL1; anti-PD1; radiotherapy; SABR; phase 2; NSCLC; stage IV; multicentre

  • Open Access Logo BMC Cancer 20(2020), 557

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Publ.-Id: 31064