Interferon Signature in Cancer Patients Treated With Anti-CTLA-4 and Anti-PD-1/PD-L1 Therapies: A Multicenter, Prospective, Observational Cohort Study Comparing Cancer Patients and Non-Cancer Patients With Systemic Autoimmune Diseases

Status: Recruiting
Location: See location...
Intervention Type: Drug
Study Type: Observational
SUMMARY

This study aims to identify a way to predict the side effects that some people with cancer experience when receiving immunotherapy. These side effects, known as immune-related adverse events (irAEs), occur when the immune system mistakenly attacks healthy tissues, like certain autoimmune diseases. At present, clinicians lack reliable tests to determine who is most likely to develop these reactions. The goal of this study is to determine whether substances in the blood called interferons (IFNs) could serve as early warning markers. The study will include 300 people with cancer who are about to begin immunotherapy. To provide a meaningful comparison, the investigators will also enroll 40 individuals with autoimmune diseases such as lupus. Understanding how IFN levels differ between these groups may help clarify whether IFN patterns in cancer patients resemble those seen in autoimmune disease. Participants in both groups will be asked to provide small blood samples at predefined time points during their clinical care or treatment. Researchers will measure the levels of different IFN types in all samples to compare IFN levels between cancer patients and individuals with autoimmune diseases, and within the cancer group between patients who develop irAEs and those who do not. The long-term aim of the study is to develop a simple test that can help clinicians identify patients at higher risk of irAEs. Immune-related adverse events (irAEs) are a frequent complication in cancer patients treated with immune checkpoint inhibitors (ICIs), and they often resemble or exacerbate preexisting autoimmune diseases. Despite extensive research in the field, no validated predictive biomarkers of irAEs currently exist. Emerging evidence suggests that the IFN signature -long implicated in the pathogenesis of several systemic autoimmune diseases (SADs)- may also be upregulated in patients who develop ICI-induced irAEs, likely with substantial overlap among different IFN subtypes. Given these clinical and molecular similarities with SADs, it is plausible that IFN levels in peripheral blood carry predictive value for irAE risk, although the dominant IFN types in ICI-related toxicity remain unknown. The INTER-AUTENTIC project aims to determine whether baseline IFN levels and their dynamic changes, measured in peripheral blood using a dedicated panel, can predict the onset of irAEs in cancer patients receiving ICIs. Supported by the Medical Oncology departments of six university hospitals in Northern Spain, this multicenter, observational, prospective cohort study has been underway since 2021. Biobank samples have been collected from ICI-treated patients before treatment initiation, at protocol-defined time points, and at the moment of irAE diagnosis (ICI cohort). The study seeks to identify the IFN subtypes with the most pronounced differential expression between patients with and without irAEs, and to evaluate whether IFN levels enhance the predictive performance of a model incorporating other clinical variables potentially associated with immune-mediated toxicity. A sample size of 300 cancer patients has been estimated for this analysis. In addition, a second prospective cohort of 40 non-cancer patients with systemic lupus erythematosus, primary Sjögren's syndrome, systemic sclerosis, and/or idiopathic inflammatory myopathy (SAD cohort) will be included. Since IFNs play a well-established pathogenic role in these conditions, this cohort will allow characterization of the IFN signature at key follow-up points (baseline, remission, and disease flare) and comparison with the IFN profiles of ICI-treated patients, regardless of whether they develop irAEs.

Eligibility
Participation Requirements
Sex: All
Minimum Age: 18
Healthy Volunteers: f
View:

• Initiation of treatment with a single ICI or dual ICI therapy in accordance with current clinical guidelines;

• Patients who are treatment-naïve to ICIs; and

• Age ≥18 years.

• Meeting classification criteria for Systemic Lupus Erythematosus (SLE) (ACR/EULAR 2019), Primary Sjögren's Syndrome (pSS) (ACR/EULAR 2016), Systemic Sclerosis (SSc) (ACR/EULAR 2013), and/or Idiopathic Inflammatory Myopathy (IIM) (ACR/EULAR 2017).

• Age ≥18 years old.

Locations
Other Locations
Spain
Hospital Universitario de Navarra
RECRUITING
Pamplona
Time Frame
Start Date: 2024-01-08
Estimated Completion Date: 2026-12
Participants
Target number of participants: 300
Treatments
ICI cohort
Patients with cancer treated with immune checkpoint inhibitors
SAD cohort
Patients without cancer affected by systemic lupus erythematosus, primary Sjögren's syndrome, progressive systemic sclerosis, and/or idiopathic inflammatory myopathy.
Sponsors
Leads: Hospital Universitario Araba
Collaborators: Hospital Galdakao-Usansolo, Hospital of Navarra, Hospital Donostia, Consorci Sanitari del Maresme. Hospital Universitari de Mataró, Hospital San Pedro de Logroño

This content was sourced from clinicaltrials.gov

Similar Clinical Trials