HER2 PositivePhase 2HERBICNCT07059338
Dual EGFR/HER2 Blockade Combined With Irinotecan for the Treatment of HER2-Positive Metastatic Colorectal Cancer
A Phase 2 study testing Trastuzumab +Cetuximab β+Irinotecan in people with HER2 Positive and Colorectal Cancer (CRC), run by Sun Yat-sen University at 1 site in China.
Trial summary
In colorectal cancer (CRC), HER2 has emerged as a critically targeted biomarker in recent years. Although multiple clinical trials have demonstrated the potential of HER2-targeted therapies in HER2-positive (overexpressed/amplified) metastatic CRC (mCRC), the duration of treatment response remains short with rapid… Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- HER2 Positive, Colorectal Cancer (CRC)
- What is being tested?
- Trastuzumab +Cetuximab β+Irinotecan
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 34 participants
- Where
- 1 siteChina
- Study dates
- 11 Jul 2025to 30 Dec 2028
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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:
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- 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
Who cannot join
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site
The Sixth Affiliated Hospital of Sun Yat-sen University
Guangzhou
Yanhong Deng, 86+13925106525, dengyanh@mail.sysu.edu.cn
About this study
Official title: Trastuzumab in Combination With Cetuximab and Irinotecan for the Treatment of HER2-Positive Metastatic Colorectal Cancer：A Phase II, Open-Label Trial
In colorectal cancer (CRC), HER2 has emerged as a critically targeted biomarker in recent years. Although multiple clinical trials have demonstrated the potential of HER2-targeted therapies in HER2-positive (overexpressed/amplified) metastatic CRC (mCRC), the duration of treatment response remains short with rapid disease progression. This underscores the urgent need to develop novel therapeutic strategies for HER2-positive mCRC. The EGFR pathway is constitutively activated in CRC and mediates resistance to HER2-targeted therapies through the formation of EGFR-HER2 heterodimers. Notably, EGFR-targeting antibodies combined with irinotecan can reverse irinotecan chemoresistance. Building upon these mechanisms, this study proposes to evaluate the combination of trastuzumab (anti-HER2), cetuximab beta (anti-EGFR), and irinotecan in chemotherapy-refractory HER2-positive mCRC.
Read the detailed description
In colorectal cancer (CRC), HER2 has emerged as a significant therapeutic target, with clinical studies demonstrating promising yet transient responses to HER2-targeted therapies in HER2-positive (overexpressed/amplified) advanced cases, highlighting the need for improved strategies. Mechanistically, in the 65-75% of CRCs exhibiting EGFR overexpression, HER2 promotes heterodimerization with EGFR, impairing internalization of HER2-targeted ADCs and reducing drug uptake. Preclinical evidence suggests EGFR monoclonal antibodies (cetuximab/panitumumab) may overcome this limitation by inducing EGFR internalization and enhancing HER2-targeted drug efficacy. However, HER2-positive advanced CRC lacks validated predictive biomarkers and thorough translational research. Our study will clinically evaluate trastuzumab plus cetuximab and irinotecan in this population, while performing longitudinal biomarker analyses of paired blood and tumor samples to identify response predictors, elucidate resistance mechanisms, and optimize this promising therapeutic approach.
- Conditions
- HER2 Positive, Colorectal Cancer (CRC)
- Being tested
- Trastuzumab +Cetuximab β+Irinotecan
- Keywords
- colorectal cancer
- Medical subject headings
- Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Trastuzumab +Cetuximab β+IrinotecanDrug
Also called HER2 and EGFR dual-targeted therapy combined with irinotecan
Trastuzumab 4 mg/kg , Cetuximab β: 500 mg/m² ,Irinotecan 180 mg/m², repeat once every 2 weeks
| Study group | Role | What they receive |
|---|---|---|
| Trastuzumab +Cetuximab β+Irinotecan | Experimental | Treatment regimen: All agents will be administered via intravenous infusion, consisting of trastuzumab (4 mg/kg every 2 weeks), cetuximab beta (500 mg/m² every 2 weeks) in combination with irinotecan (180 mg/m² every 2 weeks). Comprehensive radiological and laboratory assessments will be conducted after every 4 treatment cycles (8 weeks). Receives: Drug: Trastuzumab +Cetuximab β+Irinotecan |
What is being measured
The primary outcome is the main question the study is designed to answer.
6-month progression-free-survival rates
Progression-free survival defined as the time from randomization to documented disease progression according to RECIST or death from any cause. We computed the 6-month PFS rate based on the available follow-up data.
Measured: 2 years
Secondary outcomes (4)
Objective response rate
defined as the percentage of patients with complete or partial response according to RECIST
Measured: 2 years
Disease control rate
defined as the percentage of patients with CR + PR + SD according to RECIST
Measured: 2 years
overall survival
defined as the time from randomization to death from any cause
Measured: 3 years
Incidence of participants with treatment-related adverse events as assessed by CTCAE v5.0
Percentage of patients, experiencing a specific adverse event, according to National Cancer Institute Common Toxicity Criteria (version 5.0), during the induction and the maintenance phases of treatment.
Measured: 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Jul 2025
- Study start11 Jul 2025 (estimated)
- Primary completion30 Dec 2027 (estimated)
- Study completion30 Dec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HER2 PositiveStudies of the same condition, open and under way.
- More trials run by Sun Yat-sen UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 34 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Sun Yat-sen University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Yanhong Deng, Sun Yat-sen University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07059338
- Sponsor's protocol ID
- 2025ZSLYEC-160
- Acronym
- HERBIC
- Status last verified
- Jul 2025
- First submitted
- 5 Jun 2025
- Last updated
- 10 Jul 2025
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 Jul 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Trastuzumab in Combination With Cetuximab and Irinotecan for the Treatment of HER2-Positive Metastatic Colorectal Cancer：A Phase II, Open-Label Trial
- ClinicalTrials.gov ID
- NCT07059338
- Acronym / sponsor ID
- HERBIC / 2025ZSLYEC-160
- Conditions
- HER2 Positive, Colorectal Cancer (CRC)
- Keywords
- colorectal cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 34 participants (estimated)
- Lead sponsor
- Sun Yat-sen UniversityUniversity, hospital or other
- Study start
- 11 Jul 2025 (estimated)
- Primary completion
- 30 Dec 2027 (estimated)
- Study completion
- 30 Dec 2028 (estimated)
- First posted
- 10 Jul 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
In colorectal cancer (CRC), HER2 has emerged as a critically targeted biomarker in recent years. Although multiple clinical trials have demonstrated the potential of HER2-targeted therapies in HER2-positive (overexpressed/amplified) metastatic CRC (mCRC), the duration of treatment response remains short with rapid disease progression. This underscores the urgent need to develop novel therapeutic strategies for HER2-positive mCRC. The EGFR pathway is constitutively activated in CRC and mediates resistance to HER2-targeted therapies through the formation of EGFR-HER2 heterodimers. Notably, EGFR-targeting antibodies combined with irinotecan can reverse irinotecan chemoresistance. Building upon these mechanisms, this study proposes to evaluate the combination of trastuzumab (anti-HER2), cetuximab beta (anti-EGFR), and irinotecan in chemotherapy-refractory HER2-positive mCRC.
Detailed description
In colorectal cancer (CRC), HER2 has emerged as a significant therapeutic target, with clinical studies demonstrating promising yet transient responses to HER2-targeted therapies in HER2-positive (overexpressed/amplified) advanced cases, highlighting the need for improved strategies. Mechanistically, in the 65-75% of CRCs exhibiting EGFR overexpression, HER2 promotes heterodimerization with EGFR, impairing internalization of HER2-targeted ADCs and reducing drug uptake. Preclinical evidence suggests EGFR monoclonal antibodies (cetuximab/panitumumab) may overcome this limitation by inducing EGFR internalization and enhancing HER2-targeted drug efficacy. However, HER2-positive advanced CRC lacks validated predictive biomarkers and thorough translational research. Our study will clinically evaluate trastuzumab plus cetuximab and irinotecan in this population, while performing longitudinal biomarker analyses of paired blood and tumor samples to identify response predictors, elucidate resistance mechanisms, and optimize this promising therapeutic approach.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Trastuzumab +Cetuximab β+Irinotecan | Experimental | Drug: Trastuzumab +Cetuximab β+IrinotecanTreatment regimen: All agents will be administered via intravenous infusion, consisting of trastuzumab (4 mg/kg every 2 weeks), cetuximab beta (500 mg/m² every 2 weeks) in combination with irinotecan (180 mg/m² every 2 weeks). Comprehensive radiological and laboratory assessments will be conducted after every 4 treatment cycles (8 weeks). |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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.
Key exclusion criteria (11 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Trastuzumab +Cetuximab β+IrinotecanAlso: HER2 and EGFR dual-targeted therapy combined with irinotecanTrastuzumab 4 mg/kg , Cetuximab β: 500 mg/m² ,Irinotecan 180 mg/m², repeat once every 2 weeks | Drug | Trastuzumab +Cetuximab β+Irinotecan |
Primary outcome
6-month progression-free-survival rates
Time frame: 2 years
Progression-free survival defined as the time from randomization to documented disease progression according to RECIST or death from any cause. We computed the 6-month PFS rate based on the available follow-up data.
4 secondary outcomes
Objective response rate
Time frame: 2 years
Disease control rate
Time frame: 2 years
overall survival
Time frame: 3 years
Incidence of participants with treatment-related adverse events as assessed by CTCAE v5.0
Time frame: 3 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Jul 2025.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Trastuzumab +Cetuximab β+Irinotecan in people with HER2 Positive and Colorectal Cancer (CRC), run by Sun Yat-sen University at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 10 Jul 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Yanhong Deng (86-13925106525, 13925106525@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
6-month progression-free-survival rates (time frame: 2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Jul 2025.