Pan-tumor Neoadjuvant Basket Study of Immune Check-point Inhibition and Novel Immuno-oncology Combinations

Inclusion Criteria:

1. Signed written informed consent

2. Patients at least 18 years of age

3. Non-metastatic, newly diagnosed dMMR and pMMR cancers either fitting within aspecific basket or in the "other" cohort (e.g. sarcoma, head and neck cancers, analcancer, esophageal SCC)

4. In case of pMMR tumors: no indication for neoadjuvant therapy according to standardof care, unless adjuvant treatment is considered a standard of care alternative;

5. Eligible for study biopsy

6. World health organization (WHO) performance status of 0 or 1

7. Screening laboratory tests must meet the following criteria and should be obtainedwithin 7 days prior to randomization/registration: White blood cell count (WBC > 2.0x 10^9/L, Absolute neutrophil count (ANC) > 1.5x10^9/L, platelets > 100 x 10^9/L,Hemoglobin > 5.0mmol/L. Transfusion is allowed to obtain an adequate hemoglobinlevel. Liver function tests: total bilirubin < 1.5 upper limit of normal (ULN) (except for subjects with Gilbert syndrome, who can have total bilirubin <3.0mg/dL); alkaline phosphatase <1.5 ULN; transaminases (ASAT/ALAT) <3 x ULN; Lactatedehydrogenase (LDH) < 1.5x ULN; Creatinine clearance (Cockcroft-Gault) of >45ml/min, Albumin > 3.0 g/dL

8. Women of childbearing potential (WOCBP)* must use appropriate method(s) ofcontraception. WOCBP should use an adequate method to avoid pregnancy for 20 weeksafter the last dose of investigational drug, Non-childbearing potential is definedas:

9. Postmenopausal: ≥ 50 years of age and has not had menses for greater than 1year.

10. Amenorrheic for ≥ 2 years without a hysterectomy and bilateral oophorectomy anda follicle- stimulating hormone value in the postmenopausal range uponpre-study(screening) evaluation.

11. Status is post-hysterectomy, bilateral oophorectomy, or tubal ligation.

12. Women of childbearing potential must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24 hours prior tothe start of cycle 1 day 1

13. Men who are sexually active with WOCBP must use any contraceptive method with afailure rate of less than 1% per year. Men receiving the study treatment and who aresexually active with WOCBP (excluding azoospermic men) will be instructed to adhereto contraception for a period of 28 weeks after the last dose of investigationaldrug and are not allowed to donate sperm during that timeframe.

Exclusion Criteria:

1. Signs of distant metastases on imaging and physical examination

2. Clinical obstruction

3. Clinical symptoms or radiological suspicion of perforation

4. Previous treatment with immune checkpoint inhibitors including but not limited toanti-CTLA4 or anti-PD1

5. Prior chemotherapy for any cancer

6. Radiotherapy prior to or planned post-surgery radiotherapy for disease under study

7. Active malignancies other than disease under study within 3 years prior toinclusion, except for malignancies with a negligible recurrence rate (e.g. <10% in 5years)

8. Allergies and Adverse Drug Reaction:

9. History of allergy to study drug components

10. History of severe hypersensitivity reaction to any monoclonal antibody

11. Intercurrent illnesses, including but not limited to infections, unstable anginapectoris

12. Underlying medical conditions that, in the investigator's opinion, will make theadministration of the study drug hazardous or obscure the interpretation of toxicitydetermination of adverse events

13. Positive test for hepatitis B virus surface antigen (HBsAg) or hepatitis C virusribonucleic acid (HCV antibody) indicating acute or chronic infection

14. History of testing positive for human immunodeficiency virus (HIV) or known acquiredimmunodeficiency syndrome (AIDS)

15. Active autoimmune disease or a documented history of autoimmune disease, or othermedical conditions requiring systemic steroid or immunosuppressive medications,except for subjects with vitiligo, diabetes mellitus type 1, hypothyroidism due toautoimmune condition only requiring hormone replacement, psoriasis or resolvedchildhood asthma/atopy not requiring systemic treatment

16. Conditions requiring systemic treatment with either corticosteroids (> 10 mg dailyprednisone equivalents) or other immunosuppressive medications within 14 days ofstudy drug administration. Inhaled or topical steroids and adrenal replacement doses > 10 mg daily prednisone equivalents are permitted in the absence of activeautoimmune disease

17. Live vaccines in the 4 weeks prior to inclusion

18. Psychological, familial, sociological or geographical condition potentiallyhampering compliance with the study protocol and follow-up schedule

19. Current pregnancy or breastfeeding