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Poster Display session

219 - CHECK'UP: A prospective cohort study to identify predictive factors of response and mechanisms of resistance to PD-1 and PD-L1 antagonists

Date

14 Dec 2018

Session

Poster Display session

Presenters

Fréderique Penault-Llorca

Citation

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

Authors

F. Penault-Llorca1, C. Caux2, S. Depil3, C. Le Tourneau4, M. Pérol5, C. Robert6, V. Soumelis7, D. Couch8, N. Isambert9, Y. Fernandez10, T. Filleron11, G. Vassal6

Author affiliations

  • 1 Direction Générale, Centre Jean Perrin, 63011 - Clermont-Ferrand/FR
  • 2 Inserm, Centre Léon Bérard, 69008 - Lyon/FR
  • 3 Cancer Immunotherapy Program, Centre Léon Bérard, 69008 - Lyon/FR
  • 4 Département D'oncologie Médical, Institut Curie, 75005 - Paris/FR
  • 5 Département D'oncologie Médical, Centre Léon Bérard, 69008 - Lyon/FR
  • 6 Département D'oncologie Médical, Gustave Roussy, 94805 - Villejuif/FR
  • 7 Clinical Immunology Laboratory, Institut Curie, 75005 - Paris/FR
  • 8 R&d, UNICANCER, 75654 - Paris/FR
  • 9 Département D'oncologie Médical, Centre Georges-François Leclerc, 21000 - Dijon/FR
  • 10 Département D'oncologie Médical, Institut de Cancérologie de Lorraine, 54519 - Vandoeuvre-lès-Nancy/FR
  • 11 Clinical Trials Office, Institut Claudius Rigaud, Toulouse/FR
More

Resources

Abstract 219

Background

Immune checkpoint blockade represents a major breakthrough in cancer therapy with recent approvals of PD-1 or PD-L1 antagonists in a range of indications. Phase 3 studies have demonstrated response rates varying from 13% (head and neck squamous cell carcinoma [HNSCC]) to 40% (melanoma) in sensitive diseases, and impressively durable responses in individual patients. The overall rate of response remains relatively low however. Even in immune-sensitive diseases such as melanoma the majority of tumours do not respond to immunotherapy alone and most tumours will eventually develop resistance to the treatment. Furthermore, although PD-1/PD-L1 antagonists are generally well tolerated, a small but significant number of patients experience severe immune-related toxicity, the risk factors of which are poorly understood. Identifying which patients will most benefit from PD-1/PD-L1 antagonist therapy and the mechanisms of resistance are of critical importance for clinicians. The CHECK’UP trial aims to address this question by studying approved PD-1/PD-L1 antagonist treatment across three cancer indications: melanoma, non-small cell lung cancer (NSCLC) and HNSCC.

Trial design

This prospective, multicentre cohort trial will study 670 patients in 3 parallel groups set to receive one of the single agent PD-1 or PD-L1 antagonists authorised for use in France as standard care for melanoma, NSCLC or HNSCC. Clinical and biological sample data (tumour, blood, microbiome) collected at study entry and throughout the treatment period will be analysed to identify potential response biomarkers. Patients will be followed for 5 years. A penalized logistic regression model will be used to identify associations between different parameters and response to treatment in a training cohort, made up of the first patients included, and to develop a predictive response signature for each indication. The performance of this signature will then be tested in an independent validation cohort comprised of the remaining patients. Mechanisms of primary and acquired resistance, occurrence of long-term treatment related toxicity and a cost/benefit assessment of treatment in a real-life setting will also be explored.

Editorial acknowledgement

Clinical trial identification

Legal entity responsible for the study

UNICANCER.

Funding

Fondation ARC pour la recherche sur le cancer.

Disclosure

All authors have declared no conflicts of interest.

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