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

Congress : ESMO

Authors : Fréderique Penault-Llorca, Christophe Caux, Stéphan Depil, Christophe Le Tourneau, Maurice Pérol, Caroline Robert, Vassili Soumelis, Daniel Couch, Nicolas Isambert, Yolanda Fernandez, Thomas Filleron, Gilles Vassal.

Experts group or program : Groupe immuno-oncologie (GIO)

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.

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