Brodalumab in the Treatment of Immune-Related Adverse Events

Launched by BRIAN HENICK, MD · Nov 1, 2024

Keywords

ClinConnect Summary

This clinical trial is studying a medication called brodalumab to see if it can help manage side effects caused by cancer treatments that boost the immune system. These side effects, known as immune-related adverse events (irAEs), can occur after patients receive immunotherapy for various types of cancer, including breast, lung, and kidney cancer. The goal is to find out if brodalumab can safely reduce these side effects and improve patients' quality of life. While brodalumab is approved for treating autoimmune diseases, it hasn't yet been approved for managing irAEs from cancer treatments.

To participate in the trial, patients must be over 18 years old and have a solid tumor cancer that has been treated with immunotherapy. They should also have experienced side effects that are suspected to be related to an immune response. Eligible participants will need to give their consent to join and will have regular check-ins for safety while receiving brodalumab. It’s important to note that this trial is currently recruiting participants, and patients should discuss with their healthcare provider to see if they might qualify.

Gender

ALL

Eligibility criteria

• Inclusion Criteria:
• • 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.
• Exclusion Criteria:
• • 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