Autoantibodies in Treatment With Immune Checkpoint Inhibitors (AUTENTIC) (AUTENTIC)

Prediction of Immune-related Adverse Events Induced by Anti-CTLA4 and Anti-PD1/PDL1 Drugs by Means of a Battery of Autoantibodies. A Multicenter Prospective Observational Cohort Study

The aim of this study is to assess the effectiveness of a battery of autoantibodies to predict the occurrence of immune-related adverse events (irAEs) in patients with cancer who will be treated with immune checkpoint inhibitors (ICIs) per standard protocol.

Study Overview

• Status: Recruiting
• Conditions: Cancer; Metastatic Cancer; Solid Organ Cancer
• Intervention / Treatment: Drug: Treatment with immune checkpoint inhibitors.; Diagnostic test: Blood tests.

Detailed Description

Introduction: Treatment with ICIs is leading to a remarkable improvement in the prognosis of several types of cancer. However, the expansion of these drugs in the field of oncology is also causing the emergence of a large diversity of irAEs, whose optimal prevention and management are still to be clarified. Nowadays, there is a growing need for reliable and validated biomarkers to predict the occurrence of irAEs in patients treated with ICIs.

Purpose: To assess the effectiveness of a battery of autoantibodies available in a laboratory of autoimmunity to predict the occurrence of irAEs in patients with cancer who will be treated with ICIs per standard protocol.

Methods: A multicenter prospective observational cohort study was designed to include a total of 221 patients diagnosed with cancer amenable to treatment with ICIs. During a period of 48 weeks, patients will be controlled in the oncology outpatient clinics of five university hospitals with accredited experience in the management of immunotherapy. Immune-related adverse events will be defined and categorized according to CTCAE v. 5.0. Considering a proportion of irAEs and losses to follow-up of 25% and 5% respectively, a sample size of 221 patients was calculated to estimate an expected sensitivity of the autoantibody battery of 0.90 with a 95% confidence interval not lower than 0.75. All the participants will undergo ordinary blood tests at specific moments predefined per protocol and extraordinary blood tests at the time of the detection of an eventual irAE. Both ordinary and extraordinary samples will be frozen and stored in the biobank of each participating hospital in the form of serum and buffy coat. Once the whole cohort reaches the 24th week (intermediate analysis) and the 48th week (definitive analysis), all the samples will be centralized in the same autoimmunity laboratory for the determination of the autoantibody battery. A predictive model of irAEs will be constructed with the autoantibodies together with other potential risk factors of immune-mediated toxicity.

• Study Type: Observational
• Enrollment (Anticipated): 221

Contacts and Locations

Study Locations

• Spain
  • Álava
    • Vitoria, Álava, Spain, 01009
      • Recruiting
      • Hospital Universitario Araba

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 99 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

All patients diagnosed with cancer amenable to treatment with ICIs will be considered eligible. Potential candidates will be identified and consecutively included in the oncology outpatient clinics of five university hospitals in Spain.

Description

Inclusion Criteria:

1. Initiation of treatment with a single ICI or a combination of ICIs.
2. Acceptation of an informed consent.

Exclusion Criteria:

1. Life expectancy lower than 3 months from the initiation of treatment with ICIs.
2. Proven hypersensitivity or previous allergic anaphylactic reaction induced by a specific ICI.
3. Active autoimmune disease with severe involvement.
4. Eastern Cooperative Oncology Group (ECOG) performance status ≥ 3.
5. Ongoing immunosuppressive therapy: prednisone at doses >10 mg/day or equivalent (>1.5 mg/day of dexamethasone), and/or any dose of azathioprine, methotrexate, mycophenolate, cyclophosphamide, leflunomide, rituximab, anti-tumor necrosis factor drugs (infliximab, etanercept, adalimumab, golimumab), belimumab and abatacept.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

Patients treated with ICIs.; All enrolled patients must have been diagnosed with a cancer potentially treatable with ipilimumab, nivolumab, pembrolizumab, atezolizumab or avelumab, alone or in combination, per standard protocol.

Drug: Treatment with immune checkpoint inhibitors.; Treatment with approved immune checkpoint inhibitors, namely ipilimumab, nivolumab, pembrolizumab, atezolizumab and avelumab, alone or in combination, administered per standard protocol.; Diagnostic test: Blood tests.; Patients will undergo ordinary blood tests obtained at specific moments predefined per protocol and extraordinary blood tests at the time of the detection of an eventual irAE.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of irAEs.	An irAE was defined as any symptom, sign, syndrome or disease attributable to an immune activation mechanism during an ongoing treatment with an ICI or a combination of ICIs, provided that an infectious cause and/or tumor progression have been ruled out.	At 48 weeks from the initiation of ICIs.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
irAE-free survival.	Time in months from the initiation of therapy with ICIs until the occurrence of an irAE or until the date of the last follow-up.	At 24 weeks and at 48 weeks from the initiation of ICIs.
Progression-free survival.	Time in months from the initiation of therapy with ICIs until the date of proven tumor progression or until the date of the last follow-up.	At 24 weeks and at 48 weeks from the initiation of ICIs.
Overall survival.	Time in months from the initiation of therapy with ICIs until the date of patient's death or until the date of the last follow-up.	At 24 weeks and at 48 weeks from the initiation of ICIs.
Incidence of development of autoantibodies.	Positive conversion of the autoantibody battery after the initiation of therapy with ICIs.	At 24 weeks and at 48 weeks from the initiation of ICIs.

Collaborators and Investigators

• Sponsor: Hospital Universitario Araba
• Collaborators: Hospital Donostia; Hospital de Basurto; Complejo Hospitalario de Navarra; Hospital Galdakao-Usansolo

Study record dates

Study Major Dates

• Study Start (Actual): August 25, 2019
• Primary Completion (Anticipated): October 31, 2023
• Study Completion (Anticipated): December 31, 2023

Study Registration Dates

• First Submitted: March 6, 2019
• First Submitted That Met QC Criteria: March 7, 2019
• First Posted (Actual): March 8, 2019

Study Record Updates

• Last Update Posted (Actual): March 2, 2023
• Last Update Submitted That Met QC Criteria: February 28, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Keywords: Immune Checkpoint Inhibitors; Biomarkers; Autoantibodies; Immune-related Adverse Events
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Neoplastic Processes; Neoplasm Metastasis; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Immune Checkpoint Inhibitors
• Other Study ID Numbers: PI2018106 (EPA-SP)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: All collected IPD will be available for exploitation in future research projects. This statement also includes the availability of the study protocol, the statistical analysis plan, the informed consent form, the clinical study report and the analytic code.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No