tislelizUMaB in canceR Patients With molEcuLar residuaL Disease

Inclusion Criteria:

1. Age ≥ 18 years.

2. Completion of surgical and peri-operative treatments as per internationalguidelines.

3. Subject must have completed standard curative-intent therapy (i.e: Surgery,Neoadjuvant and adjuvant therapy) for minimum 3 months and maximum 4.5 months priorto sending samples for MRD analyses.

4. Subject must not have standard treatment at least 3 weeks before blood sampling forctDNA analyses.

5. Patients must not have blood transfusion at least 3 months before blood sampling forctDNA analyses.

6. Histology: TNM stage II-III NSCLC, Stage II-III colorectal cancer, stage I-IIIpancreatic cancer, grade 3 limb or trunk wall soft-tissue sarcoma.

7. Subjects must have sufficient amount of archived primary tumor material for ctDNAand translational research analyses that will be conducted as defined in theprotocol.

8. Subjects must have a valid (positive or negative) ctDNA test result prior torandomization.

9. Subjects must not have had prior immunotherapy (anti-PD-1 or anti-PD-L1).

10. No evidence of disease on imaging as per RECIST criteria 1.1.

11. Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1.

12. Subjects must have adequate organ function as indicated by the following laboratoryvalues (obtained within 7 days prior to randomization):

13. 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 factorsupport ≤ 14 days before sample collection.

14. International normalized ratio (INR) or prothrombin time (PT) ≤ 1.5 x upperlimit of normal (ULN).

15. Activated partial thromboplastin time (aPTT) ≤ 1.5 x ULN.

16. Serum total bilirubin ≤ 1.5 x ULN (total bilirubin must be < 3 x ULN forpatients with Gilbert's syndrome).

17. Aspartate and alanine aminotransferase (AST and ALT) ≤ 3 x ULN.

18. Creatinine clearance ≥60 mL/min for participants with creatinine levels aboveinstitutional normal (≥ULN). Creatinine clearance should be calculated per theCockcroft-Gault formula (or local institutional standard method).

19. Subjects with a social security in compliance with the French law relating tobiomedical research (Article L.1121-11 of French Public Health Code).

20. Subjects should understand, sign, and date the written informed consent form priorto any protocol-specific procedures performed. Patient should be able and willing tocomply with study visits and procedures as per protocol.

21. Females of childbearing potential must be willing to use a highly effective methodof birth control for the duration of the trial, and ≥ 120 days after the last doseof the trial drug and have a negative serum pregnancy test ≤ 7 days of the firstdose of the trial drug. A barrier contraceptive method (e.g., condom) is alsorequired. A woman is considered of childbearing potential following menarche anduntil 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 monthbefore 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).

22. Nonsterile males must be willing to use a highly effective method of birth controlfor the duration of the study and for ≥ 120 days after the last dose of the trialdrug. A barrier contraceptive method (e.g., condom) is also required.

Exclusion Criteria:

1. Participation in another clinical trial with an investigational product during thelast 3 to 4.5 months and while on study treatment

2. Any condition which in the Investigator's opinion makes it undesirable for thesubject to participate in a clinical trial or which would jeopardize compliance withthe protocol,

3. Pregnant or breastfeeding women

4. Subjects under guardianship or deprived of his liberty by a judicial oradministrative decision or incapable of giving its consent.

5. Patients with confirmed EGFR (Epidermal Growth Factor Receptor ) exon 19 deletionsor exon 21 L858R substitutions are excluded from the study, due to the potentialbenefit from adjuvant osimertinib treatment, which represents a standard of care forthese genetic profiles in non-small cell lung cancer (NSCLC).

6. Treatment with systemic immunostimulatory agents (including but not limited tointerferons 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 forsystemic immunosuppressive medication during study treatment, with the followingexceptions:

• Patients who received acute, low-dose systemic immunosuppressant medication ora one-time pulse dose of systemic immunosuppressant medication (e.g., 48 hoursof corticosteroids as premedication for hypersensitivity reaction (e.g., CTscan premedication)) are eligible for the study after Principal investigatorapproval has been obtained

• Patients who received mineralocorticoids (e.g., fludrocortisone),corticosteroids for chronic obstructive pulmonary disease (COPD) or asthma, orlow-dose corticosteroids for orthostatic hypotension or adrenal insufficiencyare 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 previousimmunotherapy 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 oranticipation that such a live, attenuated vaccine will be required during the studyor within 5 months after the last dose of the study drugs (except anti-COVID-19vaccines)

12. Active or history of autoimmune disease or immune deficiency, with the exception ofhistory of treated autoimmune-related hypothyroidism and Type 1 diabetes mellitus oninsulin regimen

13. History of idiopathic pulmonary fibrosis (including pneumonitis or interstitial lungdisease), drug-induced pneumonitis, organizing pneumonia (i.e. bronchiolitisobliterans, 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 thesurgical wound is fully healed

15. History of HIV infection

16. Patients with active hepatitis infection (defined as having a positive hepatitis Bsurface antigen [HBsAg] test at screening) or hepatitis C. Patients with pasthepatitis B virus (HBV) infection or resolved HBV infection (defined as having anegative HBsAg test and a positive antibody to hepatitis B core antigen [anti-HBc]antibody test) are eligible. Patients positive for hepatitis C virus (HCV) antibodyare 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 tochimeric 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, orsevere pneumonia

20. Treatment with therapeutic oral or IV antibiotics within 2 weeks prior to initiationof study treatment

21. Significant cardiovascular disease, such as:

• History of myocardial infarction, acute coronary syndromes or coronaryangioplasty/stenting/bypass grafting within the past 6 months,

• Congestive Heart Failure (CHF) NYHA class III or IV or history of CHF NYHAclass III or IV, unless an echocardiogram or multi-gated acquisition scanperformed within 3 months day 1 reveals a left ventricular ejection fraction ≥ 55%

22. Uncontrolled hypertension defined by systolic pressure > 150 and/or diastolicpressure > 110 mmHg, with or without anti-hypertensive medication. Patients withinitial blood pressure elevations are eligible if initiation or adjustment ofanti-hypertensive medication lowers blood pressure to meet entry criteria

23. History of stroke or transient ischemic attack within 6 months prior torandomization