Colorectal CancerPhase 2NCT07809893
Ivosidenib Plus mFOLFOXIRI and Celecoxib for BRAF-targeted Therapy-refractory BRAF V600E-mutant Colorectal Cancer Patients
A Phase 2 study testing Ivonescimab +mFOLFOXIRI +celecoxib in people with Colorectal Cancer, run by Sun Yat-sen University at 1 site in China.
Trial summary
BRAF-mutated colorectal cancer, primarily driven by the BRAF V600E mutation, accounts for approximately 5-10% of all colorectal cancer cases and is associated with aggressive disease progression and poor prognosis, particularly in metastatic settings. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Colorectal Cancer
- What is being tested?
- Ivonescimab +mFOLFOXIRI +celecoxib
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 45 participants
- Where
- 1 siteChina
- Study dates
- 10 Aug 2026to 30 Jun 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 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Signed the informed consent form voluntarily.
- Aged 18-70.
- Colorectal adenocarcinoma with definite histological evidence, with evidence of distant metastasis;
- Diagnosed with colon or rectal adenocarcinoma, with evidence of distant metastasis;
- Genetic testing indicates a BRAF V600E mutation;
- Previously received first-line treatment including FOLFOX/CAPOX or FOLFIRI/CAPIRI and experienced disease progression or intolerance. Among them, patients who used oxaliplatin in adjuvant therapy should have experienced disease progression within 12 months after completing adjuvant therapy; Previously received anti-BRAF V600E targeted therapy and failed, including but not limited to vemurafenib, dabrafenib, and encorafenib;
Show all 11Show fewer
- Patients must have measurable lesions according to the Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1.
- Adequate organ function based on the following laboratory test values obtained within 7 days prior to treatment: neutrophil count ≥1.5×109/L, platelet count ≥75×109/L, serum total bilirubin ≤1.5× upper limit of normal value (UNL), aspartate transferase ≤2.5×UNL, alanine transferase ≤2.5×UNL, serum creatinine ≤2.5×UNL;
- Female subjects must be either postmenopausal for at least 1 year, have undergone surgical sterilization at least 6 weeks prior, or must agree to use appropriate contraceptive measures;
- Male subjects must agree to use appropriate contraceptive measures to prevent their partners from becoming pregnant;
- Willing and able to comply with research protocols and visit plans.
Who cannot join
- Prior to enrollment, ctDNA testing shows known KRAS mutation, NRAS mutation, or ERBB2 gene amplification; tumor tissue testing shows mismatch repair gene deficiency or high microsatellite instability, KRAS mutation, NRAS mutation, or ERBB2 gene amplification;
- Presence of intestinal obstruction, active bleeding, or intestinal perforation requiring emergency intervention;
- Underwent major surgery or severe trauma in the previous 4 weeks;
- Active coronary artery disease, severe/unstable angina, or newly diagnosed angina or myocardial infarction within 12 months prior to study participation;
- Occurrence of thrombotic or embolic events within the past 6 months;
- New York Heart Association (NYHA) class II or higher congestive heart failure;
Show all 13Show fewer
- Human immunodeficiency virus (HIV) infection or known acquired immunodeficiency syndrome (AIDS), untreated active hepatitis;
- Any active, known, or suspected autoimmune disease.
- Presence of interstitial lung disease, non-infectious pneumonia, or uncontrolled systemic disease;
- Any unresolved treatment-related adverse events of grade 2 or higher according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 (excluding peripheral neuropathy, anemia, hair loss, and skin pigmentation);
- Previous treatment with programmed cell death protein-1 (PD-1) and its ligand (PD-L1) inhibitors or anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) antibodies;
- Known or suspected history of allergy to any of the related drugs used in the study;
- Pregnant or breastfeeding women.
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, 1 recruiting
- Recruiting
Gastrointestinal Hospital, Sun Yat-sen University
Guangzhou, Guangdong, 510655
Yanhong Deng, 00862013925106525, dengyanh@mail.sysu.edu.cn
About this study
Official title: Ivosidenib Plus mFOLFOXIRI and Celecoxib as a Treatment for BRAF-targeted Therapy-refractory BRAF V600E-mutant Colorectal Cancer Patients: a Phase II Study
BRAF-mutated colorectal cancer, primarily driven by the BRAF V600E mutation, accounts for approximately 5-10% of all colorectal cancer cases and is associated with aggressive disease progression and poor prognosis, particularly in metastatic settings. Following first- and second-line treatments, including chemotherapy and targeted therapy, the median overall survival of patients is typically less than 24 months, and tumor progression is rapid once resistance develops. Previous studies have demonstrated that immune checkpoint inhibitors, such as anti-PD-1 therapies, show limited efficacy in microsatellite-stable (MSS) colorectal cancers but may hold promise when combined with other agents to overcome resistance mechanisms. Ivonescimab, a bispecific antibody targeting PD-1 and VEGF, has shown antitumor activity in various solid tumors by simultaneously inhibiting immune evasion and angiogenesis. The combination of ivonescimab with intensive chemotherapy like FOLFOXIRI (folinic acid, 5-fluorouracil, oxaliplatin, and irinotecan) and the COX-2 inhibitor celecoxib aims to enhance antitumor immunity, reduce inflammation, and improve vascular normalization in resistant tumors. However, there are no reported studies on this specific combination for chemotherapy- and BRAF inhibitor-resistant BRAF-mutated colorectal cancer. Therefore, the aim of this study is to evaluate the efficacy and safety of ivonescimab combined with FOLFOXIRI and celecoxib in patients with chemotherapy- and BRAF inhibitor-resistant BRAF-mutated advanced colorectal cancer, with a focus on assessing objective response rate (ORR) and tolerability.
Read the detailed description
This study is a prospective, investigator-initiated, single-arm, phase II trial to evaluate the efficacy and safety of ivonescimab (AK112) combined with FOLFOXIRI and celecoxib in patients with BRAF-mutated advanced/metastatic colorectal cancer who have developed resistance to prior chemotherapy and BRAF inhibitors . The inclusion criteria: histologically confirmed BRAF V600E-mutated advanced or metastatic colorectal cancer; documented resistance/progression after at least one line of standard chemotherapy ( FOLFOX/FOLFIRI-based) and BRAF inhibitor-based targeted therapy; measurable disease per RECIST 1.1; ECOG performance status 0-1; adequate organ function; no active brain metastases or other uncontrolled comorbidities (specific criteria can be supplemented as needed). Patients received ivonescimab combined with mFOLFOXIRI (modified FOLFOXIRI regimen) and celecoxib for up to 6-8 cycles or until progression/toxicity, followed by maintenance therapy of continued ivonescimab with 5-FU/leucovorin and celecoxib. All patients will be evaluated every four cycles of treatment using imaging CT/MRI. The primary objective is to assess the objective response rate (ORR) per RECIST 1.1, with secondary endpoints including progression-free survival (PFS), disease control rate (DCR), safety profile, and exploratory biomarkers .
- Conditions
- Colorectal Cancer
- Being tested
- Ivonescimab +mFOLFOXIRI +celecoxib
- Keywords
- BRAF V600E mutation
- Medical subject headings
- Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ivonescimab +mFOLFOXIRI +celecoxibDrug
Also called Oxaliplatin, Irinotecan, 5-Fluorouracil, Leucovorin
Ivonescimab（AK112）10mg/kg, intravenously for 60 minutes, followed by mFOLFOXIRI (oxaliplatin 85 mg/m2, irinotecan 150 mg/m2, and folinic acid 400 mg/m2 followed by 5-fluorouracil 2400mg/m2 as a 46-hour continuous infusion on day 1) every 2 weeks, celecoxib 400mg oral everyday.
| Study group | Role | What they receive |
|---|---|---|
| Ivonescimab +mFOLFOXIRI +celecoxib | Experimental | Patients receive Ivonescimab and mFOLFOXIRI on day1 of every two weeks and celecoxib on day 1-14 of every two weeks Receives: Drug: Ivonescimab +mFOLFOXIRI +celecoxib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Objective response rate (ORR)
Defined as the proportion of patients who are assessed for best overall response as complete response (CR) or partial response (PR) according to RECIST version 1.1. If the response reaches CR or PR, it must be confirmed at least 4 weeks (28 days) after the initial evaluation.
Measured: 3 years
Secondary outcomes (4)
Disease control rate (DCR)
Defined as the proportion of patients who are assessed for best overall response as CR or PR or stable disease (SD) according to RECIST version 1.1.
Measured: 3 years
Progression-free survival (PFS)
Defined as the time from enrollment to the first documented tumor progression (assessed according to RECIST version 1.1, regardless of whether treatment continues) or the date of death from any cause, whichever occurs first.
Measured: 3 years
Overall survival (OS)
Defined as the time from enrollment to death from any cause.
Measured: 3 years
Number of participants with treatment-related adverse events as assessed by CTCAE v5.0
Number of participants with treatment-related adverse events as assessed by CTCAE v5.0
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 posted9 Sep 2026
- Study start10 Aug 2026
- Primary completion31 Dec 2027 (estimated)
- Study completion30 Jun 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Colorectal CancerStudies 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
- 45 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
- Investigators
- Yanhong Deng, Principal investigator, Sixth Affiliated Hospital, Sun Yat-sen University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07809893
- Sponsor's protocol ID
- CSWOG-C11
- Status last verified
- Sep 2026
- First submitted
- 28 Jan 2026
- Last updated
- 9 Sep 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 9 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Ivosidenib Plus mFOLFOXIRI and Celecoxib as a Treatment for BRAF-targeted Therapy-refractory BRAF V600E-mutant Colorectal Cancer Patients: a Phase II Study
- ClinicalTrials.gov ID
- NCT07809893
- Acronym / sponsor ID
- CSWOG-C11
- Conditions
- Colorectal Cancer
- Keywords
- BRAF V600E mutation
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 45 participants (estimated)
- Lead sponsor
- Sun Yat-sen UniversityUniversity, hospital or other
- Study start
- 10 Aug 2026 (actual)
- Primary completion
- 31 Dec 2027 (estimated)
- Study completion
- 30 Jun 2028 (estimated)
- First posted
- 9 Sep 2026 (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-mutated colorectal cancer, primarily driven by the BRAF V600E mutation, accounts for approximately 5-10% of all colorectal cancer cases and is associated with aggressive disease progression and poor prognosis, particularly in metastatic settings. Following first- and second-line treatments, including chemotherapy and targeted therapy, the median overall survival of patients is typically less than 24 months, and tumor progression is rapid once resistance develops. Previous studies have demonstrated that immune checkpoint inhibitors, such as anti-PD-1 therapies, show limited efficacy in microsatellite-stable (MSS) colorectal cancers but may hold promise when combined with other agents to overcome resistance mechanisms. Ivonescimab, a bispecific antibody targeting PD-1 and VEGF, has shown antitumor activity in various solid tumors by simultaneously inhibiting immune evasion and angiogenesis. The combination of ivonescimab with intensive chemotherapy like FOLFOXIRI (folinic acid, 5-fluorouracil, oxaliplatin, and irinotecan) and the COX-2 inhibitor celecoxib aims to enhance antitumor immunity, reduce inflammation, and improve vascular normalization in resistant tumors. However, there are no reported studies on this specific combination for chemotherapy- and BRAF inhibitor-resistant BRAF-mutated colorectal cancer. Therefore, the aim of this study is to evaluate the efficacy and safety of ivonescimab combined with FOLFOXIRI and celecoxib in patients with chemotherapy- and BRAF inhibitor-resistant BRAF-mutated advanced colorectal cancer, with a focus on assessing objective response rate (ORR) and tolerability.
Detailed description
This study is a prospective, investigator-initiated, single-arm, phase II trial to evaluate the efficacy and safety of ivonescimab (AK112) combined with FOLFOXIRI and celecoxib in patients with BRAF-mutated advanced/metastatic colorectal cancer who have developed resistance to prior chemotherapy and BRAF inhibitors . The inclusion criteria: histologically confirmed BRAF V600E-mutated advanced or metastatic colorectal cancer; documented resistance/progression after at least one line of standard chemotherapy ( FOLFOX/FOLFIRI-based) and BRAF inhibitor-based targeted therapy; measurable disease per RECIST 1.1; ECOG performance status 0-1; adequate organ function; no active brain metastases or other uncontrolled comorbidities (specific criteria can be supplemented as needed). Patients received ivonescimab combined with mFOLFOXIRI (modified FOLFOXIRI regimen) and celecoxib for up to 6-8 cycles or until progression/toxicity, followed by maintenance therapy of continued ivonescimab with 5-FU/leucovorin and celecoxib. All patients will be evaluated every four cycles of treatment using imaging CT/MRI. The primary objective is to assess the objective response rate (ORR) per RECIST 1.1, with secondary endpoints including progression-free survival (PFS), disease control rate (DCR), safety profile, and exploratory biomarkers .
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Ivonescimab +mFOLFOXIRI +celecoxib | Experimental | Drug: Ivonescimab +mFOLFOXIRI +celecoxibPatients receive Ivonescimab and mFOLFOXIRI on day1 of every two weeks and celecoxib on day 1-14 of every two weeks |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Signed the informed consent form voluntarily.
- Aged 18-70.
- Colorectal adenocarcinoma with definite histological evidence, with evidence of distant metastasis;
- Diagnosed with colon or rectal adenocarcinoma, with evidence of distant metastasis;
- Genetic testing indicates a BRAF V600E mutation;
Key exclusion criteria (13 listed)
- Prior to enrollment, ctDNA testing shows known KRAS mutation, NRAS mutation, or ERBB2 gene amplification; tumor tissue testing shows mismatch repair gene deficiency or high microsatellite instability, KRAS mutation, NRAS mutation, or ERBB2 gene amplification;
- Presence of intestinal obstruction, active bleeding, or intestinal perforation requiring emergency intervention;
- Underwent major surgery or severe trauma in the previous 4 weeks;
- Active coronary artery disease, severe/unstable angina, or newly diagnosed angina or myocardial infarction within 12 months prior to study participation;
- Occurrence of thrombotic or embolic events within the past 6 months;
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 |
|---|---|---|
| Ivonescimab +mFOLFOXIRI +celecoxibAlso: Oxaliplatin, Irinotecan, 5-Fluorouracil, LeucovorinIvonescimab（AK112）10mg/kg, intravenously for 60 minutes, followed by mFOLFOXIRI (oxaliplatin 85 mg/m2, irinotecan 150 mg/m2, and folinic acid 400 mg/m2 followed by 5-fluorouracil 2400mg/m2 as a 46-hour continuous infusion on day 1) every 2 weeks, celecoxib 400mg oral everyday. | Drug | Ivonescimab +mFOLFOXIRI +celecoxib |
Primary outcome
Objective response rate (ORR)
Time frame: 3 years
Defined as the proportion of patients who are assessed for best overall response as complete response (CR) or partial response (PR) according to RECIST version 1.1. If the response reaches CR or PR, it must be confirmed at least 4 weeks (28 days) after the initial evaluation.
4 secondary outcomes
Disease control rate (DCR)
Time frame: 3 years
Progression-free survival (PFS)
Time frame: 3 years
Overall survival (OS)
Time frame: 3 years
Number 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 9 Sep 2026.
- Individual participant dataSharing planned: Undecided
Related trials for Colorectal Cancer
Not yet recruitingPhase 1
Hepatic Artery Infusion of Carfilzomib in Participants With Liver Metastatic Disease Previously Treated With Hepatic Artery Infusion Pump Therapy
Colorectal Neoplasms, Neoplasms
Active, not recruiting
Streamlined Geriatric and Oncological Evaluation Based On IC Technology
Breast Cancer, Comorbidities and Coexisting Conditions
RecruitingObservational study
Pre- and On-treatment Multi-omics Profiling of Locally Advanced Rectal Cancer
Rectal Neoplasms
Enrolling by invitationObservational study
Natural History Study of Early Life Exposures in Agriculture (ELEA)
Prostate Cancer, Leukemia
RecruitingPhase 2
Tislelizumab in People With Colorectal Cancer
Colorectal Cancer
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.
Yanhong Deng principal investigator
Sixth Affiliated Hospital, Sun Yat-sen University
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 Ivonescimab +mFOLFOXIRI +celecoxib in people with Colorectal Cancer, 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 11 inclusion and 13 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: looking for participants now, as of the sponsor's last update on 9 Sep 2026. 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, M.D. (00862019325106525, dengyanh@mail.sysu.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Objective response rate (ORR) (time frame: 3 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 9 Sep 2026.