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

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.

Study Overview

• Status: Recruiting
• Conditions: Cancer
• Intervention / Treatment: Procedure: Blood sample

• Study Type: Interventional
• Enrollment (Anticipated): 1240
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Aurélien Marabelle, MD; Phone Number: +33 (0)1 42 11 42 96; Email: aurelien.marabelle@gustaveroussy.fr
• Study Contact Backup: Name: Nathalie Chaput, MD; Phone Number: +33 (0)1 42 11 56 55; Email: nathalie.chaput@gustaveroussy.fr

Study Locations

• France
  • Chevilly-Larue, France, 94550
    • Recruiting
    • Gustave Roussy
    • Contact: Meriem MOKDAD-ADI
  • Le Kremlin-Bicêtre, France, 94270
    • Not yet recruiting
    • Hôpital Bicêtre
    • Contact: Olivier LAMBOTTE
  • Le Plessis-Robinson, France, 92350
    • Not yet recruiting
    • Hopital Marie Lannelongue
    • Contact: Jérôme LE PAVEC
  • Villejuif, France, 94800
    • Not yet recruiting
    • Hopital Paul Brousse
    • Contact: Eleonora DE MARTIN
  • Val De Marne
    • Villejuif, Val De Marne, France, 94805
      • Recruiting
      • Gustave Roussy
      • Contact: François-Xavier DANLOS, MD; Phone Number: +33 (0)1 42 11 42 96; Email: aurelien.marabelle@gustaveroussy.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: patient treated with immune checkpoint targeted monoclonal AB; Blood (plasma+serum+PBMC) collection before the start of immunotherapy, at week 6 and upon grade ≥2 irAE.	Procedure: Blood sample; Blood (plasma+serum+PBMC) collection before the start of immunotherapy, at week 6 and upon grade ≥2 irAE.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Incidence of Immune-related Adverse Events (irAE)	up to 5 years

Collaborators and Investigators

• Sponsor: Gustave Roussy, Cancer Campus, Grand Paris

Study record dates

Study Major Dates

• Study Start (Actual): December 12, 2018
• Primary Completion (Anticipated): December 11, 2026
• Study Completion (Anticipated): December 11, 2028

Study Registration Dates

• First Submitted: June 7, 2019
• First Submitted That Met QC Criteria: June 11, 2019
• First Posted (Actual): June 13, 2019

Study Record Updates

• Last Update Posted (Actual): May 27, 2022
• Last Update Submitted That Met QC Criteria: May 24, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Other Study ID Numbers: 2018-A01257-48; 2018/2728 (Other Identifier: CSET number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No