Biomarkers of Immune-Related Toxicity

Study Overview
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Brief Summary
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This is a single-center, correlative pilot study evaluating potential biomarkers predictive of immune-related adverse events associated with immune checkpoint inhibitor therapy.

Detailed Description
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This is a single-center, correlative pilot study evaluating potential biomarkers predictive of immune-related adverse events associated with immune checkpoint inhibitor therapy. The study includes a control population of patients receiving standard chemotherapy as a comparator. Patients will undergo blood draws at 4 time-points while on standard of care treatment. There are no study-related medications or interventions beyond blood sampling.

Official Title
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Identifying Biomarkers of Immune-Related Toxicity in Cancer Patients Treated With Immune Checkpoint Inhibitors; A Pilot Project

Conditions
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Cancer, Metastatic Cancer

Intervention / Treatment
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* Other: Blood Testing


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Metastatic solid tumor cancer of any primary site, with the exception of lymphoma ≥18 years of age Life expectancy >6 months Starting new regimen of ipilimumab, nivolumab, pembrolizumab or atezolizumab as a single agent or in combination according to standard of care or through compassionate use granted by the pharmaceutical company (immune checkpoint inhibitor arm only) OR Starting new regimen of standard cytotoxic chemotherapy (control arm only) Provision to sign and date the consent form Stated willingness to comply with all study procedures and be available for the duration of the study Exclusion Criteria: Prior immune checkpoint inhibitor therapy with anti-CTLA4, anti-PD1 or anti-PD-L1 targeting agent Known autoimmune disease Known acute or chronic infection, including viral infections such as Hepatitis B, C, and HIV Chronic treatment with immune suppressive medications, including steroids, at the time of study enrollment Concomitant treatment with a monoclonal antibody in addition to cytotoxic chemotherapy (i.e. bevacizumab, cetuximab, trastuzumab) (control arm only) Known pregnancy or lactation

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 100 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 |
| --- | --- |
| Immune Checkpoint Inhibitor Therapy<br>Patients starting treatment with ipilimumab, nivolumab, pembrolizumab, or atezolizumab, alone or in combination, for treatment of a metastatic solid tumor cancer will be enrolled. Patients will receive checkpoint inhibitor therapy per standard protocol. There are no study-related medications or interventions beyond blood testing. | Other: Blood Testing<br>* Patients will undergo therapy per standard protocol. There are no study-related medications or interventions beyond blood testing.<br>|
| Control<br>An additional 18 patients starting standard chemotherapy will be enrolled as a control population. Patients will receive chemotherapy per standard protocol | Other: Blood Testing<br>* Patients will undergo therapy per standard protocol. There are no study-related medications or interventions beyond blood testing.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Identifying biomarkers predictive of immune-related toxicity associated with immune checkpoint inhibitor therapy. | Difference in baseline inflammatory/autoimmune marker(s) in patients developing immune-related adverse events on immune checkpoint inhibitor therapy according to CTCAE v 4.0 versus those who do not | 30 Months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in inflammatory/autoimmune markers. | To evaluate the change in inflammatory/autoimmune markers prior to and at 3 time points on immune checkpoint inhibitor therapy, with comparison to patients treated with standard chemotherapy | 6 Months | 
| Change in inflammatory/autoimmune markers | To evaluate the impact of change in these markers on patient reported adverse events using the PRO-CTCAE | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Immune Checkpoint Inhibitors, Biomarkers, Immune Related Adverse Event