Clinical trial NCT06993727: Autoimmune Endocrine Disease Related Antibodies Before the Start of Immune Checkpoint Inhibitor Therapy
Official title: Prospective Study of Autoimmune Endocrine Disease-related Antibodies Before the Start of Immune Checkpoint Inhibitor Therapy
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Autoimmunity
Lead sponsor: Brugmann University Hospital
Sponsor class: OTHER
First posted: 2025-05-29
Enrollment: 500
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

Brief summary: Promising treatments have been added to the oncologist's arsenal in recent years. Treatments that, unlike conventional chemotherapy, do not aim to destroy cancer cells directly, but rather activate the patient's own immune system to recognize and attack tumor cells again. This new treatment is called immune checkpoint therapy. This involves administering antibodies (large Y-shaped proteins that can stick to the surface of cells) that remove the brakes from the immune system.

The disadvantage of this innovative treatment is that the rejuvenated immune system can also attack cells that we want it not to recognize - our own body's cells. This is called autoimmunity. Patients who receive immune checkpoint therapy may suffer from symptoms such as skin rashes, diarrhea, hepatitis or hypothyroidism.

The purpose of this study is to find biomarkers predictive of the development of these side effects, and possibly also predict a better outcome of the cancer therapy. The investigators will also look for the presence of antibodies against the endocrine glands (glands that produce hormones, such as the thyroid, adrenal, pituitary, and pancreas) before the start of the immune therapy.

Detailed description: Immune checkpoint inhibitor therapy (ICI) is the current standard of care for many malignancies, due to its unique mechanism of action. These therapies release the brakes of the immune system by targeting cytotoxic T-lymphocyte antigen-4 (CTLA-4, e.g., ipilimumab, tremelimumab), programmed cell death-1 (PD-1, e.g., cemiplimab, dostarlimab, pembrolizumab, nivolumab) or its ligand (PD-L1, e.g., atezolizumab, avelumab, durvalumab). The flip side of the coin are immune-related adverse events (IrAE), including skin, intestinal and endocrinological toxicity, although any organ system can potentially be affected.

The prospective follow-up of the endocrine autoantibodies is an area of interest as the presence of thyroid autoantibodies is associated with the occurrence of thyroiditis with immunotherapy.

In turn, the occurrence of thyroiditis with immunotherapy is related to improved oncologic prognosis. Therefore, it would be of value to analyze whether the presence of thyroid autoimmunity (with positive thyroperoxidase and/or thyroglobulin autoantibodies) before the start of immunotherapy could be a marker of improved oncologic prognosis and outcome.

Furthermore, there is a gap in our knowledge of the impact of autoantibodies against less common endocrinopathies, such as hypophysitis (inflammation of the pituitary gland), adrenalitis (inflammation of the adrenal glands) or pancreas (type-1 like diabetes mellitus). Finding a prognostic factor for these types of endocrinopathy is equally important, as these patients may present with life-threatening endocrinopathy (adrenal crisis, diabetic ketoacidosis) and should be recognized and treated in a timely manner.

The main purpose of the current study is to evaluate the association between the autoimmune endocrine disease-related antibodies, the development of endocrine irAE and the impact on the tumor response including progression-free survival and overall survival.

For this study, the investigators aim to perform a blood sample before and during the immunotherapy, for the analysis of the autoimmune endocrine disease related antibodies (Ab): anti-thyroglobulin Ab (aTg), anti-thyroperoxidase Ab (aTPO), anti-TSH-receptor Ab (TSI), pituitary Ab, adrenal Ab, and anti-GAD. The included patients will be prospectively followed up.

Eligibility criteria: Inclusion Criteria:

* All subjects eligible for immune checkpoint therapy at the participating study sites. The cohort will consist of all subjects who consent to participate, and to use their information for future research and publication in a scientific journal.

Exclusion Criteria:

* Pregnancy

Primary outcomes:
measure: Blood level of anti-thyroglobulin antibodies (aTg)
timeFrame: Baseline (before the start of the immunotherapy)
measure: Blood level of anti-thyroglobulin antibodies (aTg)
timeFrame: 3 months after baseline
measure: Blood level of anti-thyroglobulin antibodies (aTg)
timeFrame: 6 months after baseline
measure: Blood level of anti-thyroperoxidase antibodies (aTPO)
timeFrame: Baseline (before the start of immunotherapy)
measure: Blood level of anti-thyroperoxidase antibodies (aTPO)
timeFrame: 3 months after baseline
measure: Blood level of anti-thyroperoxidase antibodies (aTPO)
timeFrame: 6 months after baseline
measure: Blood levels of TSH receptor antibodies (TRAb)
timeFrame: Baseline (before the start of immunotherapy)
measure: Blood levels of TSH receptor antibodies (TRAb)
timeFrame: 3 months after baseline
measure: Blood levels of TSH receptor antibodies (TRAb)
timeFrame: 6 months after baseline
measure: Blood level of pituitary antibody
timeFrame: Baseline (before the start of immunotherapy)
measure: Blood level of pituitary antibody
timeFrame: 3 months after baseline
measure: Blood level of pituitary antibody
timeFrame: 6 months after baseline
measure: Blood level of adrenal antibody
timeFrame: Baseline (before the start of immunotherapy)
measure: Blood level of adrenal antibody
timeFrame: 3 months after baseline
measure: Blood level of adrenal antibody
timeFrame: 6 months after baseline
measure: Blood level of anti-glutamic acid decarboxylase (GAD) antibody
timeFrame: Baseline (before the start of immunotherapy)
measure: Blood level of anti-glutamic acid decarboxylase (GAD) antibody
timeFrame: 3 months after baseline
measure: Blood level of anti-glutamic acid decarboxylase (GAD) antibody
timeFrame: 6 months after baseline
Secondary outcomes:
Other outcomes:
Locations:
city: Brussels
country: Belgium
facility: C.H.U. Saint-Pierre
city: Brussels
country: Belgium
facility: CHU Brugmann
city: Brussels
country: Belgium
facility: HUB - Institut Jules Bordet
Study officials:
affiliation: CHU Brugmann
name: Jeroen de Filette, MD
role: STUDY_DIRECTOR
References: