Actively Recruiting
Open-label Phase 2 Study of Avutometinib (RAF/MEK Clamp) in Combination With Defactinib (FAK Inhibitor) and Cetuximab in Patients With Unresectable, Anti-EGFR-Refractory Advanced Colorectal Cancer
Led by M.D. Anderson Cancer Center · Updated on 2026-05-20
33
Participants Needed
1
Research Sites
N/A
Total Duration
On this page
AI-Summary
What this Trial Is About
Researchers are evaluating the combination of avutometinib, defactinib, and cetuximab in patients with unresectable, advanced colorectal cancer that is resistant to anti-EGFR therapies. This open-label Phase 2 study aims to assess the antitumor activity of this treatment combination using standard response criteria and to understand its safety, impact on survival, pharmacodynamics, and mechanisms of resistance. The study also explores biomarkers that might predict treatment response and resistance. Participants will receive the investigational drugs avutometinib (taken orally), defactinib (taken orally), and cetuximab (given by intravenous infusion). The study includes a Safety Run In group where different doses of avutometinib are tested to identify the recommended dose, followed by an Expansion group where all participants receive the selected dose. The Safety Run In involves enrolling 3 to 6 participants per dose level to monitor side effects and tolerability before moving to the Expansion phase. During the study, participants will be monitored regularly for safety and adverse events over about one year. Assessments will include scans to measure tumor response according to RECIST 1.1 criteria, laboratory tests, and evaluations of pharmacodynamics and biomarker levels. Participants must comply with study requirements, including oral medication intake and scheduled visits, to help researchers understand the treatment's effects and safety profile.
CONDITIONS
Brief Title
Open-label Phase 2 Study of Avutometinib (RAF/MEK Clamp) in Combination With Defactinib (FAK Inhibitor) and Cetuximab in Patients With Unresectable, Anti-EGFR-Refractory Advanced Colorectal Cancer
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Provide signed informed consent before any screening procedures
- Age 18 years or older at time of consent
- Diagnosed with adenocarcinoma of colon or rectum that is unresectable or metastatic and measurable by RECIST 1.1
- Tumor or circulating tumor DNA showing KRAS, NRAS, EGFR ectodomain, and BRAF V600E wild-type status
- Prior treatment with at least one systemic chemotherapy regimen for metastatic colorectal cancer or progression within 6 months of adjuvant chemotherapy
- Prior anti-EGFR therapy (cetuximab or panitumumab) for at least 16 weeks with complete or partial response before progression
- ECOG performance status of 0 or 1
- Recovery from acute chemotherapy effects (Grade 1 or less), at least 21 days since last chemotherapy dose
- Recovery from acute radiotherapy effects, at least 7 days since end of radiotherapy
- Adequate blood counts including neutrophils, hemoglobin, and platelets
- Adequate liver function with specified limits on liver enzymes and bilirubin
- Adequate kidney function with serum creatinine or creatinine clearance meeting study requirements
- QTc interval 480 ms or less
- Able to take oral medications
- Female participants of childbearing potential must have negative pregnancy test and use effective contraception; all sexually active participants must be postmenopausal, surgically sterile, or use contraception
- Willing and able to comply with study requirements
- Prior or concurrent malignancy allowed if it does not interfere with safety or study assessments after consultation
You will not qualify if you...
- History of severe allergic reaction or intolerance to cetuximab or panitumumab
- History of allergic reactions to compounds similar to cetuximab or red meat allergy/tick bite history
- Prior treatment with ERK1/2, MEK, or BRAF inhibitors
- Presence of symptomatic brain metastases
- Known leptomeningeal disease
- History or risk of retinal vein occlusion or central serous retinopathy
- Previous or concurrent malignancy within 3 years except certain noninvasive or indolent cancers
- Significant cardiovascular diseases including recent acute coronary syndrome, symptomatic heart failure, serious arrhythmias, uncontrolled hypertension
- Active systemic bacterial or fungal infections requiring intravenous therapy
- Active HIV infection requiring treatment
- Active hepatitis B or C infection with defined criteria
- Gastrointestinal conditions impairing drug absorption
- Any other condition that contraindicates participation due to safety or compliance concerns
- Major surgery within 6 weeks prior to starting study drug or failure to recover
- Systemic anti-cancer therapy within 4 weeks or within 5 half-lives of previous drug
- Pregnant or nursing women
- History of rhabdomyolysis
- Medical, psychiatric, cognitive or other conditions limiting ability to consent, comply, or complete study
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
Your Study Journey
Duration - 2 to 4 weeks
Participants are screened for eligibility to participate in the trial.
1 visit (in-person)
Duration - Up to approximately 1 year or until disease progression or unacceptable toxicity
Participants receive a combination of three drugs: avutometinib (oral), defactinib (oral), and cetuximab (intravenous) to treat unresectable advanced colorectal cancer that has not responded to prior anti-EGFR therapy.
Regular visits for treatment administration and safety monitoring per study protocol
Trial Site Locations
Total: 1 location
1
MD Anderson Cancer Center
Houston, Texas, United States, 77807
Actively Recruiting
Research Team
C
Christine Parseghian, MD
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
NON_RANDOMIZED
Model
SINGLE_GROUP
Primary Purpose
TREATMENT
Number of Arms
2
Similar Trials
Frequently Asked Questions
Have more questions? Get in touch with our team for quick support
Not the Right Trial for You?
Explore thousands of other clinical trials that might be a better match.
Sign up to get personalized trial recommendations delivered to your inbox.
Already have an account? Log in here