198TiP DEDALUS trial: A single-arm, phase II, multi-center study of chemo-immunotherapy followed by hypo-fractionated RT and maintenance immunotherapy in patients with unresectable stage III NSCLC

PACIFIC regimen is the gold standard for patients with unresectable locally advanced Non-Small Cell Lung Cancer (NSCLC). Moving forward on developing best treatment combination, this study aims to assess safety and efficacy of a induction chemo-immunotherapy followed by de-intensified, hypo-fractionated RT given concurrently Durvalumab maintenance in unresectable, stage III NSCLC. Dedalus trial phase 2, open-label, single-arm, multi-center, Italian designed determine reduced-dose radiotherapy immunotherapy fixed dose monotherapy. 45 will be enrolled from March 2022 2024. Patients meet following major criteria could included: NSCLC III, PD-L1 all comers, judged ineligible cCRT thoracic multidisciplinary board then candidate sCRT. After three cycles Cisplatin/Carboplatin (AUC5) plus Etoposide every weeks, responders receiving (45 Gy over 3 weeks) Durvalumab, up 12 months or progression. Primary endpoint safety, defined incidence grade 3-4 possibly related adverse events within 6 initiation treatment. Secondary objectives are PFS OS (median months) quality life (investigated through EORTC QLQ-C30 LC13 questionnaires). Ancillary studies consist radiomic molecular analyses: correlation signatures extracted form baseline post-RT TC-scans PFS; alterations detected tumor tissue specimens obtained at diagnosis monitored ctDNA plasma trough liquid biopsies different time-points (at baseline, after progression). First patient was 2022; time submission, eight included trial. NCT05128630. Fondazione IRCCS Policlinico San Matteo, Pavia, Italy. AstraZeneca.