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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

Date

12 Dec 2020

Session

Mini Oral session 2

Presenters

Christophe Le Tourneau

Citation

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

Authors

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
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Resources

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Abstract 63MO

Background

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).

Methods

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.

Results

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.

Conclusions

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

NCT03260023.

Legal entity responsible for the study

Transgene SA.

Funding

Transgene, Merck Serono.

Disclosure

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.

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