Combining cetuximab, irinotecan, and a PD-1 inhibitor for treating specific colorectal cancer

Negative Ultraselection of Patients With RAS/BRAF Wild-type Refractory Right-Sided Metastatic Colorectal Cancer Receiving Cetuximab in Combination With Toripalimab and Irinotecan: A Phase II, Single-arm Study

This study is testing a new combination of treatments for patients with hard-to-treat right-sided colorectal cancer to see if it can help them when other options haven't worked.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 34 (estimated)
• Ages: 18 Years to 80 Years
• Sex: All
• Sponsor: Sun Yat-sen University (Academic / other)
• Drugs / interventions: bevacizumab, prednisone, cetuximab
• Locations: 1 site (Guangzhou, Guangdong)
• Trial ID: NCT06547203 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the efficacy and safety of a combination therapy involving cetuximab, a PD-1 inhibitor, and irinotecan for patients with refractory right-sided metastatic colorectal cancer that is RAS/BRAF wild-type. The study specifically targets patients who have not responded to previous treatments and have undergone ultraselection for specific genetic mutations. By focusing on this unique patient population, the trial aims to provide new insights into treatment options for a group that typically has poorer outcomes. The methodology includes assessing the response to treatment based on measurable lesions and overall patient health.

Who should consider this trial

Good fit: Ideal candidates for this study are patients with histologically confirmed right-sided colorectal adenocarcinoma who are RAS/BRAF wild-type and have progressed after standard treatments.

Not a fit: Patients with left-sided colorectal cancer or those who have previously received anti-EGFR or PD-1 therapies may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could provide a new effective treatment option for patients with refractory right-sided metastatic colorectal cancer.

How similar studies have performed: While there is limited clinical data on the use of EGFR inhibitors for right-sided metastatic colorectal cancer, retrospective analyses suggest varying efficacy outcomes, indicating that this approach is novel and underexplored.

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.

Where this trial is running

Guangzhou, Guangdong

• Sun Yat-sen University Cancer Center — Guangzhou, Guangdong, China (Recruiting)

Study contacts

• Study coordinator: Yuhong Li, PhD

Conditions Colorectal Cancer Metastatic; Metastatic colorectal cancer; RAS/BRAF wild type; Right-sided; Cetuximab; PD-1 inhibitor