Clinical trial NCT05139706: Montreal Immune-Related Adverse Events (MIRAE) Study
Official title: Montreal Database and Biorepository of Cancer Patients Treated With Immune Checkpoint Inhibitors for the Study of Immune-related Adverse Events
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Cancer
Immune System Disorder
Inflammatory Reaction
Autoimmune Diseases
Keywords: irAEs
ICI (ICB)
CTLA-4
PD-1
PDL-1
Pembrolizumab
Nivolumab
Ipilimumab
Cemiplimab
Atezolizumab
Avelumab
Durvalumab
Lead sponsor: Sir Mortimer B. Davis - Jewish General Hospital
Sponsor class: OTHER
First posted: 2021-12-01
Enrollment: 1000
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Cancer patients treated with ICI, patients with primary autoimmune or autoinflammatory diseases and healthy volunteers.

Brief summary: Immune checkpoint inhibitors (ICI) are among the most promising approaches to fighting cancer. However, a substantial percentage of patients experience off-target adverse effects in the form of mild to severe inflammation in different organs, commonly called immune-related adverse events (irAEs). irAEs can lead to treatment discontinuation, or can be life-threatening in extreme cases. The causes of irAEs are largely unknown and there are no reliable predictive biomarkers. The Montreal Immune-Related Adverse Events (MIRAE) study collects clinical information and biospecimens (blood, tissue, stool) from cancer patients treated with ICI to facilitate research on the identification of predictive biomarkers of irAEs, their causes, and the design of effective management strategies.

Detailed description: Background:

During cancer development and progression, cancer cells evolve to evade natural anti-tumor immunity. One major pathway of immune evasion involves the engagement of co-inhibitory receptors present on the surface of T cells that modulate their activation status, and therefore their ability to directly or indirectly kill tumor cells. These receptors are known as immune checkpoint inhibitors (ICI). Blockade of ICI using antibodies leads to prolonged T cell activation and unleashes the anti-tumor activity of T cells. ICI treatment for cancer has led to unprecedented advances in cancer treatment by prolonging survival of patients with previously refractory cancers. Among these ICI, CTLA-4, PD-1 and PDL-1 inhibitors have been shown to be effective cancer immunotherapies, and many other ICIs are now in pre-clinical and clinical development.

Although ICI cancer therapy is overall well tolerated, off-target immune reactions targeting healthy cells or tissues called immune-related adverse events (irAEs) develop in a substantial percentage of patients limiting the use of ICI therapy. irAEs target range from mild to severe and fatal. Currently, there are no reliable predictive biomarkers for the wide spectrum of irAEs and their clinical management in severe cases involves discontinuation of ICI therapy.

The Montreal Immune-Related Adverse Events (MIRAE) study is a biobank that collects human biological specimens (e.g., tissue, blood, plasma, PBMCs, saliva, stool) and the associated clinical information from cancer patients treated with ICI with the purpose of promoting research to identify clinical and biological predictors and mechanisms of irAEs, evaluate the effects of immunomodulatory treatment of irAEs on tumor biology, and investigate treatment strategies to minimize irAEs.

Objectives:

1. Identify biomarkers predictive of irAEs, including cellular, immunologic, genetic and microbial biomarkers; and
2. Evaluate the effects of immunomodulatory treatment of irAEs, and investigate treatment strategies that minimize irAEs and maximize ICI efficacy.

Eligibility criteria: Inclusion Criteria:

* \>= 18 years of age
* cancer patients treated with ICI therapy (e.g., anti-CTLA-4, anti-PD-1, anti-PD-L1, and combinations)
* patients with primary autoimmune or autoinflammatory diseases that resemble immune-related adverse events (irAEs)
* healthy volunteers with non-inflammatory disorders, and without any history of cancer

Exclusion Criteria:

* Participants not able to provide informed consent

Primary outcomes:
measure: Incidence of immune-related adverse events
timeFrame: Up to 5 years
measure: Biomarkers of irAE
timeFrame: Up to 5 years
Secondary outcomes:
Other outcomes:
Locations:
city: Montreal
country: Canada
facility: Jewish General Hospital
state: Quebec
Study officials:
affiliation: Jewish General Hospital, McGill University
name: Marie Hudson, MD
role: PRINCIPAL_INVESTIGATOR
References: