Identification of Pathways to Mitigate Immune-Related Adverse Events With Cancer Immunotherapy

Study Overview
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Brief Summary
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This protocol is a prospective, observational study of participants receiving immunotherapy (checkpoint inhibitors, CPI) for cancer therapy, testing the hypothesis that patients with immune related cutaneous adverse events (ircAEs) have unique immunologic endotypes associated with polarized immune responses.

Official Title
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Identification of Pathways to Mitigate Immune-Related Adverse Events With Cancer Immunotherapy

Conditions
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Cancer

Intervention / Treatment
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* Drug: systemic corticosteroid or biologic


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Provision of signed and dated informed consent form Stated willingness to comply with all study procedures and availability for the duration of the study Male or female, >18 yo Diagnosis of solid tumor including, but not limited to, genitourinary/gynecologic, lung, gastrointestinal and melanoma Receiving, or prior to starting on, a checkpoint inhibitor Grade ≥ 2 ircAE (CTCAE v 5.0) (for cohort 1 only) An indication for system corticosteroids or biologic therapies as determined by the treating physician (for cohort 1 only) Life expectancy ≥ 12 weeks Exclusion Criteria: Daily use of systemic steroid treatment in the past 4 weeks (prednisone >10mg a day or equivalent) except for indications other than the cutaneous adverse event, and/or as an anti-emetic pre- or post-chemotherapy infusions. Enrollment in any investigational drug trial with a drug that has not been approved Taking other checkpoint inhibitors beyond anti-PD-(L)-1 or anti-CTLA-4 not yet indicated/approved for use Pregnancy Known blood borne infectious disease Current or pervious diagnosis of a leukemia or lymphoma Unable to give consent for study participation Life expectancy < 12 weeks Any other condition or diagnosis in the opinion of the investigator that would interfere with the study results

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| CPI with ircAE<br>Participants on check point inhibitors with immune related cutaneous adverse event | Drug: systemic corticosteroid or biologic<br>* Treatment with systemic corticosteroids or biologic therapies (for corticosteroid refractory patients or these in which corticosteroids are not the treatment of choice)<br>|
| no ircAE<br>Participants who do not have a cutaneous adverse event | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Immune Biomarkers | cytokines and chemokines | 30 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Presence of skin and circulating lipid biomarkers which occur during and after ircAEs | Proportion of long-chain and short-chain ceramides Amounts and relative proportion of lysophosphatidylcholine molecular species. sphingosine-1-phosphate, platelet activating factor, leukotriene E4, prostaglandin F2α, endocannabinoids anandamide and 2- arachidonoylglycerol. Peripheral blood mononuclear cell RNA for expression of GRalpha, GRbeta, Vitamin D 24- Hydroxylase FK506 binding protein 5, mitogen induced kinase phosphatase 1, interleukin, tumor necrosis factor alphal | 30 days | 
| Mechanisms associated with corticosteroid unresponsiveness in patients with ircAE | Proportion of long-chain and short-chain ceramides Amounts and relative proportion of lysophosphatidylcholine molecular species. sphingosine-1-phosphate, platelet activating factor, leukotriene E4, prostaglandin F2α, endocannabinoids anandamide and 2- arachidonoylglycerol. Peripheral blood mononuclear cell RNA for expression of GRalpha, GRbeta, Vitamin D 24- Hydroxylase FK506 binding protein 5, mitogen induced kinase phosphatase 1, interleukin, tumor necrosis factor alphal | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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cutaneous adverse events, checkpoint inhibitor, immuno-oncology