OncoMatch/Clinical Trials/NCT07809893
Ivosidenib Plus mFOLFOXIRI and Celecoxib for BRAF-targeted Therapy-refractory BRAF V600E-mutant Colorectal Cancer Patients
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
Is NCT07809893 recruiting? Yes, currently enrolling (Oct 2026). This Phase 2 trial studies Ivonescimab +mFOLFOXIRI +celecoxib for colorectal cancer.
Treatment: Ivonescimab +mFOLFOXIRI +celecoxib — 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.
Check if I qualifyExtracted eligibility criteria
Treatments studied
Other
Cancer type
Colorectal Cancer
Biomarker criteria
Required: BRAF v600e
Genetic testing indicates a BRAF V600E mutation
Excluded: KRAS mutation
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
Excluded: NRAS mutation
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
Excluded: HER2 (ERBB2) amplification
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
Excluded: MSH2 loss
tumor tissue testing shows mismatch repair gene deficiency or high microsatellite instability
Excluded: MLH1 loss
tumor tissue testing shows mismatch repair gene deficiency or high microsatellite instability
Excluded: MSH6 loss
tumor tissue testing shows mismatch repair gene deficiency or high microsatellite instability
Excluded: PMS2 loss
tumor tissue testing shows mismatch repair gene deficiency or high microsatellite instability
Disease stage
Metastatic disease required
Demographics
Prior therapy
Must have received: systemic chemotherapy (FOLFOX, CAPOX, FOLFIRI, CAPIRI) — first-line
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
Must have received: BRAF inhibitor (vemurafenib, dabrafenib, encorafenib)
Previously received anti-BRAF V600E targeted therapy and failed, including but not limited to vemurafenib, dabrafenib, and encorafenib
Cannot have received: anti-PD-1 therapy
Previous treatment with programmed cell death protein-1 (PD-1) and its ligand (PD-L1) inhibitors
Cannot have received: anti-PD-L1 therapy
Previous treatment with programmed cell death protein-1 (PD-1) and its ligand (PD-L1) inhibitors
Cannot have received: anti-CTLA-4 therapy
Previous treatment with ... anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) antibodies
Lab requirements
Blood counts
neutrophil count ≥1.5×10^9/L, platelet count ≥75×10^9/L
Kidney function
serum creatinine ≤2.5×UNL
Liver function
serum total bilirubin ≤1.5× upper limit of normal value (UNL), aspartate transferase ≤2.5×UNL, alanine transferase ≤2.5×UNL
Adequate organ function: neutrophil count ≥1.5×10^9/L, platelet count ≥75×10^9/L, serum total bilirubin ≤1.5× UNL, aspartate transferase ≤2.5×UNL, alanine transferase ≤2.5×UNL, serum creatinine ≤2.5×UNL
Structured fields extracted by AI. May contain errors — verify against the official protocol.
Frequently asked questions
Is NCT07809893 currently recruiting?
Yes, this trial is currently recruiting patients.
Are there prior therapy exclusions?
Yes. Prior anti-PD-1 therapy, anti-PD-L1 therapy, anti-CTLA-4 therapy disqualifies patients from enrollment.
Does this trial require BRAF?
Yes, BRAF v600e is a required biomarker for enrollment.
Are patients with KRAS alterations eligible?
No. KRAS mutation is an exclusion criterion.
Are patients with NRAS alterations eligible?
No. NRAS mutation is an exclusion criterion.
Is there an age limit?
Yes. Patients must be 70 years or younger.
Could you qualify for this trial?
Enter your biomarker results to see how this trial's eligibility criteria match your specific cancer profile.
Check if I qualifyRelated pages