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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Solid Cancers; Solid Tumor Malignancies
• Intervention / Treatment: Other: Bloodsampling; Other: Pharyngeal swab sampling; Other: Cuteanous swab sampling; Other: Stools sample collection

• Study Type: Interventional
• Enrollment (Estimated): 160
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Nausicaa Malissen, dr; Phone Number: 33 0491435817; Email: promotion.interne@ap-hm.fr

Study Locations

• France
  • Marseille, France
    • Assistance Publique Hopitaux de Marseille
    • Contact: Nausicaa Malissen, dr; Phone Number: 33 0491435817; Email: promotion.interne@ap-hm.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Blood, Throat and skin swabs and Stool additional samples; Blood, Throat and skin swabs and Stool additional samples are collected in parallel of treatment administration throughout visits 1 to 4.

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).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Identification of a predictive baseline signature who maximize the rate of prediction of severe iRAE	The primary endpoint is the identification of a predictive baseline signature who maximize the rate of prediction of severe iRAE among patients who had a severe iRAE (iRAE + patients) and minimize the rate of prediction of severe iRAE among patients who had not a severe iRAE (iRAE- patients), we choose a minimum of 70% of prediction in iRAE + population and a maximum of 15% of prediction in iRAE- population.	From enrollment to the end of following after 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assesment of safety according to NCI-CTCAE v5.0 criteria		From enrollment to the end of following after 12 months
Identification of signatures for severe iRAEs	Predictive performance of baseline + T1 signatures for severe iRAEs	From enrollment to the end of following after 12 months
Identification of signatures for organ-specific severe iRAEs	Predictive performance of baseline signatures for organ-specific severe iRAEs using the same performance thresholds.	From enrollment to the end of following after 12 months
Identification of signatures for organ-specific severe iRAEs at baseline and T1	Predictive performance of baseline + T1 signatures for organ-specific severe iRAEs.	From enrollment to the end of following after 12 months
Identification of signatures for severe iRAEs in patients receiving anti-PD(L)1 monotherapy.	Performance of baseline signatures for severe iRAEs in patients receiving anti-PD(L)1 monotherapy.	From enrollment to the end of following after 12 months
Identification of signatures in patients receiving combination immunotherapy		From enrollment to the end of following after 12 months
Identification of baseline signatures for each specific immunotherapy class.		From enrollment to the end of following after 12 months
Comparison of predictive signatures between responders and non-responders (RECIST 1.1).		From enrollment to the end of following after 12 months
Rate of biological parameter variation between severe and non-severe iRAE patients		From enrollment to the end of following after 12 months
Assessment of PRO-CTCAE	NCI-PRO-CTCAE (Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events): which is a 81-item instruments designed to measure symptoms and side effects for patients through treatment for their cancer. Items are constructed on a 5-point Likert scale with the following response options: 1 "Not at all" / 2 "A little" / 3 "Quite a bit" / 4 "severe" / 5 "Extremely severe".	From enrollment to the end of following after 12 months
Evaluation of quality of life via EORTC QLQ-C30 questionnaire	EORTC QLQ-C30 : European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire, which is a 30-item instrument designed to measure quality of life in all cancer patients. 28 items are constructed on a 4-point Likert scale with the following response options: 1 "Not at all" / 2 "A little" / 3 "Quite a bit" / 4 "A lot." The last two items are constructed on a 7-point response scale. These two items assess the patient's physical condition and overall quality of life, respectively, with response 1 corresponding to a "very poor" condition and response 7 to an "excellent".	From enrollement to the end of following after 12 months
Evaluation of quality of life via EQ-5D-5L questionnaire	EQ-5D-5L, which is descriptive system EuroQol comprises five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems and extreme problems. Scale frome 1 to 100, where 0 is the worst possible condition and 100 is the best.	From enrollement to end of the following after 12 months

Collaborators and Investigators

• Sponsor: Assistance Publique Hopitaux De Marseille

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2026
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): January 1, 2028

Study Registration Dates

• First Submitted: July 21, 2025
• First Submitted That Met QC Criteria: September 17, 2025
• First Posted (Actual): September 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 13, 2026
• Last Update Submitted That Met QC Criteria: March 11, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Immune checkpoint inhibitor; immuno-induced adverse events; baseline predictive signature
• Other Study ID Numbers: RCAPHM25_0294; 2025-A01531-48 (Other Identifier: IDRCB)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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