Predictive Markers of Immune-related Adverse Events in Patients Treated With Immune Stimulatory Drugs (PREMIS)

Gustave Roussy

Status: Enrolling

Conditions: Cancer

Treatments: Procedure: Blood sample

Study type: Interventional

Funder types: Other

Identifiers

NCT03984318

2018/2728 (Other Identifier)

2018-A01257-48

Details and patient eligibility

About

The prospect of effective immunotherapies for the treatment of patients with cancer is now a clinical reality thanks to the approval of monoclonal antibodies (mAbs) specifically blocking immune checkpoints or ligands such as CTLA-4, PD-1 and PD-L1. However, these drugs can also induce inflammatory and/or auto-immune complications (Immune-related Adverse Events; IrAE). IrAE can affect all tissues and sometimes irreversibly. IrAE may be severe or fatal in the absence of timely and adequate care with anti-inflammatory drugs (steroids) or more specific immunosuppressants. Thus, IrAE are a new type of toxicities in oncology and represent one of the major limitations for the development of immunotherapy combination therapies. These IrAE are yet unpredictable. Indeed, the induction of immunity relies on the host's immune status and it differs from one patient to another and so far nobody has identified the underlying mechanisms responsible for irAE outbreaks.

Enrollment: 1,240 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Age ≥ 18
• Patients with either liquid (hematological) or solid malignancy, in any line of treatment.
• Patients treated with an immunotherapy based on immune checkpoint targeted monoclonal antibody (mainly anti-PD-1, anti-PD-L1, anti-CTLA-4 monotherapies and combinations)
• Patient should understand, sign, and date the written informed consent form prior to any protocol-specific procedures performed. Patient should be able and willing to comply with study visits and procedures as per protocol.
• Patients must be affiliated to a social security system or beneficiary of the same
• Patient able to read and write French
• Women of child bearing potential must have a negative serum or urine β-HCG pregnancy test within 14 days prior to initiation of treatment
• Sexually active women of childbearing potential must agree to use a highly effective method of birth control supplemented by a barrier method during the trial and for the duration planned in the SmPC or the study protocol after the last administration of each immunotherapy
• Sexually active males patients must agree to use condom during the study and for the duration planned in the SmPC or the study protocol after the last administration of each immunotherapy. Also, it is recommended their women of childbearing potential partner use a highly effective method of contraception

Exclusion criteria

• Patients treated with immunotherapies that do not contain at least one immunomodulatory drug targeted against a co inhibitory checkpoint molecule
• Known severe hypersensitivity reactions to monoclonal antibodies
• Pregnant or breastfeeding women
• Patient under guardianship or deprived of his liberty by a judicial or administrative decision or incapable of giving its consent

Trial design

Primary purpose: Diagnostic

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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1,240 participants in 1 patient group

patient treated with immune checkpoint targeted monoclonal AB

Experimental group

Description:

Blood (plasma+serum+PBMC) collection before the start of immunotherapy, at week 6 and upon grade ≥2 irAE.

Treatment:

Procedure: Blood sample