Trial Title:
tislelizUMaB in canceR Patients With molEcuLar residuaL Disease
NCT ID:
NCT06332274
Condition:
Cancer
Lung Cancer
Colo-rectal Cancer
Pancreas Cancer
Soft Tissue Sarcoma
Conditions: Official terms:
Sarcoma
Pancreatic Neoplasms
Tislelizumab
Study type:
Interventional
Study phase:
Phase 3
Overall status:
Not yet recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Intervention model description:
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.
Primary purpose:
Treatment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Intervention:
Intervention type:
Drug
Intervention name:
Tislelizumab
Description:
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 group label:
Arm A. MRD(+) - Tislelizumab treatment
Intervention type:
Other
Intervention name:
Blood sampling
Description:
Blood sampling for analyses of MRD (Molecular Residual Disease)
Arm group label:
Arm A. MRD(+) - Tislelizumab treatment
Arm group label:
Arm B. MRD(+) - placebo treatment
Arm group label:
Arm C. MRD(-) - De-escalated follow-up
Arm group label:
Arm D. MRD(-) - De-escalated follow-up
Intervention type:
Drug
Intervention name:
Placebo
Description:
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 group label:
Arm B. MRD(+) - placebo treatment
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(-)].
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Age ≥ 18 years,
2. Completion of surgical and peri-operative treatments as per international guidelines
3. Subject must have completed standard curative-intent therapy for minimum 3 months
and maximum 4.5 months, and must not have standard treatment at least 3 weeks before
blood sampling for ctDNA analyses
4. Patients must not have blood transfusion at least 1 week before blood sampling for
ctDNA analyses
5. 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,
6. 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,
7. Subjects must have a valid (positive or negative) ctDNA test result prior to
randomization,
8. Subjects must not have had prior immunotherapy (anti-PD-1 or anti-PD-L1),
9. No evidence of disease on imaging as per RECIST criteria 1.1,
10. Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1,
11. Subjects must have adequate organ function as indicated by the following laboratory
values (obtained within 7 days prior to randomization):
1. Absolute neutrophil count (ANC) ≥ 1.5 x 109/L, platelets ≥ 100 x 109/L,
haemoglobin ≥90 g/L. Note: Patients must not have required a blood transfusion
or growth factor support ≤ 14 days before sample collection.
2. International normalized ratio (INR) or prothrombin time (PT) ≤ 1.5 x upper
limit of normal (ULN).
3. Activated partial thromboplastin time (aPTT) ≤ 1.5 x ULN.
4. Serum total bilirubin ≤ 1.5 x ULN (total bilirubin must be < 3 x ULN for
patients with Gilbert's syndrome).
5. Aspartate and alanine aminotransferase (AST and ALT) ≤ 3 x ULN
6. Creatinine clearance ≥60 mL/min for participants with creatinine levels above
institutional normal (≥ULN). Creatinine clearance should be calculated per the
Cockcroft-Gault formula (or local institutional standard method)
12. Subjects with a social security in compliance with the French law relating to
biomedical research (Article L.1121-11 of French Public Health Code),
13. Subjects should understand, sign, and date the written informed consent form prior
to any protocol-specific procedures performed. Patient should be able and willing to
comply with study visits and procedures as per protocol,
14. Females of childbearing potential must be willing to use a highly effective method
of birth control for the duration of the trial, and ≥ 120 days after the last dose
of the trial drug and have a negative serum pregnancy test ≤ 7 days of the first
dose of the trial drug. A barrier contraceptive method (e.g., condom) is also
required. A woman is considered of childbearing potential following menarche and
until becoming post-menopausal (≥ 12 months of non-therapy-induced amenorrhea)
unless permanently sterile. Permanent sterilization methods include hysterectomy,
bilateral oophorectomy and bilateral salpingectomy with surgery at least 1 month
before the first dose of study drug or confirmed by follicle stimulating hormone
(FSH) test >40 mIU/mL and estradiol <40 pg/mL (<140 pmol/L).
15. Nonsterile males must be willing to use a highly effective method of birth control
for the duration of the study and for ≥ 120 days after the last dose of the trial
drug. A barrier contraceptive method (e.g., condom) is also required.
Exclusion Criteria:
1. Participation in another clinical trial with an investigational product during the
last 3 to 4.5 months and while on study treatment
2. 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,
3. Pregnant or breastfeeding women
4. Subjects under guardianship or deprived of his liberty by a judicial or
administrative decision or incapable of giving its consent.
5. 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).
6. 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
7. 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)
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 28 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
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Gustave Roussy
Address:
City:
Villejuif
Zip:
94800
Country:
France
Start date:
May 2024
Completion date:
April 2029
Lead sponsor:
Agency:
Gustave Roussy, Cancer Campus, Grand Paris
Agency class:
Other
Collaborator:
Agency:
BeiGene
Agency class:
Industry
Collaborator:
Agency:
C2i Genomics
Agency class:
Industry
Source:
Gustave Roussy, Cancer Campus, Grand Paris
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06332274
