RAS/BRAF Wild-type Advanced Colorectal Cancer PatientsPhase 2NCT06855849
An Open-label, Single-arm, Multicenter Phase II Study to Evaluate the Efficacy of Amivantamab in Combination With FOLFIRI as a Second-line Treatment in Patients With RAS/BRAF Wild-type Advanced Colorectal Cancer Progressing on Prior Anti-EGFR Based Treatment.
A Phase 2 study testing Amivantamab + FOLFIRI in people with RAS/BRAF Wild-type Advanced Colorectal Cancer Patients, run by Yonsei University at 1 site in South Korea.
Trial summary
This trial is a multicenter, single arm study of efficacy of amivantamab in combination with FOLFIRI in RAS/BRAF wild-type advanced colorectal cancer patients progressed prior treatment including oxaliplatin based chemotherapy. Read more about this study
- Who is it for?
- Ages 19 years and older
- Conditions the study is for
- RAS/BRAF Wild-type Advanced Colorectal Cancer Patients
- What is being tested?
- Amivantamab + FOLFIRI
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 85 participants
- Where
- 1 siteSouth Korea
- Study dates
- May 2025to Dec 2027
- 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 19 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Participants must be ≥19 years of age.
- The participant must have been previously diagnosed with histologically or cytologically confirmed unresectable or metastatic adenocarcinoma of the colon or rectum.
- The participant must have a previously characterized tumor with wild-type KRAS, NRAS, and BRAF without evidence of ERBB2/HER2 amplification by immunohistochemistry (IHC) test. Local guidelines and SoC also require evaluation of dMMR/MSI-H status.
- The participant must be diagnosed with CRC and should have received anti-EGFR and oxaliplatin-based systemic therapy in the metastatic setting (no more than one prior line of systemic therapy is allowed). According to local regulatory approvals and SoC guidelines, the participant must also be eligible for treatment with FOLFIRI.
- Participants must have measurable disease according to RECIST v1.1. If only one measurable lesion exists, it may be used for the screening biopsy.
- Participants must have ECOG PS 0 or 1.
Show all 13Show fewer
- Life expectancy ≥12 weeks as judged by the Investigator.
- Participants must have adequate organ and bone marrow function as follows, without a history of red blood cell transfusion, platelet transfusion, or use of granulocyte colony-stimulating factor (G-CSF) within five days prior to the date of the laboratory test.
- Hemoglobin ≥ 8.0 g/dL B. Absolute neutrophil count ≥1.5ⅹ109/L C. Platelets ≥100ⅹ109/L D. ALT and aspartate aminotransferase (AST) ≤3ⅹupper limit of normal (ULN). If liver metastases are present, ≤ 5ⅹULN E. Total bilirubin ≤1.5ⅹULN (participants with Gilbert's syndrome can enroll if conjugated bilirubin is within normal limits) F. Serum creatinine ≤ 1.5ⅹULN, or calculated by Cockcroft-Gault formula (Refer to Appendix 9: Cockcroft-Graft Formula for Estimated Creatinine Clearance for formula) or directly measured creatinine clearance ≥ 50 mL/min
- Negative serum pregnancy test within two weeks before the first study dose in all women of childbearing potential.
- The subject and their partners must be willing to avoid pregnancy during the trial. Male subjects with female partners of childbearing potential and female subjects of childbearing potential must be willing to use adequate contraception.
- The participant must sign an ICF (or their legally acceptable representative must sign) indicating that he or she understands the purpose and procedures required for the study and is willing to participate.
- Participants must be willing and able to adhere to the lifestyle restrictions specified in this protocol.
Who cannot join
- Participants who have received prior irinotecan-based chemotherapy.
- Participants with an identified mutation in KRAS, NRAS, BRAF, or ERBB2/HER2 amplification by immunohistochemistry (IHC) test.
- Participant has an uncontrolled illness, including but not limited to the following:
- Active bleeding diathesis B. Impaired oxygenation requiring continuous oxygen supplementation C. Psychiatric illness/social situation that would limit compliance with study requirements.
- Participants have known active CNS metastases or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable, i.e., without evidence of progression for at least four weeks by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable, and without requirement of steroid treatment for at least 14 days before the first dose of study treatment.
- Participants with positive serology for HIV and HCV.
Show all 19Show fewer
- Positive hepatitis C antibody (anti-HCV [hepatitis C virus]):
- Exception: Participants with a prior history of HCV who have completed antiviral treatment and have subsequently documented HCV RNA below the lower limit of quantification per local testing are eligible.
- Anticancer treatment within 14 days before the start of trial treatment, e.g., cytoreductive therapy, radiotherapy (except for palliative bone-directed radiotherapy), immune therapy, or cytokine therapy.
- Major surgery within 28 days before the start of trial treatment (excluding prior diagnostic biopsy).
- Participants with a medical history of myocardial infarction within six months before treatment, symptomatic CHF (New York Heart Association Class II to IV), unstable angina pectoris, clinically significant cardiac arrhythmias, or a recent (< 6 months) cardiovascular event, including myocardial infarction, unstable angina pectoris, and stroke.
- Gastrointestinal perforation, fistula, or any arterial thromboembolic event within six months, or any significant gastrointestinal bleeding or significant venous thromboembolism within three months prior to treatment (except for stable venous thromboembolism on ongoing appropriate anticoagulation treatment).
- History of (non-infectious) ILD/pneumonitis, current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening.
- Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within seven days before the first dose of the study drug.
- Participants have a known previous or concurrent malignancy that has progressed or required active treatment within the past five years.
- Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (e.g., breast carcinoma or cervical cancer in situ) who have undergone potentially curative therapy are not excluded.
- Toxicities from previous anticancer therapies should have resolved to baseline levels or Grade 1 or less prior to the first dose of study treatment (except for alopecia or post-radiation skin changes [any grade], and Grade ≤2 hypothyroidism stable on hormone replacement).
- The participant has had prior chemotherapy or targeted cancer therapy with an investigational anticancer agent within two weeks or four half-lives, whichever is longer, before the first administration of the study drug.
- Any condition for which, in the opinion of the investigator, participation would not be in the best interest of the participant (e.g., compromise the well-being) or that could prevent, limit, or confound the protocol-specified assessments.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
About this study
This trial is a multicenter, single arm study of efficacy of amivantamab in combination with FOLFIRI in RAS/BRAF wild-type advanced colorectal cancer patients progressed prior treatment including oxaliplatin based chemotherapy. This trial will be conducted by Severance Hospital that is responsible for the project management of the trial. Patient recruitment will take at 3 institutions.
Participants will be treated for up to 24 cycles (approximately 2 years) after initiation of treatment with intravenous 1050mg(BW<80kg) or 1400mg(BW≥80kg) of amivantamab every 4 weeks in combination with FOLFIRI. FOLFIRI includes folic acid, 5-FU and irinotecan. FOLFIRI will be administered intravenously with folic acid 400 mg/m², 5-FU 2400 mg/m², and irinotecan 180 mg/m² every 2 weeks. This study will use ORR based on RECIST 1.1 criteria as the primary endpoint and the tumor assessment will be done every 8 weeks. Secondary endpoints are DCR, PFS, OS, and safeties. Exploratory biomarkers in tumor tissue and ctDNA in blood will be investigated in both pre-treatment and post-treatment periods.
- Being tested
- Amivantamab + FOLFIRI
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Amivantamab + FOLFIRIDrug
The dosage of amivantamab will be based on the participant's body weight during screening. Participants will receive 1,050 mg if BW is <80 kg or 1,400 mg if BW is ≥80 kg.
- Cycle 1: once weekly (with the first dose split over Day -2 [350 mg, IVF for 4-6hrs] and Day -1 [remainder of the dose, IVF for 6-8hrs]; subsequent dose [planned dose IVF over 2 hrs]).
- Cycles 2+: Days 1 and 15 of each cycle (planned dose IVF over 2 hrs) On days when both amivantamab and chemotherapy are administered, amivantamab should be administered before chemotherapy. In general, leucovorin 400 mg/m2 IV over 2 hours and irinotecan 180 mg/m2 IV over 90 min, then 5-FU 400 mg/m2 IV bolus followed by 5-FU continuous infusion 2,400 mg/m2 over approximately 46-48 hours or 1,200 mg/m2/day for two days. Irinotecan and leucovorin may be administered concurrently (via separate infusion lines) or sequentially according to the institutional standard.
| Study group | Role | What they receive |
|---|---|---|
| Amivantamab in combination with FOLFIRI | Experimental | Amivantamab will be administered as an IV infusion in 28-day cycles in combination with FOLFIRI IV infusion every 2 weeks. Receives: Drug: Amivantamab + FOLFIRI |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Response Rate
Efficacy Analysis Set includes all patients who have received at least 1 dose of the study drug, had measurable disease at baseline according to RECIST 1.1, and had at least 1 post-baseline tumor response assessment. Patients with evidence of disease progression or death before the first scheduled assessment of tumor response will be included in this Analysis Set. It will be the primary analysis set for tumor response.
Primary efficacy endpoints will be based upon investigators' tumor assessments per RECIST 1.1 and will be summarized as follows to evaluate the preliminary anticancer activities of amivantamab and FOLFIRI combination. Overall response rate (ORR) is defined as the proportion of patients who have a partial or complete response to therapy by RECIST 1.1.
Measured: every 8 weeks Up to 2 years 11 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Mar 2025
- Study startMay 2025 (estimated)
- Primary completionMay 2027 (estimated)
- Study completionDec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for RAS/BRAF Wild-type Advanced Colorectal Cancer PatientsStudies of the same condition, open and under way.
- More trials run by Yonsei 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
- 85 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Yonsei University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06855849
- Sponsor's protocol ID
- 2024-3346-002
- Status last verified
- Feb 2025
- First submitted
- 24 Feb 2025
- Last updated
- 4 Mar 2025
- Results posted
- No
- Data monitoring committee
- 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 4 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-label, Single-arm, Multicenter Phase II Study to Evaluate the Efficacy of Amivantamab in Combination With FOLFIRI as a Second-line Treatment in Patients With RAS/BRAF Wild-type Advanced Colorectal Cancer Progressing on Prior Anti-EGFR Based Treatment.
- ClinicalTrials.gov ID
- NCT06855849
- Acronym / sponsor ID
- 2024-3346-002
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 85 participants (estimated)
- Lead sponsor
- Yonsei UniversityUniversity, hospital or other
- Study start
- May 2025 (estimated)
- Primary completion
- May 2027 (estimated)
- Study completion
- Dec 2027 (estimated)
- First posted
- 4 Mar 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.
This trial is a multicenter, single arm study of efficacy of amivantamab in combination with FOLFIRI in RAS/BRAF wild-type advanced colorectal cancer patients progressed prior treatment including oxaliplatin based chemotherapy. This trial will be conducted by Severance Hospital that is responsible for the project management of the trial. Patient recruitment will take at 3 institutions.
Participants will be treated for up to 24 cycles (approximately 2 years) after initiation of treatment with intravenous 1050mg(BW<80kg) or 1400mg(BW≥80kg) of amivantamab every 4 weeks in combination with FOLFIRI. FOLFIRI includes folic acid, 5-FU and irinotecan. FOLFIRI will be administered intravenously with folic acid 400 mg/m², 5-FU 2400 mg/m², and irinotecan 180 mg/m² every 2 weeks. This study will use ORR based on RECIST 1.1 criteria as the primary endpoint and the tumor assessment will be done every 8 weeks. Secondary endpoints are DCR, PFS, OS, and safeties. Exploratory biomarkers in tumor tissue and ctDNA in blood will be investigated in both pre-treatment and post-treatment periods.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Amivantamab in combination with FOLFIRI | Experimental | Drug: Amivantamab + FOLFIRIAmivantamab will be administered as an IV infusion in 28-day cycles in combination with FOLFIRI IV infusion every 2 weeks. |
Who may qualify
- Ages
- 19 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Participants must be ≥19 years of age.
- The participant must have been previously diagnosed with histologically or cytologically confirmed unresectable or metastatic adenocarcinoma of the colon or rectum.
- The participant must have a previously characterized tumor with wild-type KRAS, NRAS, and BRAF without evidence of ERBB2/HER2 amplification by immunohistochemistry (IHC) test. Local guidelines and SoC also require evaluation of dMMR/MSI-H status.
- The participant must be diagnosed with CRC and should have received anti-EGFR and oxaliplatin-based systemic therapy in the metastatic setting (no more than one prior line of systemic therapy is allowed). According to local regulatory approvals and SoC guidelines, the participant must also be eligible for treatment with FOLFIRI.
- Participants must have measurable disease according to RECIST v1.1. If only one measurable lesion exists, it may be used for the screening biopsy.
Key exclusion criteria (19 listed)
- Participants who have received prior irinotecan-based chemotherapy.
- Participants with an identified mutation in KRAS, NRAS, BRAF, or ERBB2/HER2 amplification by immunohistochemistry (IHC) test.
- Participant has an uncontrolled illness, including but not limited to the following:
- Participants have known active CNS metastases or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable, i.e., without evidence of progression for at least four weeks by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable, and without requirement of steroid treatment for at least 14 days before the first dose of study treatment.
- Participants with positive serology for HIV and HCV.
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 |
|---|---|---|
| Amivantamab + FOLFIRIThe dosage of amivantamab will be based on the participant's body weight during screening. Participants will receive 1,050 mg if BW is <80 kg or 1,400 mg if BW is ≥80 kg. * Cycle 1: once weekly (with the first dose split over Day -2 [350 mg, IVF for 4-6hrs] and Day -1 [remainder of the dose, IVF for 6-8hrs]; subsequent dose [planned dose IVF over 2 hrs]). * Cycles 2+: Days 1 and 15 of each cycle (planned dose IVF over 2 hrs) On days when both amivantamab and chemotherapy are administered, amivantamab should be administered before chemotherapy. In general, leucovorin 400 mg/m2 IV over 2 hours and irinotecan 180 mg/m2 IV over 90 min, then 5-FU 400 mg/m2 IV bolus followed by 5-FU continuous infusion 2,400 mg/m2 over approximately 46-48 hours or 1,200 mg/m2/day for two days. Irinotecan and leucovorin may be administered concurrently (via separate infusion lines) or sequentially according to the institutional standard. | Drug | Amivantamab in combination with FOLFIRI |
Primary outcome
Overall Response Rate
Time frame: every 8 weeks Up to 2 years 11 months
Efficacy Analysis Set includes all patients who have received at least 1 dose of the study drug, had measurable disease at baseline according to RECIST 1.1, and had at least 1 post-baseline tumor response assessment. Patients with evidence of disease progression or death before the first scheduled assessment of tumor response will be included in this Analysis Set. It will be the primary analysis set for tumor response. Primary efficacy endpoints will be based upon investigators' tumor assessments per RECIST 1.1 and will be summarized as follows to evaluate the preliminary anticancer activities of amivantamab and FOLFIRI combination. Overall response rate (ORR) is defined as the proportion of patients who have a partial or complete response to therapy by RECIST 1.1.
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 4 Mar 2025.
- Individual participant dataSharing planned: No
Related trials for RAS/BRAF Wild-type Advanced Colorectal Cancer Patients
Not yet recruitingPhase 1
MTX-531-001 Phase 1 Study in Advanced Solid Tumors
Solid Tumors (Phase 1), HNSCC
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.
The record lists no contact. Use the official record to reach the sponsor.
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 Amivantamab + FOLFIRI in people with RAS/BRAF Wild-type Advanced Colorectal Cancer Patients, run by Yonsei University at 1 site in South Korea.
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 13 inclusion and 19 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 4 Mar 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 South Korea. 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?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall Response Rate (time frame: every 8 weeks Up to 2 years 11 months). 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 4 Mar 2025; AzTrials last refreshed its copy on 28 Oct 2026.