Colorectal Cancer MetastaticPhase 3FIRBITNCT07729605
FOLFIRI Plus Bevacizuamb and QL1706 in Second-Line Treatment for mCRC
A Phase 3 study testing FOLFIRI + bevacizumab + QL1706 and FOLFIRI + bevacizumab in people with Colorectal Cancer Metastatic and Microsatellite Stable (MSS) Colorectal Cancer (CRC), run by Sun Yat-sen University at 1 site in China.
Trial summary
Thsi study is a randomised, parallel-controlled phase II/III trial evaluating FOLFIRI plus bevacizumab with or without QL1706 as second-line therapy for metastatic colorectal cancer. The primary endpoint is PFS. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Colorectal Cancer Metastatic, Microsatellite Stable (MSS) Colorectal Cancer (CRC)
- What is being tested?
- FOLFIRI + bevacizumab + QL1706 and FOLFIRI + bevacizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 270 participants
- Where
- 1 siteChina
- Study dates
- 30 Jul 2026to 30 Jul 2029
- Phase
- Phase 3
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 1. Willing and able to provide written informed consent. 2. Age ≥ 18 years old. 3.Histologically confirmed metastatic colorectal adenocarcinoma with pMMR/MSS status. 4. Eastern Cooperative Oncology Group (ECOG) performance status 0-2. 5.Discontinued first-line oxaliplatin-based doublet chemotherapy for metastatic colorectal cancer due to intolerable toxicities or disease progression; OR developed recurrent metastatic disease within 6 months after the last dose of adjuvant chemotherapy. 6.Presence of evaluable lesions on imaging examinations. 7. Adequate bone marrow, hepatic and renal function as assessed by the following laboratory requirements conducted within 7 days of starting study treatment. 8.Willing and able to comply with study procedures and scheduled visit schedules
Who cannot join
- 1.Patients complicated with digestive tract diseases including duodenal ulcer, ulcerative colitis, intestinal obstruction, or other conditions judged by the investigator to potentially cause gastrointestinal hemorrhage or perforation; or massive pleural effusion or ascites requiring intervention. 2.Previous or concurrent cancer that is distinct in primary site or histology from colon cancer within 5 years prior to randomization. 3. Radiological evidence of brain metastases. 4. Prior treatment with irinotecan hydrochloride, or prior receipt of PD-1 and/or CTLA-4 immunotherapy in the first-line setting. 5. Autoimmune diseases requiring continuous systemic steroid therapy. 6. History of laparotomy, thoracotomy or intestinal resection within 28 days prior to enrollment; or unhealed wounds (excluding suture wounds from central venous catheter implantation), gastrointestinal ulcers or traumatic fractures. 7. Any of the following events occurring within 12 months before study enrollment: myocardial infarction, severe/unstable angina pectoris, New York Heart Association (NYHA) class ≥ 2 cardiac insufficiency, clinically significant supraventricular or ventricular arrhythmias, and symptomatic congestive heart failure. 8.Confirmed human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome (AIDS)-related diseases. 9. Active inflammatory bowel disease or other colorectal diseases causing chronic diarrhea; interstitial lung disease, non-infectious pneumonia, or uncontrolled systemic diseases (e.g., diabetes mellitus, hypertension, pulmonary fibrosis, acute pneumonia, etc.). 10. Breastfeeding or pregnant women; lack of effective contraceptive. 11. Other severe physical or psychiatric illnesses, or laboratory abnormalities that may increase the risks of study participation or interfere with study outcomes; or patients deemed unsuitable for this study by the investigator.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Jianwei Zhang, doctor contact
China1 site
The sixth affiliated hospital of Sun Yat-sen University
Guangzhou, Guangdong
Yanhong Deng, PhD, 86-13925106525, dengyanh@mail.sysu.edu.cn
Yanhong Deng, PhD
About this study
Official title: FOLFIRI Plus Bevacizuamb With or Without Iparomlimab and Tuvonralimab as Second-Line Treatment for Metastatic Colorectal Cancer: A Randomized Controlled Trial
Thsi study is a randomised, parallel-controlled phase II/III trial evaluating FOLFIRI plus bevacizumab with or without QL1706 as second-line therapy for metastatic colorectal cancer. The primary endpoint is PFS. Secondary endpoint includes overall survival, objective response rate, safety profiles, immune-related adverse events, and patient quality of life. Exploratory analyses focus on dynamic shifts in tumour immune microenvironment and biomarkers, aiming to identify predictive signatures for therapeutic efficacy and immune toxicities.
Read the detailed description
This is a prospective, randomised, parallel-controlled phase II/III clinical trial designed to investigate the efficacy and safety of adding QL1706, a dual PD-1/CTLA-4 bispecific immune checkpoint inhibitor, to the standard second-line FOLFIRI plus bevacizumab regimen in patients with metastatic colorectal cancer. Eligible participants who have progressed after first-line oxaliplatin-based systemic therapy will be randomly assigned to either the experimental group receiving combination treatment with FOLFIRI, bevacizumab and QL1706 or the control group treating with FOLFIRI plus bevacizumab alone, to conduct head-to-head comparative analysis of clinical outcomes. The primary endpoint of the trial is progression-free survival. Secondary endpoints comprehensively evaluating overall survival, objective response rate, disease control rate, the incidence and severity of treatment-related adverse events and immune-related adverse events. Exploratory analyses are pre-specified in this trial. Serial detection and dynamic analysis of tumour immune microenvironment characteristics and multiple peripheral biomarkers will be performed to clarify the immunomodulatory effect of the triple combination regimen. Furthermore, correlative analyses will be conducted to screen and validate potential predictive signatures, including immune cell subsets, cytokine profiles and molecular biomarkers, for clinical treatment response and immune-related toxicities, aiming to provide precise evidence for individualised second-line immunotherapy combined with targeted chemotherapy for metastatic colorectal cancer.
- Being tested
- FOLFIRI + bevacizumab + QL1706, FOLFIRI + bevacizumab
- Keywords
- PD-1/CTLA-4, QL1706, Bevacizumab, FOLFIRI, Second-line
- Medical subject headings
- Spinocerebellar Degenerations, Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FOLFIRI + bevacizumab + QL1706Drug
Also called QL1706, Irinotecan, 5-Fluorouracil, Leucovorin
QL1706 (4mg/kg on day 1), Bevacizumab (5 mg/kg on day 1) plus mFOLFIRI ( irinotecan 180 mg/m2, and folinic acid 400 mg/m2 followed by bolus 5-fluorouracil 400 mg/m2 and 5-fluorouracil 2400mg/m2 as a 46-hour continuous infusion on day 1) for 8 cycles and followed by QL1706 plus bevacizumab and fluoropyrimidine based maintence treatment.
FOLFIRI + bevacizumabDrug
Also called Bevacizumab, 5-Fluorouracil, Leucovorin, Irinotecan
Bevacizumab (5 mg/kg on day 1) plus mFOLFIRI ( irinotecan 180 mg/m2, and folinic acid 400 mg/m2 followed by bolus 5-fluorouracil 400 mg/m2 and 5-fluorouracil 2400mg/m2 as a 46-hour continuous infusion on day 1) for 8 cycles and followed by bevacizumab and fluoropyrimidine based maintence treatment.
| Study group | Role | What they receive |
|---|---|---|
| Experimental: FOLFIRI + Bevacizumab + QL1706 | Experimental | Patients will receive FOLFIRI plus Bevacizumab and QL1706, repeat once every 2 weeks. After 8 cycles of induction therapy, patients without disease progression will receive 5-FU, bevacizumab and QL1706 as maintenance therapy till disease progression. Receives: Drug: FOLFIRI + bevacizumab + QL1706 |
| Control: FOLFIRI + Bevacizumab | Active comparator | Patients will receive FOLFIRI plus Bevacizumab, repeat once every 2 weeks. After 8 cycles of induction therapy, patients without disease progression will receive 5-FU and bevacizumab as maintenance therapy till disease progression. Receives: Drug: FOLFIRI + bevacizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression-free survival (PFS)
The PFS is defined as the time from the start of treatment to the date of first documented PD or death as a result of any cause, whichever occurred first.
Measured: 2 years
Secondary outcomes (3)
Objective response rate (ORR)
The percentage of subjects with total number of Complete Response (CR) + total number of Partial Response (PR)
Measured: 2 years
Overall Survival (OS)
OS is defined as the time from date of randomization to death due to any cause. Subjects still alive at the time of analysis were censored at their last date of last contact.
Measured: 5 years
Toxicity assessed using the NCI common toxicity criteria, version 5.0.
The grade of toxicity will be assessed using the NCI common toxicity criteria, version 5.0.
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jul 2026
- Study start30 Jul 2026 (estimated)
- Primary completion30 Dec 2028 (estimated)
- Study completion30 Jul 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Colorectal Cancer MetastaticStudies 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Prospective, parallel control, Phase 3
- Masking
- None (open label)
- Enrolment
- 270 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, PhD, Principal investigator, Sixth Affiliated Hospital, Sun Yat-sen University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07729605
- Sponsor's protocol ID
- CSWOG-C12
- Acronym
- FIRBIT
- Status last verified
- Jul 2026
- First submitted
- 22 Jul 2026
- Last updated
- 27 Jul 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 27 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- FOLFIRI Plus Bevacizuamb With or Without Iparomlimab and Tuvonralimab as Second-Line Treatment for Metastatic Colorectal Cancer: A Randomized Controlled Trial
- ClinicalTrials.gov ID
- NCT07729605
- Acronym / sponsor ID
- FIRBIT / CSWOG-C12
- Keywords
- PD-1/CTLA-4, QL1706, Bevacizumab, FOLFIRI, Second-line
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 270 participants (estimated)
- Lead sponsor
- Sun Yat-sen UniversityUniversity, hospital or other
- Study start
- 30 Jul 2026 (estimated)
- Primary completion
- 30 Dec 2028 (estimated)
- Study completion
- 30 Jul 2029 (estimated)
- First posted
- 27 Jul 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.
Thsi study is a randomised, parallel-controlled phase II/III trial evaluating FOLFIRI plus bevacizumab with or without QL1706 as second-line therapy for metastatic colorectal cancer. The primary endpoint is PFS. Secondary endpoint includes overall survival, objective response rate, safety profiles, immune-related adverse events, and patient quality of life. Exploratory analyses focus on dynamic shifts in tumour immune microenvironment and biomarkers, aiming to identify predictive signatures for therapeutic efficacy and immune toxicities.
Detailed description
This is a prospective, randomised, parallel-controlled phase II/III clinical trial designed to investigate the efficacy and safety of adding QL1706, a dual PD-1/CTLA-4 bispecific immune checkpoint inhibitor, to the standard second-line FOLFIRI plus bevacizumab regimen in patients with metastatic colorectal cancer. Eligible participants who have progressed after first-line oxaliplatin-based systemic therapy will be randomly assigned to either the experimental group receiving combination treatment with FOLFIRI, bevacizumab and QL1706 or the control group treating with FOLFIRI plus bevacizumab alone, to conduct head-to-head comparative analysis of clinical outcomes. The primary endpoint of the trial is progression-free survival. Secondary endpoints comprehensively evaluating overall survival, objective response rate, disease control rate, the incidence and severity of treatment-related adverse events and immune-related adverse events. Exploratory analyses are pre-specified in this trial. Serial detection and dynamic analysis of tumour immune microenvironment characteristics and multiple peripheral biomarkers will be performed to clarify the immunomodulatory effect of the triple combination regimen. Furthermore, correlative analyses will be conducted to screen and validate potential predictive signatures, including immune cell subsets, cytokine profiles and molecular biomarkers, for clinical treatment response and immune-related toxicities, aiming to provide precise evidence for individualised second-line immunotherapy combined with targeted chemotherapy for metastatic colorectal cancer.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Prospective, parallel control, Phase 3
| Arm | Type | Receives |
|---|---|---|
| Experimental: FOLFIRI + Bevacizumab + QL1706 | Experimental | Drug: FOLFIRI + bevacizumab + QL1706Patients will receive FOLFIRI plus Bevacizumab and QL1706, repeat once every 2 weeks. After 8 cycles of induction therapy, patients without disease progression will receive 5-FU, bevacizumab and QL1706 as maintenance therapy till disease progression. |
| Control: FOLFIRI + Bevacizumab | Active comparator | Drug: FOLFIRI + bevacizumabPatients will receive FOLFIRI plus Bevacizumab, repeat once every 2 weeks. After 8 cycles of induction therapy, patients without disease progression will receive 5-FU and bevacizumab as maintenance therapy till disease progression. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- 1. Willing and able to provide written informed consent. 2. Age ≥ 18 years old. 3.Histologically confirmed metastatic colorectal adenocarcinoma with pMMR/MSS status. 4. Eastern Cooperative Oncology Group (ECOG) performance status 0-2. 5.Discontinued first-line oxaliplatin-based doublet chemotherapy for metastatic colorectal cancer due to intolerable toxicities or disease progression; OR developed recurrent metastatic disease within 6 months after the last dose of adjuvant chemotherapy. 6.Presence of evaluable lesions on imaging examinations. 7. Adequate bone marrow, hepatic and renal function as assessed by the following laboratory requirements conducted within 7 days of starting study treatment. 8.Willing and able to comply with study procedures and scheduled visit schedules
Key exclusion criteria (1 listed)
- 1.Patients complicated with digestive tract diseases including duodenal ulcer, ulcerative colitis, intestinal obstruction, or other conditions judged by the investigator to potentially cause gastrointestinal hemorrhage or perforation; or massive pleural effusion or ascites requiring intervention. 2.Previous or concurrent cancer that is distinct in primary site or histology from colon cancer within 5 years prior to randomization. 3. Radiological evidence of brain metastases. 4. Prior treatment with irinotecan hydrochloride, or prior receipt of PD-1 and/or CTLA-4 immunotherapy in the first-line setting. 5. Autoimmune diseases requiring continuous systemic steroid therapy. 6. History of laparotomy, thoracotomy or intestinal resection within 28 days prior to enrollment; or unhealed wounds (excluding suture wounds from central venous catheter implantation), gastrointestinal ulcers or traumatic fractures. 7. Any of the following events occurring within 12 months before study enrollment: myocardial infarction, severe/unstable angina pectoris, New York Heart Association (NYHA) class ≥ 2 cardiac insufficiency, clinically significant supraventricular or ventricular arrhythmias, and symptomatic congestive heart failure. 8.Confirmed human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome (AIDS)-related diseases. 9. Active inflammatory bowel disease or other colorectal diseases causing chronic diarrhea; interstitial lung disease, non-infectious pneumonia, or uncontrolled systemic diseases (e.g., diabetes mellitus, hypertension, pulmonary fibrosis, acute pneumonia, etc.). 10. Breastfeeding or pregnant women; lack of effective contraceptive. 11. Other severe physical or psychiatric illnesses, or laboratory abnormalities that may increase the risks of study participation or interfere with study outcomes; or patients deemed unsuitable for this study by the investigator.
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 |
|---|---|---|
| FOLFIRI + bevacizumab + QL1706Also: QL1706, Irinotecan, 5-Fluorouracil, LeucovorinQL1706 (4mg/kg on day 1), Bevacizumab (5 mg/kg on day 1) plus mFOLFIRI ( irinotecan 180 mg/m2, and folinic acid 400 mg/m2 followed by bolus 5-fluorouracil 400 mg/m2 and 5-fluorouracil 2400mg/m2 as a 46-hour continuous infusion on day 1) for 8 cycles and followed by QL1706 plus bevacizumab and fluoropyrimidine based maintence treatment. | Drug | Experimental: FOLFIRI + Bevacizumab + QL1706 |
| FOLFIRI + bevacizumabAlso: Bevacizumab, 5-Fluorouracil, Leucovorin, IrinotecanBevacizumab (5 mg/kg on day 1) plus mFOLFIRI ( irinotecan 180 mg/m2, and folinic acid 400 mg/m2 followed by bolus 5-fluorouracil 400 mg/m2 and 5-fluorouracil 2400mg/m2 as a 46-hour continuous infusion on day 1) for 8 cycles and followed by bevacizumab and fluoropyrimidine based maintence treatment. | Drug | Control: FOLFIRI + Bevacizumab |
Primary outcome
Progression-free survival (PFS)
Time frame: 2 years
The PFS is defined as the time from the start of treatment to the date of first documented PD or death as a result of any cause, whichever occurred first.
3 secondary outcomes
Objective response rate (ORR)
Time frame: 2 years
Overall Survival (OS)
Time frame: 5 years
Toxicity assessed using the NCI common toxicity criteria, version 5.0.
Time frame: 2 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 27 Jul 2026.
- Individual participant dataSharing planned: Undecided
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CRC
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.
Jianwei Zhang, doctor contact
Yanhong Deng, PhD 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 3 study testing FOLFIRI + bevacizumab + QL1706 and FOLFIRI + bevacizumab in people with Colorectal Cancer Metastatic and Microsatellite Stable (MSS) 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 1 inclusion and 1 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 27 Jul 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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, PhD (86-13925106525, 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?
Progression-free survival (PFS) (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 27 Jul 2026.