FOLFIRI Plus Bevacizuamb and QL1706 in Second-Line Treatment for mCRC

NCT07729605 | Not Yet Recruiting Phase 3

• 1 other identifier: CSWOG-C12
• Study Type: interventional
• Target: 270
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Colorectal Cancer Metastatic; Microsatellite Stable (MSS) Colorectal Cancer (CRC)

Keywords

PD-1/CTLA-4; QL1706; Bevacizumab; FOLFIRI; Second-line

Outcome Measures

Primary Outcomes (1)

• 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.

  2 years

Secondary Outcomes (3)

• Objective response rate (ORR)

  2 years

• Overall Survival (OS)

  5 years

• Toxicity assessed using the NCI common toxicity criteria, version 5.0.

  2 years

Study Arms (2)

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.

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.

Drug: FOLFIRI + bevacizumab

Interventions

FOLFIRI + bevacizumab + QL1706 DRUG

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.

Also known as: QL1706, Irinotecan, 5-Fluorouracil, Leucovorin, Bevacizumab

Experimental: FOLFIRI + Bevacizumab + QL1706

FOLFIRI + bevacizumab DRUG

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.

Also known as: Bevacizumab, 5-Fluorouracil, Leucovorin, Irinotecan

Control: FOLFIRI + Bevacizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \. 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Sun Yat-sen University: lead

Study Sites (1)

The sixth affiliated hospital of Sun Yat-sen University

Guangzhou, Guangdong, China

Location

MeSH Terms

Conditions

Spinocerebellar Degenerations; Colorectal Neoplasms

Interventions

Bevacizumab; Irinotecan; Fluorouracil; Leucovorin

Condition Hierarchy (Ancestors)

Cerebellar Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Spinal Cord Diseases; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Camptothecin; Alkaloids; Heterocyclic Compounds; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes

Study Officials

• Yanhong Deng, PhD

  Sixth Affiliated Hospital, Sun Yat-sen University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Yanhong Deng, PhD

CONTACT

86-13925106525; dengyanh@mail.sysu.edu.cn

Jianwei Zhang, doctor

CONTACT

zhangjw25@mail.sysu.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: None (open label)
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: Prospective, parallel control, Phase 3

Study Record Dates

• First Submitted: July 22, 2026
• First Posted: July 27, 2026
• Study Start: July 30, 2026
• Primary Completion (Estimated): December 30, 2028
• Study Completion (Estimated): July 30, 2029
• Last Updated: July 27, 2026

Record last verified: 2026-07

Locations

CN (1)