BRAF V600E-mutated /MSS Metastatic Colorectal CancerPhase 1NCT05019534
Tolerability and Safety of Vemurafenib, Cetuximab Combined With Camrelizumab for BRAF V600E-mutated /MSS Metastatic Colorectal Cancer
A Phase 1 study testing Vemurafenib Oral Tablet [Zelboraf], Cetuximab Injection [Erbitux] and Camrelizumab in people with BRAF V600E-mutated /MSS Metastatic Colorectal Cancer and Vemurafenib (BRAFi) Plus Cetuximab (EGFRi) Combined With PD-1 Monoclonal Antibody, run by West China Hospital at 1 site in China.
Trial summary
BRAF mutation exists in about 10-12% of colorectal cancer, among which BRAF V600E mutation is the most common type, which is an important biomarker for predicting the prognosis and precise treatment efficacy of metastatic colorectal cancer (mCRC). Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- BRAF V600E-mutated /MSS Metastatic Colorectal Cancer, Vemurafenib (BRAFi) Plus Cetuximab (EGFRi) Combined With PD-1 Monoclonal Antibody
- What is being tested?
- Vemurafenib Oral Tablet [Zelboraf], Cetuximab Injection [Erbitux] and Camrelizumab
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 1 siteChina
- Study dates
- 15 Aug 2021to 1 Dec 2022
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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
- Male or female ≥ 18 years of age
- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2
- Participants must have histologically or cytologically confirmed diagnosis of adenocarcinoma of the colon or rectum, with clinical confirmation of unresectable and/or metastatic disease that is measurable according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1) criteria
- Presence of BRAF V600E in tumor tissue determined by local assay at any time prior to screening and confirmed by central laboratory. And confirmation of MSS or pMMR status from immunohistochemistry or PCR or NGS;
- Prior treatment with at least one systemic treatment (chemotherapy or target therapy) for mCRC, and prior treatment did not include cetuximab
- Adequate organ and marrow function:
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- ①Hemoglobin (Hb) ≥ 90 g/L；Platelets (PLT) ≥ 75 x 10^9/L；Neutrophil ≥1.5 x 10^9/L
- ②Total bilirubin ≤ 1.5 x upper limit of normal (ULN)；Aspartate aminotransferase (AST) ≤3 x ULN ；Alanine aminotransferase (ALT) ≤3 x ULN
- ③Serum creatinine ≤ 1.5 x ULN, or calculated creatinine clearance (determined as per Cockcroft-Gault) ≥ 50 mL/min at screening
- ④INR, APTT, and PT≤ 1.5 x ULN
- ⑤Serum albumin≥ 28 g/L
- ⑥ECG showed no evident abnormality
- Written informed consent
Who cannot join
- Known hypersensitivity or contraindication to any component of cetuximab or PD-1 monoclonal antibody or macromolecular protein reagent.
- A history of other malignancies with a disease-free survival of less than 5 years, with the following exceptions: adequately treated basal or squamous cell skin cancer, carcinoma in-situ of the cervix, and gastrointestinal tumors treated curatively with endoscopic mucosectomy;
- Any active autoimmune disease or a history of autoimmune disease
- Use of immunosuppressive medications or glucocorticoid therapy ≤2 weeks prior to entry
- Uncontrolled active infection requiring antibiotics
- Known history of HIV infection or active hepatitis
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- Severe complications, including any of the following:
- ①Massive gastrointestinal bleeding, perforation, or gastrointestinal obstruction
- ②Symptomatic heart disease
- ③Uncontrolled diabetes and hypertension
- ④Uncontrolled diarrhea
- Women who are pregnant or lactating and people who do not agree to avoid pregnancy
- Patients with serious psychiatric that may interfere treatment.
- Other conditions which are inappropriate to participate in the study confirmed by investigators.
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Sichuan University West China Hospital
Chengdu, Sichuan, 610044
Weibing Leng, Ph.D, +8618980601776, s103470@stu.scu.edu.cn
About this study
Official title: A Phase I Study on Tolerance and Safety of Vemurafenib Film-coated Tablets, Cetuximab Solution for Infusion and Camrelizumab Protocol(VCC) in the After Line Therapy of BRAF V600E Mutation/MSS Metastatic Colorectal Cancer
BRAF mutation exists in about 10-12% of colorectal cancer, among which BRAF V600E mutation is the most common type, which is an important biomarker for predicting the prognosis and precise treatment efficacy of metastatic colorectal cancer (mCRC). The prognosis of metastatic colorectal cancer with BRAF V600E mutation is very poor, with OS of about 6-9 months. Previous studies have shown that single anti-BRAF inhibitor are ineffective, while multi-target inhibitions of Ras-Raf -MEK pathway is a possible effective strategy for BRAF V600E-mutant mCRC. Currently, the proven effective regimens include the VIC regimen (Vemurafenib + cetuximab + Irinotecan) and BEACON regimen (Encorafenib+ cetuximab +/- Binimetinib) from the SWOGS1406 study. Furthermore, BRAF inhibitor +MEK inhibitor combined with PD-1 monoclonal antibody has been shown to be an effective strategy in BRAF V600E-mutant malignant melanoma, which promote the study of the regimens for the treatment of BRAF V600E-mutant mCRC. Increasing basic and clinical studies have shown that cetuximab has ADCC effect, induces immunogenic cell death, promotes immune cell infiltration and other immunomodulatory effects, and has a synergistic effect with PD-1 monoclonal antibody in colorectal cancer. Based on those theories, we conducted the phase I study to explore the safety and preliminary efficacy of the regimen of Vemurafenib (BRAFi) plus cetuximab (EGFRi) combined with PD-1 monoclonal antibody in BRAF V600E-mutant /MSS type mCRC.
- Conditions
- BRAF V600E-mutated /MSS Metastatic Colorectal Cancer, Vemurafenib (BRAFi) Plus Cetuximab (EGFRi) Combined With PD-1 Monoclonal Antibody
- Being tested
- Vemurafenib Oral Tablet [Zelboraf], Cetuximab Injection [Erbitux], Camrelizumab
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Vemurafenib Oral Tablet [Zelboraf]Drug
Also called Zelboraf
Vemurafenib 960mg qd or 960mg bid (2 cohorts)
Cetuximab Injection [Erbitux]Drug
Also called Erbitux
Cetuximab 500mg/m2 Q2W
CamrelizumabDrug
Camrelizumab 200mg Q2W
| Study group | Role | What they receive |
|---|---|---|
| Vemurafenib, Cetuximab Combined With Camrelizumab (VCC) | Experimental | Cetuximab and Camrelizumab in the fixed dose Vemurafenib have two dose groups: 960mg qd or 960mg bid Receives: Drug: Vemurafenib Oral Tablet [Zelboraf]; Drug: Cetuximab Injection [Erbitux]; Drug: Camrelizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Evaluate tolerability and safety and identify the recommended Phase 2 dose(RP2D)
Measured: Subjects will be treated and observed for dose-limiting toxicity(DLT) through the end of the first cycle (Days 1-28)
Secondary outcomes (5)
Object Response Rate (ORR)
Rate of patients with partial or complete response according to modified RECIST criteria.
Measured: up to 24 weeks
Disease Control Rate (DCR)
the proportion of patients who had a best response rating of complete response, partial response, or stable disease according to modified RECIST
Measured: up to 24 weeks
Progression Free Survival (PFS)
Progression free survival (Medium, Kaplan-Meier-estimation, ITT- population)
Measured: up to 1 year
Overall Survival (OS)
Overall survival (Kaplan-Meier-estimation, ITT- population)
Measured: up to 3 year
Preliminary efficacy
Evaluation of preliminary efficacyaccording to RECIST 1.1
Measured: up to 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Aug 2021
- Study start15 Aug 2021
- Primary completion1 Aug 2022 (estimated)
- Study completion1 Dec 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for BRAF V600E-mutated /MSS Metastatic Colorectal CancerStudies of the same condition, open and under way.
- More trials run by West China HospitalThe 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 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 12 participants (estimated)
Sponsor and investigators
- Lead sponsor
- West China Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Meng Qiu, West China Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05019534
- Sponsor's protocol ID
- ChiECRCT20210210
- Status last verified
- May 2022
- First submitted
- 5 Aug 2021
- Last updated
- 19 May 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Wei GX, Zhou YW, Cao P, Leng WB, Wang L, Tang J, Qiu M. Vemurafenib, cetuximab and camrelizumab in BRAF V600E-mutated/MSS metastatic colorectal cancer. J Transl Med. 2025 Nov 12;23(1):1274. doi: 10.1186/s12967-025-07312-6.
PubMed 41225509
Study at a glance
From the registry record, last updated by the sponsor on 19 May 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Study on Tolerance and Safety of Vemurafenib Film-coated Tablets, Cetuximab Solution for Infusion and Camrelizumab Protocol(VCC) in the After Line Therapy of BRAF V600E Mutation/MSS Metastatic Colorectal Cancer
- ClinicalTrials.gov ID
- NCT05019534
- Acronym / sponsor ID
- ChiECRCT20210210
- Conditions
- BRAF V600E-mutated /MSS Metastatic Colorectal Cancer, Vemurafenib (BRAFi) Plus Cetuximab (EGFRi) Combined With PD-1 Monoclonal Antibody
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 12 participants (estimated)
- Lead sponsor
- West China HospitalUniversity, hospital or other
- Study start
- 15 Aug 2021 (actual)
- Primary completion
- 1 Aug 2022 (estimated)
- Study completion
- 1 Dec 2022 (estimated)
- First posted
- 25 Aug 2021 (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.
BRAF mutation exists in about 10-12% of colorectal cancer, among which BRAF V600E mutation is the most common type, which is an important biomarker for predicting the prognosis and precise treatment efficacy of metastatic colorectal cancer (mCRC). The prognosis of metastatic colorectal cancer with BRAF V600E mutation is very poor, with OS of about 6-9 months. Previous studies have shown that single anti-BRAF inhibitor are ineffective, while multi-target inhibitions of Ras-Raf -MEK pathway is a possible effective strategy for BRAF V600E-mutant mCRC. Currently, the proven effective regimens include the VIC regimen (Vemurafenib + cetuximab + Irinotecan) and BEACON regimen (Encorafenib+ cetuximab +/- Binimetinib) from the SWOGS1406 study. Furthermore, BRAF inhibitor +MEK inhibitor combined with PD-1 monoclonal antibody has been shown to be an effective strategy in BRAF V600E-mutant malignant melanoma, which promote the study of the regimens for the treatment of BRAF V600E-mutant mCRC. Increasing basic and clinical studies have shown that cetuximab has ADCC effect, induces immunogenic cell death, promotes immune cell infiltration and other immunomodulatory effects, and has a synergistic effect with PD-1 monoclonal antibody in colorectal cancer. Based on those theories, we conducted the phase I study to explore the safety and preliminary efficacy of the regimen of Vemurafenib (BRAFi) plus cetuximab (EGFRi) combined with PD-1 monoclonal antibody in BRAF V600E-mutant /MSS type mCRC.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Vemurafenib, Cetuximab Combined With Camrelizumab (VCC) | Experimental | Drug: Vemurafenib Oral Tablet [Zelboraf], Drug: Cetuximab Injection [Erbitux], Drug: CamrelizumabCetuximab and Camrelizumab in the fixed dose Vemurafenib have two dose groups: 960mg qd or 960mg bid |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Male or female ≥ 18 years of age
- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2
- Participants must have histologically or cytologically confirmed diagnosis of adenocarcinoma of the colon or rectum, with clinical confirmation of unresectable and/or metastatic disease that is measurable according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1) criteria
- Presence of BRAF V600E in tumor tissue determined by local assay at any time prior to screening and confirmed by central laboratory. And confirmation of MSS or pMMR status from immunohistochemistry or PCR or NGS;
- Prior treatment with at least one systemic treatment (chemotherapy or target therapy) for mCRC, and prior treatment did not include cetuximab
Key exclusion criteria (14 listed)
- Known hypersensitivity or contraindication to any component of cetuximab or PD-1 monoclonal antibody or macromolecular protein reagent.
- A history of other malignancies with a disease-free survival of less than 5 years, with the following exceptions: adequately treated basal or squamous cell skin cancer, carcinoma in-situ of the cervix, and gastrointestinal tumors treated curatively with endoscopic mucosectomy;
- Any active autoimmune disease or a history of autoimmune disease
- Use of immunosuppressive medications or glucocorticoid therapy ≤2 weeks prior to entry
- Uncontrolled active infection requiring antibiotics
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 |
|---|---|---|
| Vemurafenib Oral Tablet [Zelboraf]Also: ZelborafVemurafenib 960mg qd or 960mg bid (2 cohorts) | Drug | Vemurafenib, Cetuximab Combined With Camrelizumab (VCC) |
| Cetuximab Injection [Erbitux]Also: ErbituxCetuximab 500mg/m2 Q2W | Drug | Vemurafenib, Cetuximab Combined With Camrelizumab (VCC) |
| CamrelizumabCamrelizumab 200mg Q2W | Drug | Vemurafenib, Cetuximab Combined With Camrelizumab (VCC) |
Primary outcome
Evaluate tolerability and safety and identify the recommended Phase 2 dose(RP2D)
Time frame: Subjects will be treated and observed for dose-limiting toxicity(DLT) through the end of the first cycle (Days 1-28)
5 secondary outcomes
Object Response Rate (ORR)
Time frame: up to 24 weeks
Disease Control Rate (DCR)
Time frame: up to 24 weeks
Progression Free Survival (PFS)
Time frame: up to 1 year
Overall Survival (OS)
Time frame: up to 3 year
Preliminary efficacy
Time frame: up to 1 year
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 May 2022.
- Derived from this study: PubMed 41225509Wei GX, Zhou YW, Cao P, Leng WB, Wang L, Tang J, Qiu M. Vemurafenib, cetuximab and camrelizumab in BRAF V600E-mutated/MSS metastatic colorectal cancer. J Transl Med. 2025 Nov 12;23(1):1274. doi: 10.1186/s12967-025-07312-6.
- 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. This study is not recruiting at the moment.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Vemurafenib Oral Tablet [Zelboraf], Cetuximab Injection [Erbitux] and Camrelizumab in people with BRAF V600E-mutated /MSS Metastatic Colorectal Cancer and Vemurafenib (BRAFi) Plus Cetuximab (EGFRi) Combined With PD-1 Monoclonal Antibody, run by West China Hospital 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 13 inclusion and 14 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: status not confirmed, as of the sponsor's last update on 19 May 2022. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Meng Qiu (+862885423203, qiumeng33@hotmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Evaluate tolerability and safety and identify the recommended Phase 2 dose(RP2D) (time frame: Subjects will be treated and observed for dose-limiting toxicity(DLT) through the end of the first cycle (Days 1-28)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05019534, which also lists 1 linked publication.
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 19 May 2022.