Combining immunotherapy with an epidrug in squamous cell carcinomas of different locations: rationale and design of the PEVO basket trial.

Apr 19, 2021

Contributor: E de Guillebon,M Jimenez,L Mazzarella,F Betsou,P Stadler,I Peták,E Jeannot,L Chanas,N Servant,G Marret,B A Duso,F Legrand,K N Kornerup,S H Bernhart,G Balogh,R Dóczi,P Filotás,G Curigliano,I Bièche,J Guérin,A Dirner,C Neuzillet,N Girard,E Borcoman,L Larbi Chérif,P Tresca,D B Roufai,C Dupain,S Scholl,F André,X Fernandez,T Filleron,M Kamal,C Le Tourneau

Combining immunotherapy with an epidrug in squamous cell carcinomas of different locations: rationale and design of the PEVO basket trial.

Squamous cell carcinomas (SCCs) are among the most frequent solid tumors in humans. SCCs, related or not to the human papillomavirus, share common molecular features. Immunotherapies, and specifically immune checkpoint inhibitors, have been shown to improve overall survival in multiple cancer types, including SCCs. However, only a minority of patients experience a durable response with immunotherapy. Epigenetic modulation plays a major role in escaping tumor immunosurveillance and confers resistance to immune checkpoint inhibitors. Preclinical evidence suggests that modulating the epigenome might improve the efficacy of immunotherapy. We herein review the preclinical and the clinical rationale for combining immunotherapy with an epidrug, and detail the design of PEVOsq, a basket clinical trial combining pembrolizumab with vorinostat, a histone deacetylase inhibitor, in patients with SCCs of different locations. Sequential blood and tumor sampling will be collected in order to identify predictive and pharmacodynamics biomarkers of efficacy of the combination. We also present how clinical and biological data will be managed with the aim to enable the development of a prospective integrative platform to allow secure and controlled access to the project data as well as further exploitations.
Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.

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About The Expert

E de Guillebon

Department of Drug Development and Innovation (D3i), Institut Curie, Paris, France; Inserm U932 Research Unit – Immunite et cancer, Paris, France.

M Jimenez

Unicancer, Paris, France.

L Mazzarella

Department of Experimental Oncology, European Institute of Oncology – IRCCS, Milan, Italy; Division of Innovative Therapies, European Institute of Oncology – IRCCS, Milan, Italy.

F Betsou

Integrated Biobank of Luxembourg, Dudelange, Luxembourg.

P Stadler

Bioinformatics Group, Department of Computer, University of Leipzig, Leipzig, Germany.

I Peták

Oncompass Medicine Ltd, Budapest, Hungary; Department of Pharmacology and Pharmacotherapy, Semmelweis University, Budapest, Hungary; Department of Pharmaceutical Sciences, University of Illinois at Chicago, Chicago, USA.

E Jeannot

Department of Genetics, Institut Curie, Paris, France; Department of Pathology, Institut Curie, Paris, France.

L Chanas

Data Direction, Institut Curie, Paris, France.

N Servant

Inserm U900 Research Unit, Saint Cloud, France.

G Marret

Department of Drug Development and Innovation (D3i), Institut Curie, Paris, France.

B A Duso

Department of Experimental Oncology, European Institute of Oncology – IRCCS, Milan, Italy.

F Legrand

Unicancer, Paris, France.

K N Kornerup

Integrated Biobank of Luxembourg, Dudelange, Luxembourg.

S H Bernhart

Bioinformatics Group, Department of Computer, University of Leipzig, Leipzig, Germany.

G Balogh

Bioinformatics Group, Department of Computer, University of Leipzig, Leipzig, Germany.

R Dóczi

Oncompass Medicine Ltd, Budapest, Hungary.

P Filotás

Oncompass Medicine Ltd, Budapest, Hungary.

G Curigliano

Division of Innovative Therapies, European Institute of Oncology – IRCCS, Milan, Italy; Department of Pharmacology and Pharmacotherapy, Semmelweis University, Budapest, Hungary; University of Milano, Milan, Italy.

I Bièche

Department of Genetics, Institut Curie, Paris, France.

J Guérin

Data Direction, Institut Curie, Paris, France.

A Dirner

Oncompass Medicine Ltd, Budapest, Hungary.

C Neuzillet

Department of Medical Oncology, Institut Curie, Paris, France; Paris-Saclay University, Paris, France.

N Girard

Department of Medical Oncology, Institut Curie, Paris, France; Paris-Saclay University, Paris, France.

E Borcoman

Department of Drug Development and Innovation (D3i), Institut Curie, Paris, France.

L Larbi Chérif

Department of Drug Development and Innovation (D3i), Institut Curie, Paris, France.

P Tresca

Department of Drug Development and Innovation (D3i), Institut Curie, Paris, France.

D B Roufai

Department of Drug Development and Innovation (D3i), Institut Curie, Paris, France.

C Dupain

Department of Drug Development and Innovation (D3i), Institut Curie, Paris, France.

S Scholl

Department of Drug Development and Innovation (D3i), Institut Curie, Paris, France.

F André

Department of Medical Oncology, Gustave Roussy, Villejuif; INSERM, Gustave Roussy Cancer Campus, UMR981, Villejuif; University of Paris-Sud, Orsay, France.

X Fernandez

Data Direction, Institut Curie, Paris, France.

T Filleron

Biostatistics Unit, Institut Claudius Regaud, Institut Universitaire du Cancer de Toulouse-Oncopole, Toulouse, France.

M Kamal

Department of Drug Development and Innovation (D3i), Institut Curie, Paris, France. Electronic address: maud.kamal@curie.fr.

C Le Tourneau

Department of Drug Development and Innovation (D3i), Institut Curie, Paris, France; Inserm U900 Research Unit, Saint Cloud, France; Paris-Saclay University, Paris, France. Electronic address: Christophe.letourneau@curie.fr.

References

PubMed