tislelizUMaB in canceR Patients With molEcuLar residuaL Disease

NCT06332274 | Recruiting Phase 3

• 2 other identifiers: 2023-503316-33-002023/3720
• Study Type: interventional
• Target: 717
• Locations: 1 country
• Sites: 1

Brief Summary

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 \[MRD(-)\].

Conditions

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

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (11)

• Estimation of DFS in subjects without MRD

  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.

  1 year after the end of enrollment

• Percentage of subjects with MRD assessment failure.

  1 year after the end of enrollment

Study Arms (4)

Arm A. MRD(+) - Tislelizumab treatment

EXPERIMENTAL

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 and every 6 months the second year) in addition to ctDNA (circulating tumoral DNA) analysis at M6 and M12.

Drug: Tislelizumab; Other: Blood sampling

Arm B. MRD(+) - placebo treatment

PLACEBO COMPARATOR

Control arm for MRD (+) subjects who will be administered with placebo instead of tislelizumab

Other: Blood sampling; Drug: Placebo

Arm C. MRD(-) - De-escalated follow-up

EXPERIMENTAL

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

Arm D. MRD(-) - De-escalated follow-up

OTHER

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

Interventions

Tislelizumab DRUG

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 6 weeks (Q6W) for a maximum of 9 cycles, on the first day of each cycle, in IV.

Arm A. MRD(+) - Tislelizumab treatment

Blood sampling OTHER

Blood sampling for analyses of MRD (Molecular Residual Disease)

Arm A. MRD(+) - Tislelizumab treatment; Arm B. MRD(+) - placebo treatment; Arm C. MRD(-) - De-escalated follow-up; Arm D. MRD(-) - De-escalated follow-up

Placebo DRUG

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.

Arm B. MRD(+) - placebo treatment

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years.
• Completion of surgical and peri-operative treatments as per international guidelines.
• Subject must have completed standard curative-intent therapy (i.e: Surgery, Neoadjuvant and adjuvant therapy) for minimum 3 months and maximum 4.5 months prior to sending samples for MRD analyses.
• Subject must not have standard treatment at least 3 weeks before blood sampling for ctDNA analyses.
• Patients must not have blood transfusion at least 3 months before blood sampling for ctDNA analyses.
• Histology: TNM stage II-III NSCLC, Stage II-III colorectal cancer, stage I-III pancreatic cancer, grade 3 limb or trunk wall soft-tissue sarcoma.
• Subjects must have sufficient amount of archived primary tumor material for ctDNA and translational research analyses that will be conducted as defined in the protocol.
• Subjects must have a valid (positive or negative) ctDNA test result prior to randomization.
• Subjects must not have had prior immunotherapy (anti-PD-1 or anti-PD-L1).
• No evidence of disease on imaging as per RECIST criteria 1.1.
• Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1.
• Subjects must have adequate organ function as indicated by the following laboratory values (obtained within 7 days prior to randomization):
• Absolute neutrophil count (ANC) ≥ 1.5 x 109/L, platelets ≥ 100 x 109/L, haemoglobin ≥90 g/L. Note: Patients must not have required growth factor support ≤ 14 days before sample collection.
• International normalized ratio (INR) or prothrombin time (PT) ≤ 1.5 x upper limit of normal (ULN).
• Activated partial thromboplastin time (aPTT) ≤ 1.5 x ULN.

You may not qualify if:

• Participation in another clinical trial with an investigational product during the last 3 to 4.5 months and while on study treatment
• Any condition which in the Investigator's opinion makes it undesirable for the subject to participate in a clinical trial or which would jeopardize compliance with the protocol,
• Pregnant or breastfeeding women
• Subjects under guardianship or deprived of his liberty by a judicial or administrative decision or incapable of giving its consent.
• Patients with confirmed EGFR (Epidermal Growth Factor Receptor ) exon 19 deletions or exon 21 L858R substitutions are excluded from the study, due to the potential benefit from adjuvant osimertinib treatment, which represents a standard of care for these genetic profiles in non-small cell lung cancer (NSCLC).
• Treatment with systemic immunostimulatory agents (including but not limited to interferons or interleukin-2) within 4 weeks or five half-lives of the drug, whichever is shorter, prior to enrolment
• Treatment with systemic immunosuppressive medication (including, but not limited to, corticosteroids, cyclophosphamide, azathioprine, methotrexate and thalidomide) within 2 weeks prior to initiation of study treatment, or anticipation of need for systemic immunosuppressive medication during study treatment, with the following exceptions:
• 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)
• Any prior Grade ≥3 immune-related adverse event (irAE) while receiving any previous immunotherapy agent, or any unresolved irAE \> Grade 1.
• Known intolerance the study drugs or any of their excipients
• Patients with prior allogeneic stem cell or solid organ transplantation
• 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)
• 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

Sponsors & Collaborators

• Gustave Roussy, Cancer Campus, Grand Paris: lead
• BeiGene: collaborator
• Veracyte, Inc.: collaborator

Study Sites (1)

Gustave Roussy

Villejuif, Val De Marne, 94800, France

RECRUITING

MeSH Terms

Conditions

Neoplasms; Lung Neoplasms; Colonic Neoplasms; Pancreatic Neoplasms; Sarcoma

Interventions

tislelizumab; Blood Specimen Collection

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Lung Diseases; Respiratory Tract Diseases; Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Endocrine Gland Neoplasms; Pancreatic Diseases; Endocrine System Diseases; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Central Study Contacts

Antoine ITALIANO, MD

CONTACT

+33 (0)1 42 11 42 11; antoine.italiano@gustaveroussy.fr

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is a double-blinded, randomized, placebo-controlled, multi-center, national, Phase 3 biology-driven trial designed to investigate the impact of systemic treatment with tislelizumab or placebo following detection of MRD minimum 3 months and maximum 4.5 months after completion of curative-intent therapy.

Study Record Dates

• First Submitted: February 29, 2024
• First Posted: March 27, 2024
• Study Start: April 16, 2025
• Primary Completion (Estimated): April 1, 2029
• Study Completion (Estimated): April 1, 2030
• Last Updated: May 13, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)