Encorafenib + Cetuximab + Nivolumab for Colorectal Cancer

Overseen By Van K. Morris

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: M.D. Anderson Cancer Center

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 2

Duration: 28 days per cycle

38 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase I/II trial studies the best dose and side effects of encorafenib, cetuximab, and nivolumab and how well they work together in treating patients with microsatellite stable, BRAFV600E gene mutated colorectal cancer that cannot be removed by surgery (unresectable) or has spread to other places in the body (metastatic). Encorafenib and cetuximab may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread.Giving encorafenib, cetuximab, and nivolumab may work better in treating patients with colorectal cancer compared to cetuximab alone.

Research Team

Van K. Morris

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

Adults with microsatellite stable, BRAFV600E mutated colorectal cancer that's inoperable or has spread can join. They must be able to take pills, have certain blood and organ function levels, not be pregnant or fathering a child, and agree to use contraception. Exclusions include HIV, hepatitis B/C infection, uncontrolled hypertension, recent live vaccines, certain heart conditions, brain metastases symptoms.

Inclusion Criteria

Absolute neutrophil count (ANC) ≥ 1.0 x 109/L,

My kidney function, measured by creatinine levels, is within the normal range.

My blood tests show my organs and bone marrow are working well.

Exclusion Criteria

My stomach or intestines do not work well, affecting how I absorb medicine.

I have previously been treated with a BRAF, MEK, or ERK inhibitor.

I had severe side effects from previous cancer treatments targeting specific genes.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive encorafenib orally once daily, cetuximab intravenously on days 1 and 15, and nivolumab intravenously on day 1. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

28 days per cycle

2 visits (in-person) per cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment completion at 30 and 100 days, at 3 months, and then every 3 months thereafter.

Up to 5 years

Multiple visits (in-person)

Treatment Details

Interventions

• Cetuximab
• Encorafenib
• Nivolumab

Trial Overview The trial is testing the combination of encorafenib (blocks enzymes for cell growth), cetuximab (stops tumor cells), and nivolumab (boosts immune attack on cancer) in patients with specific colorectal cancer. It aims to find the best dose and observe side effects compared to using cetuximab alone.

Participant Groups

Group I: Treatment (encorafenib, cetuximab, nivolumab) Experimental Treatment 3 Interventions

Patients receive encorafenib PO QD on days 1-28, cetuximab IV over 1 hour on days 1 and 15, and nivolumab IV over 30 minutes on day 1. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Cetuximab is already approved in United States, European Union for the following indications:

Approved in United States as Erbitux for:

• Locally or regionally advanced squamous cell carcinoma of the head and neck
• Recurrent locoregional disease or metastatic squamous cell carcinoma of the head and neck
• K-Ras wild-type, EGFR-expressing, metastatic colorectal cancer
• BRAF V600E mutation-positive metastatic colorectal cancer

Approved in European Union as Erbitux for:

• Squamous cell carcinoma of the head and neck
• K-Ras wild-type, EGFR-expressing, metastatic colorectal cancer

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+