Brodalumab for Cancer Immunotherapy Side Effects

Overseen By Research Nurse Navigator

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Brian Henick, MD

Must be taking: Systemic steroids

Must not be taking: Immunosuppressive agents

Disqualifiers: Severe depression, Drug abuse, Hepatitis, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 10

Duration: 24 weeks

11 Participants Needed

Trial Summary

Do I need to stop my current medications to join the trial?

The trial does not specify if you need to stop taking your current medications, but it does mention that additional immunosuppressive treatments (other than corticosteroids and brodalumab) are not allowed. It's best to discuss your current medications with the trial team.

Is Brodalumab safe for use in humans?

Brodalumab, also known as Siliq, Kyntheum, Lumicef, KHK4827, and AMG 827, has been studied for various conditions, primarily psoriasis. It is generally considered safe for human use, but it may cause side effects like infections, headache, and joint pain. Serious side effects, such as suicidal thoughts or behavior, have been reported, so monitoring by healthcare professionals is important. ^{1 2 3 4 5}

How does the drug Brodalumab differ from other treatments for cancer immunotherapy side effects?

Brodalumab is unique because it targets the interleukin-17 receptor, which is different from other treatments that often target immune checkpoint pathways like CTLA-4 or PD-1. This distinct mechanism may offer an alternative approach to managing immune-related side effects from cancer immunotherapy. ^{1 6 7 8 9}

What is the purpose of this trial?

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.

Research Team

Brian Henick, MD

Principal Investigator

Columbia University

Eligibility Criteria

This trial is for patients with various types of cancer who have experienced side effects from previous immunotherapy treatments. It's aimed at those needing to manage these immune-related adverse events, which are similar to autoimmune disease symptoms.

Inclusion Criteria

I tested negative for tuberculosis recently.

I have had a positive TB test but no symptoms, completed treatment, and no recent exposure or active TB.

I had a BCG vaccine but my QuantiFERON test for TB is negative.

Exclusion Criteria

PHQ-9 score greater >5 and < 20 without an established mental health provider who verifies stability in their depression

I am not allergic to brodalumab, corticosteroids, or any of their ingredients.

My doctor thinks I need more immune system treatment besides steroids.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive subcutaneous brodalumab for 24 weeks with evaluations at weeks 0, 1, 2, 4, and then every 4 weeks

24 weeks

8 visits (in-person and virtual)

Follow-up

Additional safety follow-up visits to monitor for adverse events and progression-free survival

12 weeks

2 visits (in-person)

Extension

Continued treatment beyond the 24-week course can be evaluated by the treating investigator and the Sponsor-Investigator

Treatment Details

Interventions

• Brodalumab

Trial Overview The study tests the safety and effectiveness of brodalumab, a drug approved for autoimmune diseases, in controlling side effects caused by cancer immunotherapies. Participants will undergo regular CT scans to monitor progress.

Participant Groups

Group I: brodalumab to treat irAEs in patient with solid tumors Experimental Treatment 2 Interventions

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

Brodalumab is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Siliq for:

• Moderate to severe plaque psoriasis

Approved in European Union as Kyntheum for:

• Moderate to severe plaque psoriasis

Approved in Canada as Siliq for:

• Moderate to severe plaque psoriasis

Who Is Running the Clinical Trial?

Brian Henick, MD

Lead Sponsor

Trials

2

Recruited

10+

Bausch Health

Collaborator

Trials

2

Recruited

40+

Findings from Research

CTLA-4 antagonists, a new class of immunomodulating antibodies, have shown effectiveness against cutaneous melanoma and other tumors, but they can cause immune-related adverse events (irAEs) such as colitis, dermatitis, and hepatitis.

While these side effects are generally mild and manageable with treatment, effective communication between patients and physicians, along with early intervention, is crucial to prevent serious complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The emerging toxicity profiles of anti-CTLA-4 antibodies across clinical indications. Di Giacomo, AM., Biagioli, M., Maio, M.[2020]

In a study of 249 melanoma patients, immune-related adverse events (irAEs) were observed in 74.6% of patients, with a notable correlation between the occurrence of irAEs and improved treatment outcomes in the non-adjuvant setting.

The frequency of irAEs was high in both treatment settings, but in the adjuvant setting, they did not correlate with disease relapse, suggesting that while irAEs may indicate better efficacy in some cases, they do not universally predict treatment success.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Frequency, Treatment and Outcome of Immune-Related Toxicities in Patients with Immune-Checkpoint Inhibitors for Advanced Melanoma: Results from an Institutional Database Analysis. Dimitriou, F., Staeger, R., Ak, M., et al.[2021]

A study analyzing 1568 reported cases of ocular adverse effects (OAEs) from BRAF and MEK inhibitors found that BRAF monotherapy is significantly linked to various eye issues, including iris and ciliary body abnormalities and anterior uveitis, indicating a need for careful monitoring of these side effects.

MEK inhibitor monotherapy was associated with retinal and choroid abnormalities, and the combination therapy of BRAF and MEK inhibitors showed potential for increased ocular toxicity, suggesting that personalized management strategies are necessary for patients undergoing combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ocular Safety Profile of BRAF and MEK Inhibitors: Data from the World Health Organization Pharmacovigilance Database. Mettler, C., Monnet, D., Kramkimel, N., et al.[2021]

The study confirms that PD-1 inhibitors like Pembrolizumab and Nivolumab improve response and survival rates in advanced melanoma patients, especially when combined with the CTLA-4 inhibitor Ipilimumab, which shows superior efficacy compared to monotherapies.

However, these immunotherapies are associated with significant immune-related adverse events, some of which can be life-threatening, highlighting the need for further studies to better understand their safety profiles and mechanisms of action.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Public Adverse Event Data Insights into the Safety of Pembrolizumab in Melanoma Patients. Schaefer, A., Sachpekidis, C., Diella, F., et al.[2020]

In a study of 91 patients undergoing treatment with immune checkpoint inhibitors for solid tumors, 74% showed signs of adjuvant-induced autoimmune/pro-inflammatory syndrome (ASIA), but the ASIA questionnaire did not effectively predict the risk of immune-related adverse events (irAES).

Combining the ASIA index with PD-L1 expression levels allowed for a predictive model of treatment efficacy, achieving 100% sensitivity and 70% specificity for predicting disease control rate, indicating a potential method for assessing treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The predictive potential of autoimmune-inflammatory syndrome induced by adjuvants (ASIA) criteria to assess the risk of adverse events and efficacy of immune checkpoint inhibitor therapy. Zhukova, N., Orlova, R., Malkova, A., et al.[2022]

In a study of 140 patients with advanced colorectal cancer, severe early skin reactions (grade ≥2) from cetuximab treatment were linked to improved overall survival, indicating that these reactions may serve as a positive prognostic indicator.

While skin toxicity did not negatively affect overall quality of life, severe mucositis/stomatitis significantly reduced quality of life, highlighting the need for effective management of this adverse event to maintain treatment compliance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A prospective Phase II study to examine the relationship between quality of life and adverse events of first-line chemotherapy plus cetuximab in patients with KRAS wild-type unresectable metastatic colorectal cancer: QUACK trial. Iwamoto, S., Ooki, A., Morita, S., et al.[2021]

In a review of clinical trials for colorectal cancer, 76.9% of studies on cetuximab reported dermatologic adverse drug reactions (dADRs), with 50% showing a positive correlation between these reactions and patient survival, indicating that dADRs may be relevant for treatment outcomes.

In contrast, only 42.9% of studies on panitumumab reported dADRs, highlighting significant variability in reporting practices, which limits the ability to assess patient risk and compare the safety profiles of these treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Completeness in the reporting of dermatologic adverse drug reactions associated with monoclonal antibody epidermal growth factor receptor inhibitors in phase II and III colorectal cancer clinical trials. Bauer, KA., Hammerman, S., Rapoport, B., et al.[2018]

Ipilimumab is an immunotherapy that works by inhibiting CTLA-4, leading to enhanced immune system activation, which can effectively treat advanced melanoma and other cancers.

Common side effects of ipilimumab are mostly mild to moderate (grade I or II) and include immune-mediated reactions like inflammatory diarrhea and pruritus, but serious side effects can be managed effectively with corticosteroids or other treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ipilimumab for advanced melanoma: a nursing perspective. Ledezma, B.[2017]

Nivolumab and ipilimumab, two FDA-approved immunotherapeutic agents targeting PD-1 and CTLA-4, are effective in treating various cancers but can cause significant immune-related adverse effects (irAEs).

In a case study of a 66-year-old female patient, steroid-resistant colitis induced by these checkpoint inhibitors was successfully treated with infliximab, highlighting a potential management strategy for severe irAEs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of Immune Checkpoint Inhibitor Induced Colitis with Infliximab. Tidwell, C., Gutnik, S.[2020]

References

1. United States pubmed.ncbi.nlm.nih.gov

The emerging toxicity profiles of anti-CTLA-4 antibodies across clinical indications. [2020]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Frequency, Treatment and Outcome of Immune-Related Toxicities in Patients with Immune-Checkpoint Inhibitors for Advanced Melanoma: Results from an Institutional Database Analysis. [2021]

3. United States pubmed.ncbi.nlm.nih.gov

Ocular Safety Profile of BRAF and MEK Inhibitors: Data from the World Health Organization Pharmacovigilance Database. [2021]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Public Adverse Event Data Insights into the Safety of Pembrolizumab in Melanoma Patients. [2020]

5. United States pubmed.ncbi.nlm.nih.gov

The predictive potential of autoimmune-inflammatory syndrome induced by adjuvants (ASIA) criteria to assess the risk of adverse events and efficacy of immune checkpoint inhibitor therapy. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

A prospective Phase II study to examine the relationship between quality of life and adverse events of first-line chemotherapy plus cetuximab in patients with KRAS wild-type unresectable metastatic colorectal cancer: QUACK trial. [2021]

7. United States pubmed.ncbi.nlm.nih.gov

Completeness in the reporting of dermatologic adverse drug reactions associated with monoclonal antibody epidermal growth factor receptor inhibitors in phase II and III colorectal cancer clinical trials. [2018]

8. United States pubmed.ncbi.nlm.nih.gov

Ipilimumab for advanced melanoma: a nursing perspective. [2017]

9. United States pubmed.ncbi.nlm.nih.gov

Treatment of Immune Checkpoint Inhibitor Induced Colitis with Infliximab. [2020]