• Signed written informed consent before any trial-related procedure is undertaken that is not part of the standard patient management.

• Male or female subjects aged ≥ 18 years.

• Histologically proven diagnosis of colorectal adenocarcinoma.

• Diagnosis of metastatic disease.

• RAS (NRAS and KRAS exon 2,3 and 4) and BRAF wild-type in liquid biopsy at screening (according to NGS, Foundation/Roche).

• Efficacy of a first line therapy containing cetuximab with a major response achieved (i.e. complete or partial response according to RECIST criteria v1.1).

• Received a second line therapy.

• More than 4 months since the last dose of cetuximab administered in first line treatment before randomization.

• Measurable disease according to RECIST criteria v1.1.

⁃ ECOG PS of 0 to 1 at trial entry.

⁃ Estimated life expectancy of more than 12 weeks.

⁃ Adequate hematological function defined by white blood cell (WBC) count ≥ 2.5 × 109/L with absolute neutrophil count (ANC) ≥ 1.5 × 109/L, lymphocyte count ≥ 0.5 × 109/L, platelet count ≥ 100 × 109/L, and hemoglobin ≥ 9 g/dL (may have been transfused).

⁃ Adequate hepatic function defined by a total bilirubin level ≤ 1.5 × the upper limit of normal (ULN) range and AST and alanine aminotransferase (ALT) levels ≤ 2.5 × ULN for all subjects or AST and ALT levels ≤ 5 x ULN (for subjects with documented metastatic disease to the liver).

⁃ Adequate renal function defined by an estimated creatinine clearance \> 30 mL/min according to the Cockcroft-Gault formula (or local institutional standard method).

⁃ Effective contraception for both male and female subjects throughout the study and for at least 2 months after last study treatment administration if the risk of conception exists (Note: The effects of the trial drug on the developing human fetus are unknown; thus, women of childbearing potential and men must agree to use effective contraception, defined as 2 barrier methods, or 1 barrier method with a spermicide, an intrauterine device, or use of oral female contraceptive. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this trial, the treating physician should be informed immediately).

⁃ No prior immunotherapy