Safety and Efficacy of IB-FOLFIRI in BRAF V600E-Mutant Metastatic Colorectal Cancer
A Phase II Single-Arm Study of Iparomlimab and Tuvonralimab Combined With Bevacizumab and FOLFIRI in BRAF V600E-Mutant Metastatic Colorectal Cancer
Sun Yat-sen University
20 participants
Jun 1, 2025
INTERVENTIONAL
Conditions
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
Eligibility
Inclusion Criteria15
- 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
Exclusion Criteria33
- 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
- History of Gilbert's syndrome
- Interstitial pneumonia or extensive symptomatic interstitial pulmonary fibrosis
- Severe uncontrolled systemic comorbidities
- Severe cardiovascular disease, including:
- Stroke within 6 months prior to enrollment
- Myocardial infarction within 6 months prior to enrollment
- Hypertension not controlled with appropriate medications
- Unstable angina
- Congestive heart failure (NYHA class 2-4)
- Cardiac arrhythmias requiring treatment
- Current or prior central nervous system disease, including: Primary brain tumor; Epilepsy not controlled by standard treatment; Any brain metastases or history of stroke
- Other uncontrolled comorbidities, including active bleeding, uncontrolled infection or non-malignant medical conditions that could be worsened by study therapy, or uncontrolled psychiatric/social conditions
- History of other malignancies within the past 5 years (except for curatively treated basal cell carcinoma, cervical carcinoma in situ, or thyroid cancer)
- Allergy to any study drug
- Pregnant or breastfeeding women
- Women of childbearing potential (last menstrual period <2 years) or men who refuse to use effective non-hormonal contraception (IUD, barrier method plus spermicide, or sterilization)
- Inability or unwillingness to comply with study protocol
- Any other disease, metastatic lesion-related functional impairment, or suspicious findings on physical examination that may indicate contraindication to study drug use or place the patient at high risk of treatment-related complications.
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Interventions
3mg/kg，ivdrip
5mg/kg，ivdrip
400mg/m2 iv followed by 2.4g/m2 civ 48h
180mg/m2
Locations(1)
View Full Details on ClinicalTrials.gov
For the most up-to-date information, visit the official listing.
NCT07150247