TislelizUMaB In CanceR Patients With MolEcuLar ResiduaL Disease

Study Overview

tislelizUMaB in canceR Patients With molEcuLar residuaL Disease

Numerous studies have shown that even when imaging does not reveal the presence of cancer cells, traces of tumor DNA (i.e. originating from cancer cells) can be detected in the blood of certain patients: this is called molecular residual disease (MRD). When such traces are detected (we speak of MRD+ status), the risk of relapse is much higher than when there is no circulating tumor DNA (MRD - status). Given the success of immunotherapy in treating patients with metastatic disease in a variety of tumor types, there is enormous enthusiasm for expanding the use of immunotherapy to people with cancer at an early stage. UMBRELLA is a biology-driven trial designed to study the impact of systemic treatment with tislelizumab monotherapy after detection of MRD+ status after completion of surgery and perioperative treatments in patients with cancer of a solid tumor. Residual disease (MRD) will be determined by optimized detection and precise monitoring of circulating tumor DNA, enabling early detection of recurrence and disease monitoring, including in patients without MRD [MRD(-)].

N/A

Cancer
Lung Cancer
Colo-rectal Cancer
Pancreas Cancer
Soft Tissue Sarcoma

DRUG: Tislelizumab
OTHER: Blood sampling
DRUG: Placebo

2023-503316-33-00
2023/3720 (OTHER Identifier) (OTHER: CSET number)

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2024-02-29	Results First Submitted N/A	Last Update Submitted that met QC Criteria 2025-05-07
First Submitted that Met QC Criteria 2024-03-25	Results First Submitted that Met QC Criteria N/A	Last Update Posted (ACTUAL) 2025-05-13
First Posted (ACTUAL) 2024-03-27	Results First Posted N/A	Last Verified 2025-05

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Randomized

Interventional Model:
Parallel

Masking:
Quadruple

Arms and Interventions

Participant Group/Arm	Intervention/Treatment
EXPERIMENTAL: Arm A. MRD(+) - Tislelizumab treatment Systemic treatment with tislelizumab monotherapy at the recommended dose of 400 mg administered intravenously every 6 weeks for a maximum of 9 cycles and followed-up as per standard of care (clinical examination plus imaging every 3 months the first year	DRUG: Tislelizumab Formulation : 100 mg of antibody in 10 mL of isotonic solution (25 mM citrate buffer, 15 mM L-histidine/histidine hydrochloride, 190 mM trehalose-dihydrate, and 0.02% polysorbate 20 at pH 6.5) in a single-use vial. Dose Regimen: Tislelizumab 400 mg every OTHER: Blood sampling Blood sampling for analyses of MRD (Molecular Residual Disease)
PLACEBO_COMPARATOR: Arm B. MRD(+) - placebo treatment Control arm for MRD (+) subjects who will be administered with placebo instead of tislelizumab	OTHER: Blood sampling Blood sampling for analyses of MRD (Molecular Residual Disease) DRUG: Placebo Pharmaceutical form : Solvent IV bags used for dilution of tislelizumab (for example: "CHLORURE DE SODIUM FRESENIUS 0,9 %, solution injectable") Dose Regimen: every 6 weeks (Q6W) for a maximum of 9 cycles, on the first day of each cycle, in IV.
EXPERIMENTAL: Arm C. MRD(-) - De-escalated follow-up De-escalated follow-up: clinical examination plus imaging every 6 months the first year and yearly the second year) with standard of care in addition to biobanking at M12 for subsequent ctDNA analyses.	OTHER: Blood sampling Blood sampling for analyses of MRD (Molecular Residual Disease)
OTHER: Arm D. MRD(-) - De-escalated follow-up Control arm for MRD (-) subjects , followed up as per standard of care (clinical examination plus imaging every 3 months the first year and every 6 months the second year) in addition to biobanking at M12 for subsequent ctDNA analyses.	OTHER: Blood sampling Blood sampling for analyses of MRD (Molecular Residual Disease)

Primary Outcome Measures	Measure Description	Time Frame
Efficacy of tislelizumab compared to placebo as measured by DFS (Disease-free survival)	DFS for MRD (+) patients defined as the time from randomization to relapse or death, whichever occurs first. DFS rate will also be assessed at 12 months, 24 months, 48 months and 60 months.	relapse/death assessed up to 60 months and at 12 months, 24 months, 48 months and 60 months.

Secondary Outcome Measures	Measure Description	Time Frame
Estimation of DFS in subjects without MRD	DFS for MRD (-) patients defined as the time from randomization to relapse or death, whichever occurs first.	relapse/death assessed up to 60 months
Estimation of overall survival (OS)		12, 24, 48 and 60 months
Percentage of MRD (+) subject's completion of standard curative-intent therapy		1 year after the end of enrollment
Time between detection of MRD and detection of relapse at imaging.	As documented per RECIST v1.1	1 year after the end of enrollment
Percentage of subjects with MRD assessment failure.		1 year after the end of enrollment
Estimation of the time to become MRD (-) for MRD(+) patients	Time from baseline to detection of MRD (-) status in subjects who were MRD (+) at baseline	1 year after the end of enrollment
Evaluation of Health-Related Quality of Life (QLQ) by QLQ-C30	Scores from EORTC QLQ-C30 (Quality of Life Questionnaire)	Baseline and at months 6, 12, 18 and 24.
Evaluation of Health-Related Quality of Life (QLQ) by EQ-5D-5L	Scores from EuroQol EQ-5D-5L questionnaire	Baseline and at months 6, 12, 18 and 24.
Cost effectiveness analysis: incremental cost		1 year after the end of enrollment
Cost effectiveness analysis: QALY	Quality-Adjusted Life Year	1 year after the end of enrollment
Cost effectiveness analysis: ICER	Incremental Cost-Effectiveness Ratio (€/QALY).	1 year after the end of enrollment

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Name: Antoine ITALIANO, MD

Phone Number: +33 (0)1 42 11 42 11

Email: antoine.italiano@gustaveroussy.fr

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

Patients who received acute, low-dose systemic immunosuppressant medication or a one-time pulse dose of systemic immunosuppressant medication (e.g., 48 hours of corticosteroids as premedication for hypersensitivity reaction (e.g., CT scan premedication)) are eligible for the study after Principal investigator approval has been obtained
Patients who received mineralocorticoids (e.g., fludrocortisone), corticosteroids for chronic obstructive pulmonary disease (COPD) or asthma, or low-dose corticosteroids for orthostatic hypotension or adrenal insufficiency are eligible for the study
Patients who received intranasal, inhaled, topical or local steroid injections (e.g., intra articular injection) 8. Any prior Grade ≥3 immune-related adverse event (irAE) while receiving any previous immunotherapy agent, or any unresolved irAE > Grade 1. 9. Known intolerance the study drugs or any of their excipients 10. Patients with prior allogeneic stem cell or solid organ transplantation 11. Administration of a live, attenuated vaccine within 4 weeks prior to enrolment or anticipation that such a live, attenuated vaccine will be required during the study or within 5 months after the last dose of the study drugs (except anti-COVID-19 vaccines) 12. Active or history of autoimmune disease or immune deficiency, with the exception of history of treated autoimmune-related hypothyroidism and Type 1 diabetes mellitus on insulin regimen 13. History of idiopathic pulmonary fibrosis (including pneumonitis or interstitial lung disease), drug-induced pneumonitis, organizing pneumonia (i.e. bronchiolitis obliterans, cryptogenic organizing pneumonia), or evidence of active pneumonitis (history of radiation pneumonitis in the radiation field (fibrosis) is permitted). 14. Patients who underwent major surgery within 56 days prior to inclusion or until the surgical wound is fully healed 15. History of HIV infection 16. Patients with active hepatitis infection (defined as having a positive hepatitis B surface antigen [HBsAg] test at screening) or hepatitis C. Patients with past hepatitis B virus (HBV) infection or resolved HBV infection (defined as having a negative HBsAg test and a positive antibody to hepatitis B core antigen [anti-HBc] antibody test) are eligible. Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction (PCR) is negative for HCV RNA 17. Active tuberculosis. 18. History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins 19. Severe infection within 4 weeks prior to initiation of study treatment, including, but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia 20. Treatment with therapeutic oral or IV antibiotics within 2 weeks prior to initiation of study treatment 21. Significant cardiovascular disease, such as:

History of myocardial infarction, acute coronary syndromes or coronary angioplasty/stenting/bypass grafting within the past 6 months,
Congestive Heart Failure (CHF) NYHA class III or IV or history of CHF NYHA class III or IV, unless an echocardiogram or multi-gated acquisition scan performed within 3 months day 1 reveals a left ventricular ejection fraction ≥ 55% 22. Uncontrolled hypertension defined by systolic pressure > 150 and/or diastolic pressure > 110 mmHg, with or without anti-hypertensive medication. Patients with initial blood pressure elevations are eligible if initiation or adjustment of anti-hypertensive medication lowers blood pressure to meet entry criteria 23. History of stroke or transient ischemic attack within 6 months prior to randomization

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

BeiGene
Veracyte, Inc.

Investigators

Publications

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

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