Predicting Reactions and Effects of Drugs Immunotherapy and Complications Through Oncosafety (PREDICTO Clinical Study)

Overview

Immune Checkpoint Inhibitors (ICI) have revolutionized cancer therapy, providing unprecedented responses in a wide range of malignancies. However, they induced various immune-related adverse events (iRAE) that can be life-threatening. About 20% of patients treated with an ICI monotherapy, and up to 60% of patients treated with a combination of ICIs, experienced a severe iRAE. Most side effects are reversible if managed early, but can affect survival and quality of life, leading to treatment interruptions or hospitalization. Some of these irAEs, particularly those affecting hormonal functions, may be irreversible and persist even after treatment discontinuation. The development of predictive biomarkers of such toxicities is an unmet medical need. The variety of mechanisms involved in iRAE, and the lack of effective animal models, could probably explain why the topic remains largely unexplored. To date, some biomarkers predictive of the occurrence of iRAE, irrespective of the type of organ affected, have been identified by state-of-the-art techniques on small cohorts prior to treatment initiation, but none is individually robust enough to be used in daily practice. We hypothesize that a signature derived from the integrative analysis of various biological parameters (immunomonitoring, auto-immunity features, viral monitoring, microbiota monitoring, fragmentome analysis, pharmacokinetics, radiomics and genetics), available in routine hospital practice, could answer this question, and thus enable the development of specific prevention strategies The objectives are : Primary objective: Identify a baseline predictive signature for severe iRAE, irrespective of the type of organ affected. Secondary objectives: * Identify a predictive signature for severe iRAE including baseline and T1 data, irrespective of the type of organ affected. * Identify a baseline predictive signature for organ-specific severe iRAE. * Identify a predictive signature for organ-specific severe iRAE including baseline and T1 data. * Identify a baseline predictive signature for severe iRAE, irrespective of the type of organ affected, for patient receiving an anti-PD(L)1 in monotherapy. * Identify a baseline predictive signature for severe iRAE, irrespective of the type of organ affected, for patient receiving an anti-PD(L)1 in combination. * Identify a baseline predictive signature for severe iRAE, irrespective of the type of organ affected, for each specific immunotherapy received. * Compare the predictive signatures between responders and non-responders according to RECIST 1.1 in order not to overlook the influence of clinical response on the variability observed. * Describe the results obtained for each biological parameter between severe irAEs and non-severe irAEs patients. * Describe patient-reported outcomes and quality of life parameters.

Interventions

• Other Bloodsampling
  Blood will be sampled At Visit 1, 2, 3 and 4. For patients presenting immuno-induced adverse events (iRAEs), an additionnal visit V tox will be planned will a blood sampling.
• Other Pharyngeal swab sampling
  Pharyngeal swab will be sampled at visit 4 for patients without immuno-induced adverse events (iRAEs) Pharyngeal swab will be sampled at visit Tox for patients presenting immuno-induced adverse events (iRAEs)
• Other Cuteanous swab sampling
  Cuteanous swab will be sampled at visit 1, 2, 3 and 4 for patients without immuno-induced adverse events (iRAEs). Cuteanous swab will be sampled at visit 1, 2, 3 and tox for patients presenting immuno-induced adverse events (iRAEs).
• Other Stools sample collection
  Stools sample will be collected at visit 1, 2, 3 and 4 for patients without immuno-induced adverse events (iRAEs). Stools sample will be collected at visit 1, 2, 3 and tox for patients presenting immuno-induced adverse events (iRAEs).

Primary outcome measures

• Identification of a predictive baseline signature who maximize the rate of prediction of severe iRAE [Time frame: From enrollment to the end of following after 12 months]

Secondary outcome measures (12)

• Assesment of safety according to NCI-CTCAE v5.0 criteria [Time frame: From enrollment to the end of following after 12 months]
• Identification of signatures for severe iRAEs [Time frame: From enrollment to the end of following after 12 months]
• Identification of signatures for organ-specific severe iRAEs [Time frame: From enrollment to the end of following after 12 months]
• Identification of signatures for organ-specific severe iRAEs at baseline and T1 [Time frame: From enrollment to the end of following after 12 months]
• Identification of signatures for severe iRAEs in patients receiving anti-PD(L)1 monotherapy. [Time frame: From enrollment to the end of following after 12 months]
• Identification of signatures in patients receiving combination immunotherapy [Time frame: From enrollment to the end of following after 12 months]
• Identification of baseline signatures for each specific immunotherapy class. [Time frame: From enrollment to the end of following after 12 months]
• Comparison of predictive signatures between responders and non-responders (RECIST 1.1). [Time frame: From enrollment to the end of following after 12 months]
• Rate of biological parameter variation between severe and non-severe iRAE patients [Time frame: From enrollment to the end of following after 12 months]
• Assessment of PRO-CTCAE [Time frame: From enrollment to the end of following after 12 months]
• Evaluation of quality of life via EORTC QLQ-C30 questionnaire [Time frame: From enrollement to the end of following after 12 months]
• Evaluation of quality of life via EQ-5D-5L questionnaire [Time frame: From enrollement to end of the following after 12 months]

Eligibility criteria

Inclusion criteria

• Adult patient (≥18 years old)
• Patient presenting an histologically or cytologically confirmed solid tumour malignancy
• Patient scheduled to receive his/her first infusion of immunotherapy with anti-PD1, anti-PDL1, anti-CTLA4, anti-LAG3, alone or in combination, as part of standard care, in all validated solid oncology indications.
• Patient must have at least one measurable lesion according to RECIST 1.1 criteria
• Patient treated at AP-HM in one of the CEPCM-affiliated departments.
• Patient able to comply with study procedures and follow-up schedule
• Patient who has been informed about the study and signed the consent form
• Patient who is a beneficiary or entitled beneficiary of a social security scheme

Exclusion criteria

• Patient previously treated with ICIs
• Patient whose treatment plan includes targeted therapy, chemotherapy or any other systemic treatment in combination with ICI
• Patient included in a trial with an experimental molecule
• Patient has an active autoimmune disease or any other pathology requiring systemic corticosteroid therapy at more than 10 mg prednisone equivalent per day or any other immunosuppressive drug
• Patients with a history of organ transplantation, hematopathy or hematopoietic stem cell transplantation
• Patient with history or current evidence of any condition, therapy, laboratory abnormality, or other circumstance that might confound the results of the study or interfere with the participant's participation for the full duration of the study, such that it is not in the best interest of the participant to participate, in the opinion of the treating investigator.
• Patient in emergency situations, persons deprived of their liberty by judicial or administrative decision, adults subject to legal protection measures, or persons who are unable to give their consent, or pregnant or breastfeeding.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Other

Study locations

France · 1 center

• Assistance Publique Hôpitaux de marseille — Marseille

Identifiers

NCT: NCT07192315 · RCAPHM25_0294 · 2025-A01531-48

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗