Oops, you're using an old version of your browser so some of the features on this page may not be displaying properly.

MINIMAL Requirements: Google Chrome 24+Mozilla Firefox 20+Internet Explorer 11Opera 15–18Apple Safari 7SeaMonkey 2.15-2.23

Mini Oral session 2

63MO - TG4001 therapeutic vaccination combined with PD-L1 blocker avelumab remodels the tumor microenvironement (TME) and drives antitumor responses in human papillomavirus (HPV)+ malignancies


12 Dec 2020


Mini Oral session 2




Christophe Le Tourneau


Annals of Oncology (2020) 31 (suppl_7): S1441-S1451. 10.1016/annonc/annonc392


C. Le Tourneau1, P. Cassier2, F. Rolland3, S. Salas4, J. Limacher5

Author affiliations

  • 1 Department Of Drug Development And Innovation (d3i), Institut Curie, 75005 - Paris/FR
  • 2 Centre Léon Bérard, Lyon/FR
  • 3 Institut de Cancérologie de l’Ouest, Saint Herblain/FR
  • 4 AP-HM, Marseille/FR
  • 5 Hôpitaux Civils de Colmar, Colmar/FR


Login to access the resources on OncologyPRO.

Abstract 63MO


Immune rejection of tumors is contingent to the development of a specific immune response and presence of a favorable TME. We aimed to evaluate the immune priming effect of TG4001, an HPV E6/E7 vaccine based on a recombinant Modified Vaccinia Ankara combined with avelumab, an anti-PD-L1 monoclonal antibody, in HPV+ cancers (NCT03260023).


34 patients (pts) with recurrent/ metastatic HPV16+ anal (15), oropharyngeal (8), cervical (6) or vulvar/vaginal (5) cancer were administered 5·107 pfu SC weekly for 6 weeks (wks), every 2 wks up to month 6, and then every 12 wks in combination with avelumab IV at 10mg/kg every 2 wks. Tissue and PBMC samples were collected at baseline and day (D) 43. T cell responses against HPV antigens were measured using ex-vivo IFNγ-ELISPOT on PBMCs; PD-L1 expression and CD3 and CD8+infiltrate were evaluated by immunostaining of tumor, and changes in gene expression were measured using nanostring.


7 pts achieved partial response and 1 achieved complete response according to RECIST 1.1. 7/11 pts evaluable for ELISPOT developed reactive T cells against E6, E7 or both after vaccination. The patient with complete response had an intense T cell response against E6 and E7 at D43. Reanalysis of this patient after 6 months showed that the T cell response was maintained, consistent with sustained disease control. At baseline, higher level of PD-L1 expression was seen in clinical responders vs. non-responders as well as higher CD3 (median: 470 vs. 200/mm2) and CD8 cell (median: 238 vs 92 /mm2) infiltrates. Infiltrates tended to increase during treatment and, at day 43, were accompanied by strong changes of the tumor transcriptomic profile, involving increase in expression of effector T cell activation cascades such as CD3G, IL21R and IFNG (respectively, 13-fold, 17-fold and 9-fold versus baseline). The Immunosign gene signature was applied as an index of “cold” or “hot” TME profile. 57% of pts had “hot” TME profile at baseline versus 100% at D43.


TG4001 and PD-L1 blockade with avelumab led to the development of specific immunity and TME transformations in HPV+ cancer pts potentially leading to clinical benefit.

Clinical trial identification


Legal entity responsible for the study

Transgene SA.


Transgene, Merck Serono.


C. Le Tourneau: Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: MSD; Advisory/Consultancy: BMS; Advisory/Consultancy: Celgene; Advisory/Consultancy: GSK; Advisory/Consultancy: Merck Serono; Advisory/Consultancy: Rakuten; Advisory/Consultancy: Nanobiotix; Advisory/Consultancy: Roche. P. Cassier: Honoraria (self), Research grant/Funding (institution), Travel/Accommodation/Expenses: Novartis; Honoraria (self), Research grant/Funding (self), Travel/Accommodation/Expenses: Roche/Genentech; Honoraria (self), Travel/Accommodation/Expenses: Amgen; Honoraria (self), Research grant/Funding (institution): AstraZeneca; Honoraria (self), Research grant/Funding (institution), Travel/Accommodation/Expenses: Merck Serono; Research grant/Funding (institution): Lilly; Research grant/Funding (institution): Blueprint Medicines; Research grant/Funding (institution), Travel/Accommodation/Expenses: Bayer; Research grant/Funding (institution): Celgene; Research grant/Funding (institution): Plexxikon; Research grant/Funding (institution): Abbvie; Research grant/Funding (institution), Travel/Accommodation/Expenses: BMS; Research grant/Funding (institution), Travel/Accommodation/Expenses: MSD; Research grant/Funding (institution): Taiho Pharmaceutical; Research grant/Funding (institution): Toray Industries; Research grant/Funding (institution): Transgene; Research grant/Funding (institution): Loxo; Research grant/Funding (institution): GSK; Research grant/Funding (institution): Innate Pharma; Research grant/Funding (institution): Janssen. F. Rolland: Advisory/Consultancy: Pfizer; Advisory/Consultancy: BMS; Advisory/Consultancy: Ipsen; Advisory/Consultancy: Merck Serono; Advisory/Consultancy: MSD. J-M. Limacher: Honoraria (self), Advisory/Consultancy: AstraZeneca; Shareholder/Stockholder/Stock options: Odimma SA. A. Tavernaro: Shareholder/Stockholder/Stock options, Full/Part-time employment: Transgene. H. Makhloufi: Full/Part-time employment: Transgene. K. Bendjama: Full/Part-time employment: Transgene. J-P. Delord: Advisory/Consultancy: Novartis; Advisory/Consultancy, Research grant/Funding (institution): Roche/Genentech; Advisory/Consultancy, Research grant/Funding (institution): BMS; Advisory/Consultancy, Research grant/Funding (institution): MSD. All other authors have declared no conflicts of interest.

This site uses cookies. Some of these cookies are essential, while others help us improve your experience by providing insights into how the site is being used.

For more detailed information on the cookies we use, please check our Privacy Policy.

Customise settings
  • Necessary cookies enable core functionality. The website cannot function properly without these cookies, and you can only disable them by changing your browser preferences.