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Poster Display session

448 - Predictive markers of immune mediated adverse events and of treatment response in patients treated with durvalumab monotherapy or in combination with tremelimumab (IOPREDI study)


14 Dec 2018


Poster Display session


Aurelien Marabelle


Annals of Oncology (2018) 29 (suppl_10): x1-x10. 10.1093/annonc/mdy493


A. Marabelle1, F. Ghiringhelli2, M. Ayyoub3, E. Tartour4, O. Adotevi5, Y. Loriot6, O. Lambotte7, D. Cupissol8, D. Damotte9, J. Adam10, M. Bonvalet11, B. Petre Lazar12, M. Licour12, N. Chaput13

Author affiliations

  • 1 Drug Development Department, Gustave Roussy, 94805 - Villejuif/FR
  • 2 Oncology, CGFL, 21000 - DIJON/FR
  • 3 Oncopole, IUCT, 31037 - Toulouse/FR
  • 4 Oncology, Hopital European George Pompidou, 75015 - Paris/FR
  • 5 Immunotherapy, UMR1098, 25020 - Besançon/FR
  • 6 Department Of Cancer Medicine, Gustave Roussy, 94805 - Villejuif/FR
  • 7 94, CHU de Bicêtre, 91275 - Le Kremlin Bicetre/FR
  • 8 Medical Oncology, Laboratoire de Radio-Analyse du C.R.L.C., 34298 - Montpellier/FR
  • 9 Pathology, hopital Cochin, 75014 - Paris/FR
  • 10 Pathology, Institut Gustave Roussy, 94800 - Villejuif/FR
  • 11 Inserm, Umr 1015, Gustave Roussy, 94805 - Villejuif/FR
  • 12 Oncology, AstraZeneca, 92400 - Courbevoie/FR
  • 13 Immuno Oncology, Gustave Roussy Institut de Cancérologie, 94805 - Villejuif/FR


Abstract 448


Immune-targeted monoclonal antibodies blocking inhibitory immune checkpoints such as CTLA-4, PD-1 and PD-L1 have shown durable responses in multiple tumour types. These drugs generate a new type of complications in oncology: immune-related adverse events (ImAE). There is no established predictive biomarker to identify patients (pts) who are likely to develop severe ImAE. The hypothesis is that imAEs could result from host related pre-existing factors: Activation of self-reactive T and B cells, genetic predisposition, metabolic factors, enhanced cross reactivity between cancer cells, healthy cells and resident microbiota flora, and co-morbidity, concomitant treatments and patients’ environment. Response to immunotherapy could also be associated with pre-existing factors and tumor microenvironment features.

Trial design

The study is a French ancillary study of a phase 3b, open-Label, multi-Centre, safety study of fixed-dose durvalumab + tremelimumab combination therapy or durvalumab monotherapy in advanced solid malignancies (STRONG) (NCT03084471). By collecting additional blood and tumour samples (table 1) the aim of this ancillary study is to define the immune phenotype, microbiome analysis of patients prior to an immunotherapy and who are subsequently developing an imAE or who achieve response to identify and characterize predictive factors of the toxicity and of efficacy. For both efficacy and safety objectives, respectively 85 and 300 patients will be required. The STRONG study currently includes pts with an urothelial and nonurothelial carcinoma of the urinary tract, treated with durvalumab as single agent at progression on or after of chemotherapy. As of July 2018, the IOPREDI ancillary study has been opened, 18 centres have been activated and 9 patients have been enrolled. Table 1 a) definition of AESI see section 6, b) only at baseline for polymorphisms, c) within 72 hours prior to the first treatment administration d) within 72 hours of occurrence of AESI.

Editorial acknowledgement

Clinical trial identification

EudraCT: 2016-005068-33.

Legal entity responsible for the study





A. Marabelle, F. Ghiringhelli: Honoraria for scientific boards: AstraZeneca. M. Ayyoub, O. Adotevi, Y. Loriot, O. Lambotte: Honoraria for advisory boards: AstraZeneca. D. Cupissol, D. Damotte, N. Chaput: Honoraria for scientific committee meetings: AstraZeneca. J. Adam: Honoraria for advisory boards: AstraZeneca. B. Petre Lazar, M. Licour: Employee of AstraZeneca. All other authors have declared no conflicts of interest.Table: 30TiP

VisitScreeningTreatment period BaselineTreatment period C2D1Treatment period In case of AESIa ≥grade 2Treatment period C3D1At progression
WeekWeeks -4 to Week -1Week 0Week 4Week 8
Autoantibodies Polymorphisms (serum)XbXXX
Cytokines and soluble factors / Metabolic factors (plasma)XXX
Cell-free DNAXX
Immune cells RNA (whole blood)X
Hb1Ac, glycaemia, T3 and T4XXX
Stools sampleX cd
Telomerase, commensal and NYESO-1 T cells specific immune response (frozen PBMC)XXXXX
Epithelial mesenchymal transition (tumor sample)X

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