The purpose of this study is to test the safety and effectiveness of using brodalumab in patients who develop side effects from cancer immune therapy. Immune-related side effects are due to activation of the immune system in patients who previously received immunotherapy and the goal of this study is to help better control these side effects. Brodalumab is often used to treat patients with autoimmune diseases (diseases where the immune system is activated against normal organs) and safe doses and treatment schedules have been determined in these patients. Immune-related side effects appear to closely mirror these autoimmune conditions. Brodalumab has not been approved by the United States Food and Drug Administration (FDA) for use in immunotherapy side effects but it has been approved for treatment of autoimmune conditions.
The proposed study will evaluate the safety and efficacy of brodalumab in improving and resolving Immune-Related Adverse Events (irAEs) in patients treated with brodalumab. Eligible subjects must have an immune-related adverse event with the intent to treat it with steroids. Subjects will receive subcutaneous brodalumab for 24 weeks. Peripheral blood will be collected at all in-person study visits for mechanistic studies. Participants will be evaluated at week 0, 1, 2, 4, and then every 4 weeks after that until week 24 as dictated by the standard of care using a combination of telemedicine and face-to-face evaluations. Additional safety follow-up visits will occur at weeks 28 and 36. All patients will have the Columbia Suicide Severity Rating Scale (C-SSRS), and Patient Health Questionnaire-9 (PHQ-9) administered at all visits. The treatment protocol consists of subcutaneous brodalumab 210 mg administered at baseline and then at weeks 0, 1, and 2, then bi-weekly for a total of 24 weeks (the current FDA-approved dosing for plaque psoriasis). Glucocorticoids may be used at baseline at the discretion of the investigators, with the goal of tapering off of steroids over 4-8 weeks if tolerated (see proposed taper in appendix). Continued treatment beyond the 24-week course can be evaluated by the treating investigator and the Sponsor-Investigator, weighing risks versus clinical benefit.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
11
Brodalumab 210 mg subcutaneous injection
CT scans within 4 weeks of starting brodalumab and every 3 months during the study for tumor assessment
Columbia University Irving Medical Center
New York, New York, United States
RECRUITINGNumber of Adverse Events
The number of adverse events of each grade that occur and the number of adverse events attributed to brodalumab, as per the Common Terminology Criteria for Adverse Events version 5 (CTCAE v5).
Time frame: Up to 36 weeks
Percentage of primary Immune-Related Adverse Event (irAE) severity decreased
The percentage of patients whose primary irAE severity decreased by \>1 grade per CTCAE criteria from study completion to treatment discontinuation.
Time frame: 24 weeks
Percentage net decrease in the average steroid dose required for irAE management
The percentage of patients with a net decrease in the average steroid dose required for irAE management (defined by the ratio of the average steroid dose in prednisone equivalents over the 7 days following enrollment compared to the average dose in the 7 days prior to study completion).
Time frame: Up to 36 weeks
Proportion of Patients Successfully Tapered Off Steroids
The proportion of patients who can be tapered completely off of steroids (and remain off for a minimum of 1 week).
Time frame: Up to 36 weeks
Mean Time to Complete Resolution of irAE Symptoms
Mean time to complete resolution of irAE clinical manifestation ((as defined as absence of signs/symptoms consistent with the irAE or return to baseline symptoms prior to irAE development)).
Time frame: Up to 36 weeks
Change in Tumor Burden Assessed by RECIST Criteria at 24 Weeks
Change in tumor burden as measured by RECIST criteria comparing CT/MRI scan at the time of enrollment to CT/MRI scan at 24 weeks.
Time frame: 24 weeks
Proportion of Patients with Grade 3 or Higher Infection Events
The proportion of patients with \> grade 3 infection per CTCAE.
Time frame: Up to 36 weeks
Cumulative Steroid Exposure over 24 Weeks
Cumulative steroid exposure (in prednisone equivalents) over 24 weeks
Time frame: 24 weeks
FACT-G global assessment score
Change in the quality of life as measured by the Functional Assessment of Cancer Therapy - General (FACT-G) global assessment score. Score range is 0-108. Higher scores indicate a better quality of life, while lower scores suggest worse outcomes.
Time frame: Baseline and 24 weeks
Progression-free survival (PFS)
PFS is defined as the duration of time from the start of treatment to the time of progression or death, whichever occurs first, measured in months
Time frame: Up to 36 weeks
Overall Survival (OS)
OS is defined as the duration of time from either the date of diagnosis or the start of treatment that patients diagnosed with the disease are still alive, measured in months.
Time frame: Up to 36 weeks
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