Current Trial Report|Articles in Press

Rationale and Design of a Single-Arm, Phase 2, Multi-Center Study of Chemo-Immunotherapy Followed by Hypo-Fractionated RT and Maintenance Immunotherapy in Patients With Unresectable Stage III NSCLC: The DEDALUS Trial

Published:January 20, 2023DOI:



      This single-arm, phase 2, multi-center, study aims to assess the safety and efficacy of a regimen of induction chemo-immunotherapy followed by de-intensified, hypo-fractionated thoracic radiotherapy (RT) given concurrently with durvalumab and maintenance durvalumab in patients with unresectable, stage III NSCLC.

      Material and methods

      we will enroll 45 patients with unresectable stage III NSCLC, any PD-L1, deemed ineligible for concurrent CRT by a thoracic oncology multidisciplinary team, and candidate to sequential chemoradiation followed by durvalumab.


      Primary endpoint is safety, defined by the incidence of grade 3 and 4 possibly related adverse events (PRAEs) within 6 months from the initiation of treatment. The secondary objectives are PFS and OS (median and 12 months). Ancillary endpoints are molecular response evaluated by cfDNA isolation baseline, after chemo-immuno RT and at progression, and radiomics analysis on CT scans at baseline and before maintenance.


      DEDALUS phase 2 trial explores the safety and efficacy of a novel sequence of chemo-radiation (with de-intensified RT) plus the anti-PD-L1 agent durvalumab in patients with stage III unresectable NSCLC who are candidates to sequential chemoradiation plus maintenance immunotherapy.


      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Clinical Lung Cancer
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Spigel DR
        • Faivre-Finn C
        • Gray JE
        • et al.
        Five-year survival outcomes from the PACIFIC Trial: Durvalumab after Chemoradiotherapy in stage III non-small-cell Lung Cancer.
        J Clin Oncol. 2022; (Feb 20: 40(12):1301-1311)
        • De Ruysscher D
        • Botterweck A
        • Dirx M
        • et al.
        Eligibility for concurrent chemotherapy and radiotherapy of locally advanced lung cancer patients: a prospective, population-based study.
        Ann Oncol. 2009; 20: 98-102
        • Garassino M
        • Faivre-Finn C
        • Mazieres J
        • et al.
        PACIFIC-6: A phase II Study of Durvalumab following sequential chemoradiotherapy in patients with stage III, unresectable NSCLC.
        J Thorac Oncol. 2022 Dec; 17: 1415-1427
        • Goldman JW
        • Dvorkin M
        • Chen Y
        • et al.
        CASPIAN investigators. Durvalumab, with or without tremelimumab, plus platinum-etoposide versus platinum-etoposide alone in first-line treatment of extensive-stage small-cell lung cancer (CASPIAN): updated results from a randomised, controlled, open-label phase 3 trial.
        Lancet Oncol. 2021; 22: 51-65
      1. Forde PM., Spicer J, Provencio T, et al. Neoadjuvant Nivolumab plus Chemotheray in resectable Lung Cancer. N Engl J Med. 2022 May 26;386(21):1973-1985.

        • Bradley JD
        • Paulus R
        • Komaki R
        • et al.
        A randomized phase III comparison of standard-dose (60 Gy) versus high-dose (74 Gy) conformal chemoradiotherapy with or without cetuximab for stage III non-small-cell lung cancer: results on radiation dose in RTOG 0617.
        J Clin Oncol. 2013; 31: 7501
        • Jin JY
        • Hu C
        • Xiao Y
        • Zhang H
        • et al.
        Higher radiation dose to the immune cells correlates with worse tumor control and overall survival in patients with stage III NSCLC: a secondary analysis of RTOG0617.
        Cancers (Basel). 2021; 13: 6193
        • Amini A
        • Lin SH
        • Wei C
        • Allen P
        • Cox JD
        • Komaki R.
        Accelerated hypofractionated radiation therapy compared to conventionally fractionated radiation therapy for the treatment of inoperable non-small cell lung cancer.
        Radiat Oncol. 2012; 7: 33
        • Pollom EL
        • Qian Y
        • Durkee BY
        • et al.
        Hypofractionated intensity-modulated radiotherapy for patients with non-small cell lung cancer.
        Clin Lung Cancer. 2016; 17: 588-594
        • Ladbury CJ
        • Rusthoven CG
        • Camidge DR
        • Kavanagh BD
        • Nath SK.
        Impact of radiation dose to the host immune system on tumor control and survival for stage III non-small cell lung Cancer treated with definitive radiation therapy.
        Int J Radiat Oncol Biol Phys. 2019; 105: 346-355
        • Abravan Azadeh
        • Faivre-Finn Corinne
        • Kennedy Jason
        • McWilliam Alan
        Marcel van Herk. Radiotherapy-Related Lymphopenia affects overall survival in patients with lung Cancer.
        J Thor Oncol. 2020; 5: 1624-1635
        • Banfill K
        • Giuliani M
        • Aznar M
        • et al.
        IASLC advanced radiation technology committee. cardiac toxicity of thoracic radiotherapy: existing evidence and future directions.
        J Thorac Oncol. 2021; 16: 216-227