Ivosidenib plus intensive chemotherapy for BRAF V600E-mutant colorectal cancer after resistance

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

What this trial studies

This is a phase II, single-arm study evaluating the safety and activity of ivonescimab in combination with mFOLFOXIRI and celecoxib in patients whose BRAF V600E-mutant colorectal cancer progressed after prior chemotherapy and BRAF-targeted therapy. Eligible participants have advanced or metastatic disease with measurable lesions and adequate organ function. Treatment cycles continue for up to 6-8 cycles, followed by maintenance therapy, with tumor assessments every four cycles. The study's primary endpoint is objective response rate, with secondary endpoints including progression-free survival, disease control, safety, and exploratory biomarkers.

Why it matters

Who can join: the full rules

Inclusion Criteria:

1. Signed the informed consent form voluntarily.
2. Aged 18-70.
3. Colorectal adenocarcinoma with definite histological evidence, with evidence of distant metastasis;
4. Diagnosed with colon or rectal adenocarcinoma, with evidence of distant metastasis;
5. Genetic testing indicates a BRAF V600E mutation;
6. 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; Previously received anti-BRAF V600E targeted therapy and failed, including but not limited to vemurafenib, dabrafenib, and encorafenib;
7. Patients must have measurable lesions according to the Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1.
8. Adequate organ function based on the following laboratory test values obtained within 7 days prior to treatment: neutrophil count ≥1.5×109/L, platelet count ≥75×109/L, serum total bilirubin ≤1.5× upper limit of normal value (UNL), aspartate transferase ≤2.5×UNL, alanine transferase ≤2.5×UNL, serum creatinine ≤2.5×UNL;
9. Female subjects must be either postmenopausal for at least 1 year, have undergone surgical sterilization at least 6 weeks prior, or must agree to use appropriate contraceptive measures;
10. Male subjects must agree to use appropriate contraceptive measures to prevent their partners from becoming pregnant;
11. Willing and able to comply with research protocols and visit plans.

Exclusion Criteria:

1. Prior to enrollment, 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;
2. Presence of intestinal obstruction, active bleeding, or intestinal perforation requiring emergency intervention;
3. Underwent major surgery or severe trauma in the previous 4 weeks;
4. Active coronary artery disease, severe/unstable angina, or newly diagnosed angina or myocardial infarction within 12 months prior to study participation;
5. Occurrence of thrombotic or embolic events within the past 6 months;
6. New York Heart Association (NYHA) class II or higher congestive heart failure;
7. Human immunodeficiency virus (HIV) infection or known acquired immunodeficiency syndrome (AIDS), untreated active hepatitis;
8. Any active, known, or suspected autoimmune disease.
9. Presence of interstitial lung disease, non-infectious pneumonia, or uncontrolled systemic disease;
10. Any unresolved treatment-related adverse events of grade 2 or higher according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 (excluding peripheral neuropathy, anemia, hair loss, and skin pigmentation);
11. Previous treatment with programmed cell death protein-1 (PD-1) and its ligand (PD-L1) inhibitors or anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) antibodies;
12. Known or suspected history of allergy to any of the related drugs used in the study;
13. Pregnant or breastfeeding women.

Where it's running

• Gastrointestinal Hospital, Sun Yat-sen University
  Guangzhou, Guangdong, China Recruiting

Study contacts

• Principal investigator: Yanhong Deng — Sixth Affiliated Hospital, Sun Yat-sen University
• Study coordinator: Yanhong Deng, M.D.
• Email: dengyanh@mail.sysu.edu.cn
• Phone: 00862019325106525

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How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.