TISLELIZUMAB for Non-small cell lung cancer|Colorectal cancer|Pancreatic cancer|Soft tissue sarcoma

Inclusion criteria

• {"criterion_text":"-Age ≥ 18 years,"}
• {"criterion_text":"-Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1,"}
• {"criterion_text":"-Subjects must have adequate organ function as indicated by the following laboratory values (obtained within 7 days prior to randomization): a) 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. b) International normalized ratio (INR) or prothrombin time (PT) ≤ 1.5 x upper limit of normal (ULN). c) Activated partial thromboplastin time (aPTT) ≤ 1.5 x ULN. d) Serum total bilirubin ≤ 1.5 x ULN (total bilirubin must be < 3 x ULN for patients with Gilbert's syndrome). e) Aspartate and alanine aminotransferase (AST and ALT) ≤ 3 x ULN f)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)"}
• {"criterion_text":"-Subjects with a social security in compliance with the French law relating to biomedical research (Article L.1121-11 of French Public Health Code),"}
• {"criterion_text":"-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,"}
• {"criterion_text":"-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)."}
• {"criterion_text":"-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.(...)The following methods are considered as unacceptable methods (non-exhaustive list): periodic abstinence (calendar, symptothermal, post-ovulation methods) and withdrawal (coitus interruptus)."}
• {"criterion_text":"-Completion of surgical and peri-operative treatments as per international guidelines"}
• {"criterion_text":"-Subject must have completed standard curative-intent therapy for minimum 2 months and maximum 5 months and must not have standard treatment at least 2 months before blood sampling for ctDNA analyses"}
• {"criterion_text":"-Patients must not have blood transfusion at least 3 months before blood sampling for ctDNA analyses"}
• {"criterion_text":"-Histology: TNM stage II-III NSCLC, Stage II-III colorectal cancer, stage I-III pancreatic cancer, grade 3 soft-tissue sarcoma,"}
• {"criterion_text":"-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,"}
• {"criterion_text":"-Subjects must have a valid (positive or negative) ctDNA test result prior to randomization,"}
• {"criterion_text":"-Subjects must not have had prior immunotherapy (anti-PD-1 or anti-PD-L1),"}
• {"criterion_text":"-No evidence of disease on imaging as per RECIST criteria 1.1,"}

Exclusion criteria

• {"criterion_text":"-Participation in another clinical trial with an investigational product during the last 2 to 5 months and while on study treatment"}
• {"criterion_text":"-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"}
• {"criterion_text":"-Treatment with therapeutic oral or IV antibiotics within 2 weeks prior to initiation of study treatment"}
• {"criterion_text":"-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,"}
• {"criterion_text":"-Significant cardiovascular disease, such as: • History of myocardial infarction, acute coronary syndromes or coronary angioplasty/stenting/bypass grafting within the past 6 months, o 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%"}
• {"criterion_text":"-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"}
• {"criterion_text":"-History of stroke or transient ischemic attack within 6 months prior to randomization"}
• {"criterion_text":"-Pregnant or breastfeeding women"}
• {"criterion_text":"-Subjects under guardianship or deprived of his liberty by a judicial or administrative decision or incapable of giving its consent."}
• {"criterion_text":"-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"}
• {"criterion_text":"-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: o 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 o 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 o Patients who received intranasal, inhaled, topical or local steroid injections (e.g., intra articular injection)"}
• {"criterion_text":"-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)"}
• {"criterion_text":"-Any prior Grade ≥3 immune-related adverse event (irAE) while receiving any previous immunotherapy agent, or any unresolved irAE > Grade 1."}
• {"criterion_text":"-Known intolerance the study drugs or any of their excipients"}
• {"criterion_text":"-Patients with prior allogeneic stem cell or solid organ transplantation"}
• {"criterion_text":"-Patients with confirmed EGFR 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). Similarly, patients with confirmed ALK rearrangements are also excluded, as adjuvant alectinib is recommended as a standard treatment for this molecular subtype"}
• {"criterion_text":"-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"}
• {"criterion_text":"-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)."}
• {"criterion_text":"-Patients who underwent major surgery within 28 days prior to inclusion or until the surgical wound is fully healed"}
• {"criterion_text":"-History of HIV infection"}
• {"criterion_text":"-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"}
• {"criterion_text":"-Active tuberculosis"}
• {"criterion_text":"-History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins"}

Primary endpoints

• {"endpoint_text":"-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.","definition_or_measurement_approach":"Defined as the time from randomization to relapse or death, whichever occurs first. DFS rate assessed at 12, 24, 48 and 60 months."}

Secondary endpoints

• {"endpoint_text":"-DFS for MRD (-) patients defined as the time from randomization to relapse or death, whichever occurs first.","definition_or_measurement_approach":"Defined as the time from randomization to relapse or death, whichever occurs first."}
• {"endpoint_text":"-OS defined as the time from randomization to death from any cause at 12, 24, 48 and 60 months.","definition_or_measurement_approach":"Overall survival: time from randomization to death from any cause; assessed at 12, 24, 48 and 60 months."}
• {"endpoint_text":"-Percentage of MRD (+) subjects minimum 2 months and maximum 5 months after completion of standard curative-intent therapy","definition_or_measurement_approach":"Proportion of subjects who are MRD positive within specified window after curative-intent therapy."}
• {"endpoint_text":"-Time from detection of MRD to relapse at imaging as documented per RECIST v1.1.","definition_or_measurement_approach":"Measured as time interval from MRD detection to imaging-confirmed relapse per RECIST v1.1."}
• {"endpoint_text":"-Percentage of subjects with MRD assessment failure.","definition_or_measurement_approach":"Proportion of subjects for whom MRD assessment could not be completed or yielded invalid results."}
• {"endpoint_text":"-Time from baseline to detection of MRD (-) status in subjects who were MRD (+) at baseline","definition_or_measurement_approach":"Time-to-event from baseline to first documented MRD negative status in subjects MRD positive at baseline."}
• {"endpoint_text":"-Incidence and severity of treatment-emergent adverse events (TEAEs) including all non-serious and serious AEs. Percentage of subjects with: i) TEAEs leading to dose interruptions ii) TEAEs leading to discontinuation","definition_or_measurement_approach":"Safety assessed by incidence and grade of TEAEs per NCI-CTCAE v5; percentages of subjects with TEAEs leading to dose interruption or discontinuation."}
• {"endpoint_text":"-Scores from EORTC QLQ-C30 and EuroQol EQ-5D-5L questionnaires at baseline and at months 6, 12, 18 and 24.","definition_or_measurement_approach":"HRQoL measured using EORTC QLQ-C30 and EQ-5D-5L at specified timepoints."}
• {"endpoint_text":"-Incremental costs and QALY and ICER (€/QALY).","definition_or_measurement_approach":"Health economics outcomes: incremental cost, QALYs and ICER calculated in €/QALY."}
• {"endpoint_text":"-Percentage of MRD (+) subjects with complete MR rates at 6 and 12 months in subjects starting systemic therapy with tislelizumab or placebo after curative-intent therapy, defined as patients with undetectable ctDNA at the time of analysis","definition_or_measurement_approach":"Proportion of MRD(+) subjects achieving undetectable ctDNA at 6 and 12 months."}
• {"endpoint_text":"-Objective response rate and progression-free survival (PFS2) on the next line of therapy. (applicable for Arm A and B)","definition_or_measurement_approach":"ORR and PFS2 measured on subsequent therapy after relapse for participants from Arm A and B."}

France

Earliest CTIS Part Ii Submission Date

20-02-2024

Latest Decision Or Authorization Date

21-10-2025

Processing Time Days

609

Number Of Sites

13

Number Of Participants

717

Primary sponsor

Full Name

Institut Gustave Roussy

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

France