Brodalumab In The Treatment Of Immune-Related Adverse Events

Study Overview

Brodalumab in the Treatment of Immune-Related Adverse Events

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.

Breast Cancer
Esophageal Cancer
Kidney Cancer
Lung Cancer
Thyroid Cancer
Gynecologic Cancer
Pancreatic Cancer
Stomach Cancer
Brain Tumor
Colon Cancer
Rectal Cancer
Head and Neck Cancer
Oral Cancer
Liver Cancer
Skin Cancer
Prostate Cancer
Testicular Cancer
Solid Tumor

DRUG: Brodalumab
RADIATION: CT scan

AAAV1382

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2024-10-31	Results First Submitted N/A	Last Update Submitted that met QC Criteria 2025-05-09
First Submitted that Met QC Criteria 2024-11-01	Results First Submitted that Met QC Criteria N/A	Last Update Posted (ACTUAL) 2025-05-14
First Posted (ACTUAL) 2024-11-04	Results First Posted N/A	Last Verified 2025-05

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Na

Interventional Model:
Single Group

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment
EXPERIMENTAL: brodalumab to treat irAEs in patient with solid tumors Brodalumab 210 mg subcutaneous injection on weeks 0, 1, 2 followed by administration every 2 weeks until week 24	DRUG: Brodalumab Brodalumab 210 mg subcutaneous injection RADIATION: CT scan CT scans within 4 weeks of starting brodalumab and every 3 months during the study for tumor assessment

Participant Group/Arm

Intervention/Treatment

EXPERIMENTAL: brodalumab to treat irAEs in patient with solid tumors

Brodalumab 210 mg subcutaneous injection on weeks 0, 1, 2 followed by administration every 2 weeks until week 24

DRUG: Brodalumab

Brodalumab 210 mg subcutaneous injection

RADIATION: CT scan

CT scans within 4 weeks of starting brodalumab and every 3 months during the study for tumor assessment

Primary Outcome Measures	Measure Description	Time Frame
Number 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).	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.	24 weeks

Secondary Outcome Measures	Measure Description	Time Frame
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).	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).	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)).	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.	24 weeks
Proportion of Patients with Grade 3 or Higher Infection Events	The proportion of patients with > grade 3 infection per CTCAE.	Up to 36 weeks
Cumulative Steroid Exposure over 24 Weeks	Cumulative steroid exposure (in prednisone equivalents) over 24 weeks	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.	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	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.	Up to 36 weeks

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Name: Research Nurse Navigator

Phone Number: 212-342-5162

Email: cancerclinicaltrials@cumc.columbia.edu

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

Ability to provide written informed consent by subject or guardian
Individuals >18 years of age
Diagnosis of an irAE clinically suspected to be IL-17 mediated
Intent-to-treat or prior treatment with systemic steroids for irAE management
Histology-proven primary advanced or metastatic solid organ malignancy treated with immunotherapy. Patients being treated with curative intent are not eligible to enroll.
Subject has a negative test for tuberculosis during screening defined as either: negative purified protein derivative (PPD) (< 5 mm of induration at 48 to 72 hours after test is placed) OR negative QuantiFERON test. Tuberculosis testing must be performed within 30 days prior to trial initiation.
Subjects with a positive PPD and a history of Bacillus Calmette-Guérin vaccination are allowed with a negative QuantiFERON test.
Subjects with a positive PPD test (without a history of Bacillus Calmette-Guérin vaccination) or subjects with a positive or indeterminate QuantiFERON test are allowed if they have all of the following: no symptoms of tuberculosis (defined as fever, shortness of breath, cough or night sweats), documented history of a completed course of adequate prophylaxis (per local standard of care), no known exposure to a case of active tuberculosis after most recent prophylaxis, no evidence of active tuberculosis on chest radiograph within 3 months prior to the first dose of brodalumab.

Estimated creatinine clearance < 40 mg/min
Active suicidal ideation or severe depression (as defined by the Diagnostic and Statistical Manual of Mental Disorders Version IV criteria (DSM-IV)) at the time of enrollment or a PHQ-9 score > 20
History of prior suicide attempts
PHQ-9 score greater >5 and < 20 without an established mental health provider who verifies stability in their depression
Current or prior drug or alcohol abuse within the past 6 months (as defined by the DSM IV)
In the opinion of the investigator, the patient requires additional immunosuppressive treatment (other than corticosteroids and brodalumab)
Known hypersensitivity or contraindication to brodalumab, corticosteroids or any components of brodalumab
Prior treatment with brodalumab
Pregnancy, breastfeeding, or use of a nonreliable method of contraception

For patients assigned female at birth: lack of willingness to use highly effective methods of birth control during treatment and for at least 4 weeks after the last dose of brodalumab (except if surgically sterile or at least 2 years postmenopausal, with postmenopausal status confirmed by Follicle-Stimulating Hormone (FSH) in the postmenopausal range).
Highly effective methods of birth control include: use of hormonal contraceptives that inhibit ovulation, hormone-releasing intrauterine devices, and copper intrauterine devices. Oral contraceptive pills must be supplemented by a barrier method.
Patients planning to become pregnant while enrolled in the study and within 4 weeks after the last dose of brodalumab will not be permitted to enroll
Chronic or current severe infection requiring IV therapy
Evidence of active hepatitis B, C, or tuberculosis.
History of latent tuberculosis infection which is incompletely treated based upon local standard of care or which was never treated
History of or active Crohn's disease.
Myocardial infarction, unstable angina pectoris or stroke within the past 12 months prior to the first investigational product dose
Any concurrent medical condition or electrocardiogram (ECG) abnormality that, in the opinion of the investigator, could cause this study to be detrimental to the subject.
Any medical condition or treatment for a condition that, in the opinion of the investigator, might interfere with participation in the study or affect the reliability of clinician assessment or patient self-report
Other known clinically significant active medical conditions, such as:

Severe cardiovascular disease, including advanced heart failure (American Heart Association Stage D)
Aspartate aminotransferase (AST) and or alanine aminotransferase (ALT) greater than 2 times the upper limit of normal or greater than 3 times the upper limit of normal in patients with liver metastases measured on at least two separate occasions
Direct bilirubin greater than or equal to 1.5 mg/dL in patients with or without liver metastases
Bone marrow insufficiency unrelated to the irAE (according to investigator judgment) with White Blood Cell (WBC) <2000/mm3, absolute neutrophil count <1500/ mm3, thrombocytopenia (platelet count) <50,000/mm3, hemoglobin < 8.0 g/dL
Plan to proceed with further curative intent treatment for cancer at the time of enrollment despite the presence of irAE
Participation in another therapeutic clinical trial and receipt of investigational drugs within 4 weeks before the screening visit
Previous diagnosis of an autoimmune disease or administration of immunosuppressants in a time frame that would impede interpretation of brodalumab administration
Planned use of immunosuppressive agents other than steroids (including infliximab, vedolizumab, tocilizumab etc.) or administration of such agents within 28 days of trial initiation
Administration of live-virus vaccines within 4 weeks before the first dose of brodalumab

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Bausch Health

Investigators

PRINCIPAL_INVESTIGATOR: Brian Henick, MD, Columbia University

Publications

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

No publications available

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Clinical Trial Record