ICE Study: a Clinical Study of the Combination of Irinotecan Plus Cetuximab and Envafolimab as a Rechallenge Regimen in mCRC
This is a non-profit phase II, open, clinical study of the combination of irinotecan plus cetuximab and envafolimab as a rechallenge regimen, in pre-treated RAS/BRAF wild type metastatic colorectal cancer patients (according to liquid biopsy at baseline). Patients have been treated in front lines with irinotecan and cetuximab and had a clinical benefit (complete or partial response) from both of them, no matter whether they had treated by any PD-1 inhibitor before.
• 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) Efficacy of any front-line therapies containing cetuximab or irinotecan with a major response achieved (i.e. complete or partial response according to RECIST criteria v1.1)..
⁃ More than 2 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).