MSI/dMMR tumors in perioperative setting

Korábbi kezelés

• E20. Recent hemorrhage (in the month before inclusion).
• E4. Concurrent active Hepatitis B (defined as Hepatitis B surface antigen [HBsAg] positive and/or detectable HBV DNA) or Hepatitis C virus (defined as anti-HCV Ab positive and detectable HCV RNA) infection).
• E7. Prior (non-infectious) pneumonitis requiring systemic corticosteroid therapy or current pneumonitis.
• E9. Receiving immunosuppressive therapy or having received corticosteroids (in dosing exceeding 10 mg daily of prednisone equivalent) within the last 2 months before inclusion.
• E12. Live vaccine within 30 days prior to the first dose of study drug. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette–Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (eg, FluMist®) are live attenuated vaccines and are not allowed

Más betegség

• E2. Metastatic disease (stage IV).
• E5. Active systemic autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg. thyroxine, insulin) is not considered a form of systemic treatment and is allowed.
• E6. Interstitial lung disease.
• E8. History of severe hypersensitivity to another monoclonal antibody.
• E10. Active infections.
• E13. Known history of active TB (Bacillus Tuberculosis).
• E14. Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the study.
• E17. Ongoing anti-cancer treatment for another cancer (to be discussed with the coordinator in case of hormone therapy).
• E18. Prior history of other malignancies (except for HNPCC or Lynch syndrome-related cancers) unless the subjects has been free of the disease for at least 2 years

Laborértékek

• E3. HIV positive with CD4 count under 400 cells/mm3 .

Egyéb

• E1. MSS/pMMR tumors.
• E19. Patient hospitalized at the moment of inclusion and treatment initiation (palliative care unit, retirement home … are considered as hospitals).
• E15. Pregnant or breastfeeding woman or patient expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 4 months after the last dose of study treatment.
• E16. Patient requiring tutorship or curatorship.

• I1. Age ≥ 18 years on the day of signing informed consent.
• I2. Histologically proven localized non-metastatic tumor included in one of the following cohorts: - Colorectal or rectal Cancer (cT3/T4 N0 M0 ou cT N+ M0) OR - Oesogastric (gastric, gastro-oesophageal or oesophageal) cancer (cT2 to cT4, N, M0) OR - Other tumor types (cT2 to cT4, N, M0) : small bowel adenocarcinoma (duodenum, jejunum, ileum)
• I3. MSI/dMMR established by immunohistochemistry (IHC) [MMR protein expression] and polymerase chain reaction (PCR) (or NextGeneration Sequencing (NGS)) [both techniques are required] and validated by coordinator's team. MMR and/or MSI tumors will be assessed using IHC with four antibodies (anti-MLH1, anti-MSH2, anti-MSH6 and anti-PMS2) and PCR (pentaplex panel is recommended: BAT-25, BAT-26, NR-21, NR-24, and NR-27) prior to screening. Loss of MLH1 and PMS2 / or MSH2 and MSH6 / or MSH6 alone / or PMS2 alone protein staining by IHC indicates dMMR, and tumor with ≥ 2 unstable markers analyzed on PCR proves MSI/dMMR. NGS will be accepted instead of PCR analysis.
• I4. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0 to 1 within 7 days prior to the inclusion.
• I5. Adequate bone-marrow, hepatic, and renal functions, within 10 days prior to the start of study treatment with: - Hemoglobin ≥ 9 g/dl or ≥ 5.6 mmol/l, neutrophils ≥ 1.0 x 109, platelets ≥ 100 x 109, - Creatinine ≤ 1.5 x ULN or calculated creatinine clearance ≥ 30 ml/min/1.73m² using either MDRD or CKD-EPI formula, - AST and ALT ≤ 3 x ULN, total bilirubin ≤ 1.5 ULN (or direct bilirubin ≤ ULN for participants with total bilirubin levels >1.5 × ULN), - INR or PT ≤ 1.5 × ULN unless participant is receiving anticoagulant therapy as long as PT or aPTT is within therapeutic range of intended use of anticoagulants.
• I6. Covered by a medical/health insurance.
• I7. Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures.
• I8. Patients of childbearing potential accepting to use effective contraceptive measures or abstain from heterosexual activity, for the course of the study through 4 months after the last dose of pembrolizumab MK-3475 adjuvant treatment or 6 months after adjuvant chemotherapy or being surgically sterile. Refer to Appendix 1 for approved methods of contraception.
• I9. Signed and dated IRB/IE approved informed consent form.