Post-surgical Liquid Biopsy-guided Treatment of Stage III and High-risk Stage II Colon Cancer Patients: the PEGASUS Trial

Inclusion Criteria:

* Pegasus trial written informed consent.
* Age ≥ 18 years.
* Histologically confirmed diagnosis of operable stage III or T4N0 stage II colon cancer located 12 cm from the anal verge by endoscopy and above the peritoneal reflection at surgery.
* Availability of plasma collected prior to surgery.
* Availability of the original FFPE tumor tissue.
* Acceptance to undergo at least all the interventional liquid biopsies.
* ECOG performance status 0-1.
* Normal organ functions. (as defined in section 9.3)
* Women with childbearing potential should complete a pregnancy test and be willing to use highly effective contraceptive methods.

Exclusion Criteria:- Patients having a MSI-H/MMRd tumor are excluded from the study (done according to standard clinical practice).

* History of another neoplastic disease, unless in remission for ≥ 5 years. Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (e.g. breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded.
* Had an incomplete diagnostic colonoscopy and/or polyps removal.
* Macroscopic or microscopic evidence of residual tumor (R1 or R2 resections). Patients should never have had any evidence of metastatic disease (including presence of tumor cells in the peritoneal lavage).
* Current or recent treatment with another investigational drug or participation in another investigational study
* Patient unable to comply with the study protocol owing to psychological, social or geographical reasons.
* Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the study.
* Inadequate contraception (male or female patients) if of childbearing or procreational potential.
* Clinically relevant cardiovascular disease.
* Acute or subacute intestinal occlusion or history of inflammatory bowel disease.
* Pre-existing neuropathy \> grade 1. Known grade 3 or 4 allergic reaction to any of the components of the treatment.
* Has a known DPD (DihydroPyrimidine Dehydrogenase) deficiency.
* Has a known Gilbert Syndrome or UGT1A1 homozygous \*28/\*28 germline variant.
* Has a known history of Human Immunodeficiency Virus (HIV). Note: No HIV testing is required.
* Has a known history of Hepatitis B (defined as Hepatitis B surface antigen \[HBsAg\] reactive) or known active Hepatitis C virus infection. Note: no testing for Hepatitis B and Hepatitis C is required unless mandated by local health authority.
* Has a known history of active TB (Bacillus Tuberculosis).