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

November 25, 2025 updated by: Iñigo Les Bujanda, Hospital Universitario Araba

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

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Observational

Enrollment (Estimated)

300

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Spain
    • Navarre
      • Pamplona, Navarre, Spain, 31008

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

ICI cohort: Patients in the ICI cohort will be recruited from the Medical Oncology outpatient clinics of the participating hospitals. All patients diagnosed with a solid neoplasm eligible for treatment with ICIs will be considered for inclusion, using consecutive case sampling.

SAD cohort: Patients in the SAD cohort will be recruited in the outpatient clinics of the HUN Internal Medicine Service's SAD Unit, using consecutive case sampling.

Description

ICI cohort:

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.

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:

Inclusion Criteria:

  • 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 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
ICI cohort
Patients with cancer treated with immune checkpoint inhibitors
Drug: Immune Checkpoint Inhibitors
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Occurrence of immune-related adverse event
Time Frame: 48 weeks
any symptom, sign, syndrome, or disease caused by an immune-activating mechanism during the administration of an ICI once other causes such as an infectious disease or tumor progression have been ruled out.
48 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Hospital Universitario Araba

Collaborators

Hospital Donostia
Hospital Galdakao-Usansolo
Hospital of Navarra
Hospital San Pedro de Logroño
Consorci Sanitari del Maresme. Hospital Universitari de Mataró

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 8, 2024

Primary Completion (Estimated)

December 1, 2026

Study Completion (Estimated)

December 1, 2026

Study Registration Dates

First Submitted

November 18, 2025

First Submitted That Met QC Criteria

November 18, 2025

First Posted (Estimated)

November 25, 2025

Study Record Updates

Last Update Posted (Estimated)

December 3, 2025

Last Update Submitted That Met QC Criteria

November 25, 2025

Last Verified

November 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PI_2023/90

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • ICF

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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