125P Preliminary analysis on safety of the DEDALUS phase II trial: Induction chemo-durvalumab followed by reduced-dose radiotherapy and maintenance durvalumab for patients with unresectable stage III NSCLC

In this phase II, single-arm study, patients with stage III unresectable NSCLC deemed not eligible for concurrent chemoradiotherapy (CRT) by a MDT are treated with induction chemo-immunotherapy followed by de-intensified, hypo-fractionated radiotherapy (RT) plus durvalumab, followed by durvalumab maintenance. This report presents a pre-planned, interim safety analysis. Patients with tumors with any PD-L1 expression, EGFR/ALK-negative, were eligible. After 3 cycles of CT-durvalumab, responders (SD, CR, PR) received hypo-fractionated thoracic RT (45 Gy over three weeks) with concurrent durvalumab, followed by durvalumab maintenance for up to 12 months or until progression. The primary endpoint was safety, defined as the incidence of possibly related adverse events (PRAES) within the first six months from the first durvalumab dose. Benchmark comparison will be made with PACIFIC-6 safety and efficacy, using identical inclusion/exclusion criteria. The first patient was screened in February 2022. At the time of data extraction, 21 pts were screened, and 20 enrolled across 3 Italian Centers. Baseline features: median age of 71 (51-84 yrs); 11 male, and 9 females. All were smokers, 8 with squamous, and 12 non-squamous histology; 4 stage IIIA, 13 IIIB, 3 IIIC; PD-L1 was negative in 7, 1-49% in 6, and ≥ 50% in 5 (2 not available). Two pts (10%) had grade 3/4 PRAES, during the induction phase (two neutropenia with sepsis), leading to permanent interruption. Two additional pts had grade 3 serious adverse events unrelated to treatment but leading to discontinuation. We observed 5 disease progressions (1 during induction, 2 before RT, 1 post-RT, and 1 during maintenance). Nine pts are still on treatment, without recorded PRAES. Two pts are in follow-up. This preliminary safety analysis supports the feasibility and tolerability of the DEDALUS sequence. The trial will continue enrolling patients, also collecting longitudinal blood samples for ctDNA measurement baseline, after CRT and at progression.