Using brodalumab to treat immune-related side effects from cancer therapy

Safety and Efficacy of Brodalumab in the Treatment of Immune-Related Adverse Events: A Pilot Study

This study is testing if brodalumab can help cancer patients who are having immune-related side effects from their immunotherapy treatment feel better.

Quick facts

• Phase: PHASE1
• Study type: Interventional
• Enrollment: 11 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Columbia University (other)
• Drugs / interventions: brodalumab, infliximab, vedolizumab, tocilizumab, immunotherapy
• Locations: 1 site (New York, New York)
• Trial ID: NCT06673329 on ClinicalTrials.gov

What this trial studies

This study aims to evaluate the safety and effectiveness of brodalumab in patients experiencing immune-related adverse events (irAEs) following cancer immunotherapy. Participants will receive subcutaneous brodalumab for 24 weeks, with assessments conducted at regular intervals to monitor their response and any side effects. The study will also involve collecting peripheral blood for mechanistic studies and utilizing telemedicine alongside in-person evaluations. The goal is to improve the management of irAEs, which can significantly impact the quality of life for cancer patients undergoing immunotherapy.

Who should consider this trial

Good fit: Ideal candidates include adults over 18 with a diagnosis of an immune-related adverse event suspected to be IL-17 mediated, who have previously received immunotherapy for advanced or metastatic solid organ malignancies.

Not a fit: Patients who are being treated with curative intent or those without a clinically suspected IL-17 mediated immune-related adverse event may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new option for managing immune-related side effects in cancer patients, potentially improving their overall treatment experience and outcomes.

How similar studies have performed: While brodalumab has been used successfully for autoimmune conditions, its application for treating immune-related adverse events in cancer therapy is novel and has not been extensively tested in prior studies.

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

Where this trial is running

New York, New York

• Columbia University Irving Medical Center — New York, New York, United States (RECRUITING)

Study contacts

• Principal investigator: Brian Henick, MD — Columbia University
• Study coordinator: Research Nurse Navigator

Conditions: Breast Cancer, Esophageal Cancer, Kidney Cancer, Lung Cancer, Thyroid Cancer, Gynecologic Cancer, Pancreatic Cancer, Stomach Cancer