Dual EGFR/HER2 Blockade Combined With Irinotecan for the Treatment of HER2-Positive Metastatic Colorectal Cancer

Launched by SUN YAT-SEN UNIVERSITY · Jul 7, 2025

Keywords

ClinConnect Summary

This clinical trial is studying a new treatment approach for people with advanced colorectal cancer that tests positive for a protein called HER2. This type of cancer has spread to other parts of the body and has not responded well to standard chemotherapy treatments. The goal is to see if combining two targeted medicines—trastuzumab and cetuximab beta, which work by blocking HER2 and another protein called EGFR—along with a chemotherapy drug called irinotecan, can better control the cancer and slow its growth.

To be eligible, participants need to be between 18 and 75 years old with HER2-positive colorectal cancer that has spread, and their tumor must not have certain gene mutations (KRAS, NRAS, or BRAF). They should have already tried standard chemotherapy but had their cancer continue to grow. Participants will need to be in good overall health and able to follow the study’s schedule. If someone joins, they can expect to receive the combination treatment and be closely monitored for how the cancer responds and for any side effects. This study is not yet open for enrollment, but it offers hope for people whose cancer is resistant to current treatments by targeting two important proteins at the same time.

Gender

ALL

Eligibility criteria

• Inclusion Criteria:
• • Signed and dated informed consent must be obtained voluntarily from the subject prior to performing any study-related procedures (non-routine care), in accordance with regulatory and institutional guidelines.
• • 18 to 75 years of age, inclusive.
• • Histologically or cytologically confirmed adenocarcinoma of the colon or rectum with evidence of distant metastasis.
• • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• • HER2-positive tumor with wild-type KRAS, NRAS, and BRAF genes confirmed by testing at any time prior to screening. HER2 positivity is defined as: Immunohistochemistry (IHC) showing HER2 3+ staining in \>50% of tumor cells; or HER2 2+ by IHC with positive fluorescence in situ hybridization (FISH): HER2/CEP17 ratio ≥2.0 in \>50% of tumor cells; or Next-generation sequencing (NGS) of tissue or circulating tumor DNA (ctDNA) demonstrating HER2 copy number ≥6.
• * Adequate organ function as evidenced by:
• • Absolute neutrophil count ≥1.5×10\^9/L Platelet count ≥75×10\^9/L Serum total bilirubin ≤1.5×upper normal limit (UNL) Aspartate aminotransferase (AST) ≤2.5×UNL Alanine aminotransferase (ALT) ≤2.5×UNL Serum creatinine ≤1.5×UNL
• • Disease progression after prior treatment with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy, including: Subjects who received oxaliplatin in the adjuvant setting must have experienced disease progression within 6 months after completing adjuvant therapy.Patients who decline standard therapy due to intolerable toxicity are eligible.
• • Presence of at least one measurable lesion per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
• • Willing and able to comply with the study protocol and visit schedule
• Exclusion Criteria:
• • Known KRAS, NRAS, or BRAF mutations detected by ctDNA testing prior to enrollment; or tumors with mismatch repair deficiency (dMMR) or high microsatellite instability (MSI-H).
• • Concurrent intestinal obstruction, active bleeding, or perforation requiring emergency surgery.
• • Major surgery (e.g., laparotomy, thoracotomy, or organ resection via laparoscopy) or significant trauma within 4 weeks prior to study entry (surgical incision must be fully healed before enrollment).
• • Active coronary artery disease within 12 months before screening, including severe/unstable angina, newly diagnosed angina, or myocardial infarction.
• • History of thrombosis or embolism within 6 months, including cerebrovascular accident (transient ischemic attack included), pulmonary embolism, or deep vein thrombosis.
• • Congestive heart failure classified as New York Heart Association (NYHA) Class II or higher.
• • HIV infection or AIDS; untreated active hepatitis (HBV-DNA ≥500 IU/mL for hepatitis B; detectable HCV-RNA for hepatitis C); or HBV/HCV co-infection.
• • Interstitial lung disease, non-infectious pneumonitis, or uncontrolled systemic diseases (e.g., diabetes, hypertension, pulmonary fibrosis, acute pneumonia).
• • Persistent ≥Grade 2 toxicities (per CTCAE v5.0) from prior therapies (excluding peripheral neuropathy, anemia, alopecia, or skin hyperpigmentation).
• • Known or suspected hypersensitivity to any study drugs.
• • Pregnancy or lactation.