cetuximab, irinotecan, toripalimab in ras/braf wild-type ultraselected right-sided colorectal cancer study

Conditions: Colorectal Cancer Metastatic

Summary: the objective of this clinical trial is to evaluate the efficacy and safety of cetuximab combined with pd-1 inhibitor and irinotecan in negative ultraselection ras/braf wild-type refractory right-sided metastatic colorectal cancer.

the present study focuses on exploring the effectiveness and safety of cetuximab combined with a pd-1 inhibitor and irinotecan in treating refractory, right-sided metastatic colorectal cancer (mcrc) patients who are negative ultraselected for ras/braf mutations. colorectal cancer ranks among the most prevalent digestive malignancies globally, with right-sided mcrc generally exhibiting poorer outcomes than left-sided cases. current treatment guidelines vary based on genetic mutations and tumor location, recommending cetuximab for left-sided ras/braf wild-type mcrc and alternative therapies for right-sided or mutated cases. despite limited clinical data on egfr inhibitors for right-sided mcrc, retrospective analyses suggest varying efficacy outcomes. the study aims to address these gaps by investigating cetuximab and pd-1 inhibitor combination therapy in this specific patient population, potentially enhancing treatment options for refractory mcrc.

Eligibility criteria:
inclusion criteria: * histologically confirmed colorectal adenocarcinoma. * primary tumor located in the right colon. * metastatic disease with at least one measurable lesion according to recist v1.1 criteria. * histologically tested as ras/braf v600e wild-type and negative ultraselected for mutations including: ras/braf v600e/pik3ca/pten/egfr (ecd), her2 and met amplification, and alk/ret/ntrk1 gene fusions. * patients who have progressed after previous treatments including bevacizumab, irinotecan, oxaliplatin, and 5-fluorouracil, with tumor progression occurring during or within 3 months after irinotecan treatment. * no prior treatment with anti-egfr or pd-1 antibodies. * normal hematological function (platelets \>90×10\^9/l; white blood cells \>3×10\^9/l; neutrophils \>1.5×10\^9/l). * serum bilirubin ≤1.5 times the upper limit of normal (uln), transaminases ≤5 times uln. * no ascites, normal coagulation function, albumin ≥35 g/l. * liver function classified as child-pugh grade a. * serum creatinine less than uln, or calculated creatinine clearance \>50 ml/min (using the cockcroft-gault formula). * at least one measurable lesion according to recist v1.1 criteria. * ecog performance status of 0-2. * expected survival \>3 months. * signed written informed consent. * willing and able to undergo follow-up until death or study completion or termination. exclusion criteria: * severe arterial thrombosis or ascites. * bleeding tendencies or coagulation disorders. * hypertensive crisis or hypertensive encephalopathy. * severe uncontrolled systemic complications such as infections or diabetes. * clinically significant cardiovascular diseases such as cerebrovascular accident (within 6 months prior to enrollment), myocardial infarction (within 6 months prior to enrollment), uncontrolled hypertension despite appropriate medication, unstable angina, congestive heart failure (nyha grade 2-4), or arrhythmias requiring medication. * history of or physical examination showing central nervous system diseases (e.g., primary brain tumor, uncontrolled epilepsy, any history of brain metastasis or stroke). * other malignancies within the past 5 years (except for basal cell carcinoma of the skin after curative surgery and/or carcinoma in situ of the cervix). * use of immunosuppressive drugs within 1 week before treatment, excluding nasal, inhaled, or other topical steroids or physiological doses of systemic steroids (i.e., not exceeding 10 mg/day of prednisone or an equivalent dose of other steroids) or steroids used to prevent contrast agent allergies. * steroid-dependent interstitial lung disease. * known active autoimmune disease requiring symptomatic treatment or history of such disease within the past 2 years. patients with vitiligo, psoriasis, alopecia, or -graves' disease not requiring systemic treatment within the past 2 years, hypothyroidism requiring only thyroid hormone replacement, and type i diabetes requiring only insulin replacement can be enrolled. * known history of primary immunodeficiency. * known active tuberculosis. * known history of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation. * receipt of any investigational drug treatment within the last 28 days before the study. * allergy to any drugs in the study. * pregnant or breastfeeding women. * women of childbearing potential (within 2 years of last menstruation) or men capable of fathering a child who are not using or refuse to use effective non-hormonal contraceptive methods (e.g., intrauterine device, barrier method combined with spermicide, or sterilization). * inability or unwillingness to comply with the study protocol. * presence of any other disease, functional impairment caused by metastatic lesions, or suspicious conditions found during a physical examination indicating a contraindication to the study drugs or high risk for treatment-related complications.

Keywords: metastatic colorectal cancer ras/braf wild type right-sided cetuximab pd-1 inhibitor