Interferon Signature in Anti-CTLA-4 and Anti-PD-1/PD-L1-Treated Cancer Patients Compared With Systemic Autoimmune Disease Patients

NCT ID: NCT07249060

Last Updated: 2025-12-03

Basic Information

• Recruitment Status: RECRUITING
• Total Enrollment: 300 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2024-01-08
• Study Completion Date: 2026-12-31

Brief 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.

Conditions

Immune-Related Adverse Events; Lupus Erythematosus, Systemic; Sjogren Syndrome; Systemic Sclerosis (SSc); Inflammatory Myopathies; Solid Tumors

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

ICI cohort

Patients with cancer treated with immune checkpoint inhibitors

Immune Checkpoint Inhibitors

Intervention Type: DRUG

Administration of immune checkpoint inhibitors according to protocol

SAD cohort

Patients without cancer affected by systemic lupus erythematosus, primary Sjögren's syndrome, progressive systemic sclerosis, and/or idiopathic inflammatory myopathy.

No interventions assigned to this group

Interventions

Immune Checkpoint Inhibitors

Administration of immune checkpoint inhibitors according to protocol

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 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.

Exclusion Criteria

• Estimated mortality of less than 3 months from the start of treatment;
• Current combination therapy with chemotherapy, tyrosine kinase inhibitors, or other tumor-specific treatments;
• Contraindication to treatment with ICIs (documented hypersensitivity, severe active autoimmune disease, Eastern Cooperative Oncology Group [ECOG] ≥3);
• Ongoing immunosuppressive therapy, including prednisone at doses >10 mg/day or equivalent.

SAD cohort:

• Estimated mortality less than 3 months from the start of follow-up.
• Active immunosuppressive treatment, including prednisone at doses >10 mg/day or equivalent.
• Recent diagnosis (<1 year) of cancer, with the exception of non-melanoma skin cancer, or currently receiving active oncology-specific treatment.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hospital of Navarra

OTHER

Sponsor Role: collaborator

Hospital Galdakao-Usansolo

OTHER_GOV

Sponsor Role: collaborator

Hospital San Pedro de Logroño

OTHER

Sponsor Role: collaborator

Consorci Sanitari del Maresme. Hospital Universitari de Mataró

OTHER

Sponsor Role: collaborator

Hospital Donostia

OTHER

Sponsor Role: collaborator

Hospital Universitario Araba

OTHER

Sponsor Role: lead

Responsible Party

Iñigo Les Bujanda

Iñigo Les Bujanda

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Hospital Universitario de Navarra

Pamplona, Navarre, Spain

Site Status: RECRUITING

Countries

Spain

Facility Contacts

Iñigo Les, MD, PhD

Role: primary

inigo.les.bujanda@navarra.es

0034848429698

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Other Identifiers

PI_2023/90

Identifier Type: -

Identifier Source: org_study_id