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

Public Assistance-Hospitals of Marseille (AP-HM)

Status

Not yet enrolling

Conditions

Solid Tumor Malignancies

Solid Cancers

Treatments

Other: Pharyngeal swab sampling

Other: Stools sample collection

Other: Bloodsampling

Other: Cuteanous swab sampling

Study type

Interventional

Funder types

Other

Identifiers

NCT07192315

RCAPHM25_0294

2025-A01531-48 (Other Identifier)

Details and patient eligibility

About

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.

Enrollment

150 estimated patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Adults (≥18 years old)
Histologically or cytologically confirmed solid tumour malignancy
Patients are included in the study before their 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 treated at AP-HM in one of the CEPCM-affiliated departments.
Inclusions will be made such that at least 40% of included patients receive a combination of ICIs
Ability to comply with study procedures and follow-up schedule
The patient must have given free and informed consent and signed the consent form
Patient must have at least one measurable lesion according to RECIST 1.1 criteria
Patient who is a beneficiary or entitled beneficiary of a social security scheme

Exclusion criteria

Patients previously treated with ICIs
The patient's therapeutic plan includes targeted therapy, chemotherapy or any other systemic treatment in combination with ICI
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
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.
Patients of Adults without legal capacity
Patients in Health and Social Establishments
Persons in emergency situations
Persons deprived of their liberty
Absence or refusal of the informed consent