Safety and Efficacy of IB-FOLFIRI in BRAF V600E-Mutant Metastatic Colorectal Cancer

NCT07150247 | Recruiting Phase 2

• 1 other identifier: IB-FOLFIRI
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to learn if Iparomlimab and Tuvonralimab combined with bevacizumab and FOLFIRI (IB-FOLFIRI) is safe and effective in treating adults with BRAF V600E-mutant metastatic colorectal cancer (mCRC). The main questions it aims to answer are: Does IB-FOLFIRI improve clinical outcomes compared with historical outcomes in this population? What is the safety profile of IB-FOLFIRI in patients with BRAF V600E-mutant mCRC? Participants will: Receive Iparomlimab and Tuvonralimab, bevacizumab, and FOLFIRI every two weeks Have blood samples and/or tumor tissue collected for biomarker analysis (e.g., ctDNA sequencing) Undergo regular imaging and clinical evaluations to assess treatment response and safety

Conditions

BRAF V600 Colorectal Cancer

Keywords

Objective response rate; Circulating tumor DNA; Phase II clinical trial; BRAF V600E colorectal cancer

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate

  The percentage of patients in a study group who have a partial or complete response to treatment according to RECIST v1.1 criteria

  Assessed after every 4 cycles (each cycle is 2 weeks) from treatment initiation until radiographic disease progression, treatment discontinuation, or completion of the 3-year follow-up, whichever occurs first

Secondary Outcomes (3)

• Progression Free Survival

  Assessed throughout the study duration (3 years)

• Overall survival

  Assessed throughout the study duration (5 years)

• Adverse events

  Assessed throughout the study duration (3 years)

Study Arms (1)

Iparomlimab and Tuvonralimab+ Bevacizumab + FOLFIRI

EXPERIMENTAL

Given every two weeks

Drug: Iparomlimab and Tuvonralimab; Drug: Bevacizumab; Drug: 5-Fluorouracil; Drug: Irinotecan (drug)

Interventions

Iparomlimab and Tuvonralimab DRUG

3mg/kg，ivdrip

Also known as: QL1706

Iparomlimab and Tuvonralimab+ Bevacizumab + FOLFIRI

Bevacizumab DRUG

5mg/kg，ivdrip

Also known as: Avastin

Iparomlimab and Tuvonralimab+ Bevacizumab + FOLFIRI

5-Fluorouracil DRUG

400mg/m2 iv followed by 2.4g/m2 civ 48h

Also known as: 5-FU

Iparomlimab and Tuvonralimab+ Bevacizumab + FOLFIRI

Irinotecan (drug) DRUG

180mg/m2

Also known as: CPT-11

Iparomlimab and Tuvonralimab+ Bevacizumab + FOLFIRI

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥18 years and ≤75 years
• Histologically confirmed metastatic colorectal adenocarcinoma
• BRAF V600E mutation confirmed by tissue pathology or ctDNA testing (PCR or NGS)
• Disease progression after at least one line of treatment: FOLFOX/XELOX (oxaliplatin-based doublet) ± bevacizumab or FOLFOXIRI (irinotecan-based triplet) ± bevacizumab. Note: Irinotecan must not have failed during prior treatment, and disease must not have progressed within three months of stopping treatment
• Patients who have received first-line treatment with cetuximab combined with a BRAF inhibitor (e.g., encorafenib, dabrafenib, vemurafenib) are allowed
• At least one measurable lesion according to RECIST v1.1 criteria
• Adequate hematologic unction: Platelets \> 90 × 10⁹/L; Hemoglobin \> 100 g/L; White blood cells \> 3 × 10⁹/L; Neutrophils \> 1.5 × 10⁹/L; Adequate liver function; Total bilirubin ≤ 1.5 × ULN; AST and ALT ≤ 2.5 × ULN (≤ 5 × ULN if liver metastases present); Alkaline phosphatase ≤ 2.5 × ULN; No ascites; Coagulation: PT ≤ 1.5 × ULN, INR ≤ 1.5 × ULN, APTT ≤ 1.5 × ULN, Albumin ≥ 30 g/L
• Adequate renal function: CrCl ≥ 50 mL/min or serum creatinine ≤ 1.5 × ULN
• Liver function Child-Pugh class A
• ECOG performance status 0-1
• Expected survival \> 3 months
• Signed written informed consent
• Willing and able to comply with follow-up until death, study completion, or study termination
• For women of childbearing potential: Negative serum pregnancy test within 14 days prior to treatment; Willing to use medically accepted contraception during the study and for 3 months after the last dose
• For male participants with partners of childbearing potential: Must have undergone surgical sterilization, or use effective contraception during the study and for 3 months after the last dose

You may not qualify if:

• KRAS or NRAS mutation
• MSI-H/dMMR patients
• Prior treatment with PD-1, PD-L1, or CTLA-4 inhibitors
• Known contraindications to irinotecan at the planned dose
• Use of systemic immunosuppressive drugs within 1 week prior to treatment
• Active autoimmune disease requiring treatment, or history of such disease within the past 2 years
• Known primary immunodeficiency
• History of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation
• Retinal vein occlusion or risk factors for retinal vein occlusion (e.g., uncontrolled glaucoma or high intraocular pressure)
• History of acute or chronic pancreatitis
• Chronic inflammatory bowel disease or Crohn's disease requiring medical intervention (immunomodulatory, immunosuppressive therapy, or surgery) within 12 months prior to enrollment
• Gastrointestinal disorders that may significantly affect oral drug absorption (e.g., severe GI ulcers, uncontrolled vomiting, malabsorption syndrome, short bowel syndrome)
• Neuromuscular diseases associated with elevated CK (e.g., inflammatory myopathy, muscular dystrophy, amyotrophic lateral sclerosis, spinal muscular atrophy)
• Residual ≥Grade 2 toxicity from prior anti-tumor therapy (excluding ≥Grade 2 alopecia or neuropathy)
• History of HIV infection

Sponsors & Collaborators

• Sun Yat-sen University: lead

Study Sites (1)

Sun Yat-sen University Cancer Center

Guangzhou, Guangdong, 510060, China

RECRUITING

MeSH Terms

Interventions

Bevacizumab; Fluorouracil; Irinotecan; Pharmaceutical Preparations

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Camptothecin; Alkaloids

Central Study Contacts

Deshen Wang, PhD

CONTACT

87342487; wangdsh@sysucc.org.cn

Ruihua Xu, PhD

CONTACT

87342479; xurh@sysucc.org.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: Prospecitve Single arm study

Study Record Dates

• First Submitted: August 25, 2025
• First Posted: September 2, 2025
• Study Start: June 1, 2025
• Primary Completion (Estimated): June 30, 2027
• Study Completion (Estimated): June 30, 2028
• Last Updated: September 26, 2025

Record last verified: 2025-09

Locations

CN (1)