Author of

• 35146

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  P17 - Locoregional and Oligometastatic Disease - Biomarkers (ID 127)

  • Event: WCLC 2020
  • Type: Posters
  • Track: Locoregional and Oligometastatic Disease
  • Presentations: 1
  • Moderators:
  • Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall

  • 35150

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    P17.02 - Durvalumab After chemoRadioTherapy (DART) for NSCLC Patients – a Phase II Translational and Biomarker Study (ID 3645)

    00:00 - 00:00  |  Presenting Author(s): Vilde Drageset Haakensen
    • Abstract
    • Slides

    Introduction
    

    Lung cancer is the most common cause of cancer-related deaths world-wide. Approximately one third of patients with non–small-cell lung cancer (NSCLC) are diagnosed with locally advanced disease (stage III) at diagnosis¹, for whom the standard of care is platinum-based doublet chemotherapy concurrent with radiotherapy resulting in 5-year survival of 15-20%. In the PACIFIC study, a superior outcome was observed for patients receiving the checkpoint inhibitor durvalumab after chemoradiation². The median progression-free survival from randomization was 16.8 month with durvalumab versus 5.6 months with placebo (p<0.001). The benefit was found in the intention to treat-population, and PD-L1 expression was not a good predictive biomarker. Despite impressive results, many patients relapsed, and more knowledge of the biology underlying responses and resistance is needed. Durvalumab is approved by the FDA for patients regardless of PD-L1 status, while EMA limited the indication to patients whose tumours harbour PD-L1 expression of ≥1%.

    Methods
    

    This is an investigator initiated, multi-centre phase II translational study. A total of 100 stage III NSCLC patients not progressing after chemoradiotherapy will be included from the Nordic and Baltic countries, 50 PD-L1 negative and 50 PD-L1 positive patients. Astra Zeneca provides durvalumab for all patients. The DART trial aims to identify prognostic and predictive biomarkers which may be used to identify patients who would benefit from durvalumab after chemoradiation. Our hypothesis is that the immunological microenvironment in the tumour influences response. Tumour biopsies will be collected before treatment, after chemoradiation and at progression. Blood and stool samples will be collected and images will be performed before and during treatment as well as during follow-up. The analyses planned are described below linked to the study objectives

    Primary objectives:

    To investigate the immunological response, tumour development (if present) and dynamics in the tumour micro-environment and in circulation. This includes the following:
    - Evaluation of immune cell infiltration in the primary tumour and in the relapse tumour (if present)
    - Evaluation of circulating biomarkers related to tumour (ctDNA) and host response (immune cells)
    - Evaluations of genomic characteristics of the primary tumour and the relapse (if present)

    To investigate tumour mutational burden in tumour tissue and blood samples, as predictors for clinical response

    To evaluate imaging protocols for response prediction. PET-CT will be done for screening, after chemoradiation and after 12 months.

    To investigate potential changes in gut microbiota in serial samples from patients treated with durvalumab and investigate whether microbiota profile prior to, or dynamic changes during treatment can predict clinical outcome

    Secondary objectives:

    To evaluate toxicity and quality of life in lung cancer patients receiving PDL1-inhibitor after chemoradiotherapy

    To evaluate progression-free survival and overall survival

    References

    1. Aupérin A, Le Péchoux C, Rolland E, et al. Meta-analysis of concomitant versus sequential radiochemotherapy in locally advanced non-small-cell lung cancer. J Clin Oncol. 2010;28(13):2181-2190.

    2. Antonia SJ, Villegas A, Daniel D, et al. Overall Survival with Durvalumab after Chemoradiotherapy in Stage III NSCLC. N Engl J Med. 2018

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