ROMANCE: "Irinotecan Plus Cetuximab Rechallenge Versus Trifluridine/Tipiracil Plus Bevacizumab in Molecularly Selected Metastatic Colorectal Cancer"

Inclusion Criteria

• •1. Male or female aged ≥18 years
• •2. Eastern Cooperative Oncology Group Performance Status (ECOG-PS) ≤1
• •3. Diagnosis of histologically or cytologically confirmed colorectal cancer.
• •4. At least one measurable lesion according to RECIST1.1
• •5. KRAS/NRAS/BRAFV600E wt status of primary CRC or related metastasis (local laboratory assessment).
• •6. Progression to previous first-line anti-EGFR-containing therapy producing at least a partial response ≥ 6 months.
• •7. Received and progressed to an anti-EGFR and irinotecan free second-line treatment.
• •8. Have an anti-EGFR free interval of at least 4 months.
• •9. Refractory to previous 5-fluorouracil/capecitabine, irinotecan, oxaliplatin, bevacizumab.
• •10. RAS/BRAF/EGFR/PIK3CAex20/MAP2K1/MET WT and HER2 not amplified ctDNA at FoundationOne CDx test at baseline.
• •11. Life expectancy of at least 3 months.
• •12. 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).
• •13. 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).
• •14. Adequate renal function defined by an estimated creatinine clearance \> 30 mL/min according to the Cockcroft-Gault formula (or local institutional standard method).
• •15. No contraindication to the study drugs.
• •16. No prior treatment with trifluridine/tipiracil.
• •17. Women of childbearing potential\* must have a negative blood pregnancy test at thescreening visit. Subjects and their partners must be willing to avoid pregnancy during the trial.
• •\*A woman is considered of childbearing potential (WOCBP), i.e. fertile, following menarche and until becoming post-menopausal unless permanently sterile. Permanent sterilisation methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy.
• •18. Women of childbearing potential, or male, must agree to use adequate contraception (e.g., abstinence, intrauterine device, oral contraceptive, or double-barrier method), during the study and until at least 6 months after last dose of study treatment administration, based on the judgment of the Investigator or a designated associate.
• •19. Will and ability to comply with the protocol.
• •20. Signed informed consent obtained before screening.