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

NCT07249060 | Recruiting DMC

• 1 other identifier: PI_2023/90
• Study Type: observational
• Target: 300
• Locations: 1 country
• Sites: 1

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; Sjogren Syndrome; Systemic Sclerosis (SSc); Inflammatory Myopathies; Solid Tumors; Lupus Erythematosus, Systemic

Keywords

Immune Checkpoint Inhibitors; Adverse events; Biomarkers; Predictive; Prospective Studies; Immune System

Outcome Measures

Primary Outcomes (1)

• Occurrence of immune-related adverse event

  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

Study Arms (2)

ICI cohort

Patients with cancer treated with immune checkpoint inhibitors

Drug: 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.

Interventions

Immune Checkpoint Inhibitors DRUG

Administration of immune checkpoint inhibitors according to protocol

ICI cohort

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

• 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.

You may not qualify if:

• 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:
• 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.
• 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.

Sponsors & Collaborators

• Hospital Galdakao-Usansolo: collaborator
• Hospital San Pedro de Logroño: collaborator
• Consorci Sanitari del Maresme. Hospital Universitari de Mataró: collaborator
• Hospital Donostia: collaborator
• Hospital Universitario Araba: lead
• Hospital of Navarra: collaborator

Study Sites (1)

Hospital Universitario de Navarra

Pamplona, Navarre, 31008, Spain

RECRUITING

Related Publications (17)

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• Fernandez-Ruiz R, Niewold TB. Type I Interferons in Autoimmunity. J Invest Dermatol. 2022 Mar;142(3 Pt B):793-803. doi: 10.1016/j.jid.2021.11.031. Epub 2022 Jan 10.

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• Coukos A, Vionnet J, Obeid M, Bouchaab H, Peters S, Latifyan S, Wicky A, Michielin O, Chtioui H, Moradpour D, Fasquelle F, Sempoux C, Fraga M. Systematic comparison with autoimmune liver disease identifies specific histological features of immune checkpoint inhibitor-related adverse events. J Immunother Cancer. 2022 Oct;10(10):e005635. doi: 10.1136/jitc-2022-005635.

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• Salem JE, Bretagne M, Abbar B, Leonard-Louis S, Ederhy S, Redheuil A, Boussouar S, Nguyen LS, Procureur A, Stein F, Fenioux C, Devos P, Gougis P, Dres M, Demoule A, Psimaras D, Lenglet T, Maisonobe T, De Chambrun MP, Hekimian G, Straus C, Gonzalez-Bermejo J, Klatzmann D, Rigolet A, Guillaume-Jugnot P, Champtiaux N, Benveniste O, Weiss N, Saheb S, Rouvier P, Plu I, Gandjbakhch E, Kerneis M, Hammoudi N, Zahr N, Llontop C, Morelot-Panzini C, Lehmann L, Qin J, Moslehi JJ, Rosenzwajg M, Similowski T, Allenbach Y. Abatacept/Ruxolitinib and Screening for Concomitant Respiratory Muscle Failure to Mitigate Fatality of Immune-Checkpoint Inhibitor Myocarditis. Cancer Discov. 2023 May 4;13(5):1100-1115. doi: 10.1158/2159-8290.CD-22-1180.

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Biospecimen

Retention: SAMPLES WITH DNA

The specific types of biospecimens that will be retained are serum and buffy coat. * Serum: Six aliquots of 500 μL will be processed and stored from each sample at every collection time point. * Buffy Coat: Two tubes of buffy coat will be retained from each sample (one tube will contain RNAlater for subsequent RNA isolation); however, this specific biospecimen will only be processed and collected during the V1, V5, and V7 treatment cycles. All collected samples will be kept frozen at -80°C and stored in a coded manner to maintain confidentiality and sample integrity for future approved research.

MeSH Terms

Conditions

Lupus Erythematosus, Systemic; Sjogren's Syndrome; Scleroderma, Systemic; Myositis

Interventions

Immune Checkpoint Inhibitors

Condition Hierarchy (Ancestors)

Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Arthritis, Rheumatoid; Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Xerostomia; Salivary Gland Diseases; Mouth Diseases; Stomatognathic Diseases; Dry Eye Syndromes; Lacrimal Apparatus Diseases; Eye Diseases; Skin Diseases; Muscular Diseases; Neuromuscular Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Antineoplastic Agents, Immunological; Antineoplastic Agents; Therapeutic Uses

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 48 Weeks
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Iñigo Les Bujanda

Study Record Dates

• First Submitted: November 18, 2025
• First Posted: November 25, 2025
• Study Start: January 8, 2024
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: December 3, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF

Locations

ES (1)