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BRAF NP_004324.2:p.V600EPhase 1/2NCT04017650

Encorafenib, Cetuximab, and Nivolumab in Treating Patients With Microsatellite Stable, BRAFV600E Mutated Unresectable or Metastatic Colorectal Cancer

A Phase 1/2 study testing Cetuximab, Encorafenib and Nivolumab in people with BRAF NP_004324.2:p.V600E and Metastatic Colon Adenocarcinoma, run by M.D. Anderson Cancer Center at 1 site in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial summary

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… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Cetuximab, Encorafenib and Nivolumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
38 participants
Where
1 siteUnited States
Study dates
14 Jun 2019to 30 Dec 2027
Phase
Phase 1/2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Provision of signed Informed Consent prior to any screening procedures being performed. A translator may be used for patients who do not speak or read English.
  • Age ≥ 18 years at the time of informed consent.
  • Histologically (or cytologically) confirmed diagnosis of adenocarcinoma of the colon or rectum, with clinical confirmation of unresectable and/or metastatic disease that is measurable according to RECIST1.1 criteria.
  • Confirmation of BRAFV600E tumor as detected by a CLIA-certified laboratory.
  • Confirmation of MSS status in a CLIA-certified laboratory.
  • Cohort A only: Prior treatment with at least one, but no more than two, systemic chemotherapy regimen(s) for mCRC, or recurrence/progression with development of unresectable or metastatic disease within 6 months of adjuvant chemotherapy for resected colorectal cancer.
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  • Cohort B only: prior treatment with a BRAF, anti-EGFR, MEK, or ERK targeted therapy for treatment of colorectal cancer
  • ECOG performance status < 1
  • Adequate bone marrow, organ function and laboratory parameters:
  • Absolute neutrophil count (ANC) ≥ 1.0 x 109/L,
  • Hemoglobin (Hgb) ≥ 9 g/dL with or without transfusions,
  • Platelets (PLT) ≥ 100 x 109/L without transfusions,
  • AST and/or ALT ≤ 2.5 × upper limit of normal (ULN). If liver metastases are present, then it is acceptable for AST level ≤ 5.0 × ULN, and an ALT level ≤ 5.0 × ULN.
  • Total bilirubin ≤ 1.5 × ULN and < 2 mg/dL Note: Patients who have a total bilirubin level > 1.5 x ULN will be allowed if their indirect bilirubin level is ≤ 1.5 x ULN
  • Serum Creatinine ≤ 1.5 x ULN, or calculated creatinine clearance (determined as per Cockcroft-Gault) ≥ 50mL/min at screening;
  • QTc interval ≤ 480 ms (preferably the mean from triplicate ECGs) ;
  • Able to take oral medications;
  • Female patients are either postmenopausal for at least 1 year, are surgically sterile for at least 6 weeks, or must agree to take appropriate precautions to avoid pregnancy from screening through follow-up if of childbearing potential Note: Permitted contraception methods listed in Section 8.2 should be communicated to the patients and their understanding confirmed. For all females, the pregnancy test result must be negative within 24 hours of starting treatment with nivolumab. Males must agree to take appropriate precautions to avoid fathering a child from screening through 100 days following the end of therapy.

Who cannot join

  • Concurrent corticosteroid therapy or concurrent use of any other immunosuppressive medication (corticosteroid use on study as a pre-medication for IV contrast allergies/reactions is allowed). Subjects who are receiving daily steroid replacement therapy (the equivalent of prednisone ≤10 mg daily) serve as an exception to this rule.
  • Cohort A only: Prior treatment with a BRAF inhibitor, MEK inhibitor, or ERK inhibitor (of note, regorafenib is not considered a BRAF inhibitor for the context of eligibility criteria).
  • Cohort A only: Prior treatment with anti-EGFR therapies.
  • Prior immune checkpoint therapy including, but not limited to, an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody, or any other prior immune-modulating agent administered with antineoplastic intent (monoclonal antibodies used against VEGF are permitted)..
  • Prior allogeneic tissue/solid organ transplant.
  • History of (non-infectious) pneumonitis that has required oral or IV steroids.
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  • Receipt of a live vaccine within 30 days prior to the first administration of study medication.
  • Seasonal flu vaccines that do not contain a live virus are permitted.
  • History of a Grade 3 or 4 allergic reaction attributed to humanized or human monoclonal antibody therapy.
  • Cohort B only: unacceptable toxicity to prior BRAF, EGFR, MEK, or ERK inhibitor therapy that in the discretion of the evaluating physician deems the participant at risk of excessive toxicity
  • Active infection requiring concurrent antibiotic use.
  • Any symptomatic brain metastasis. Note: Patients previously treated or untreated for this condition who are asymptomatic in the absence of corticosteroid and anti-epileptic therapy are allowed. Brain metastases must be stable for ≥ 4 weeks, with imaging (e.g., magnetic resonance imaging [MRI] or computed tomography [CT]) demonstrating no current evidence of progressive brain metastases at screening.
  • Leptomeningeal disease
  • Previous or concurrent malignancy within 3 years of study entry, with the following exceptions: adequately treated basal or squamous cell skin cancer, superficial bladder cancer, prostate intraepithelial neoplasm, carcinoma in-situ of the cervix, or other noninvasive or indolent malignancy; other solid tumors treated curatively without evidence of recurrence for at least 3 years prior to study entry.
  • Impaired cardiovascular function or clinically significant cardiovascular diseases, including any of the following:
  • History of acute coronary syndromes (including myocardial infarction, unstable angina, coronary artery bypass grafting, coronary angioplasty, or stenting) <6 months prior to screening,
  • Symptomatic chronic heart failure (i.e. Grade 2 or higher), history or current evidence of clinically significant cardiac arrhythmia and/or conduction abnormality <6 months prior to screening except atrial fibrillation and paroxysmal supraventricular tachycardia;
  • Uncontrolled hypertension defined as persistent elevation of systolic blood pressure ≥ 170 mmHg or diastolic blood pressure ≥ 100 mm Hg, despite current therapy;
  • Known positive serology for HIV (Human immunodeficiency virus), active hepatitis B, and/or active hepatitis C infection;
  • Known history of acute or chronic pancreatitis (history of acute pancreatitis with no recurrent events in the prior 24 months are permitted)
  • Patients with a history of inflammatory bowel disease, including ulcerative colitis and Crohn's disease, are excluded from this study, as are patients with a history of symptomatic autoimmune disease (e.g., rheumatoid arthritis, systemic progressive sclerosis [scleroderma], systemic lupus erythematosus, autoimmune vasculitis [e.g., Wegener's Granulomatosis]); CNS or motor neuropathy considered of autoimmune origin (e.g., Guillain-Barre Syndrome and myasthenia gravis, multiple sclerosis). Patients with Graves' disease will be allowed.
  • Impaired gastrointestinal function or disease that may significantly alter the absorption of study drug (e.g., ulcerative diseases, uncontrolled vomiting, malabsorption syndrome, small bowel resection with decreased intestinal absorption)
  • Any other condition that would, in the Investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns or compliance with clinical study procedures.
  • Major surgery ≤ 6 weeks prior to starting study drug or failure to recover from side effects of such procedure at the discretion of the treating investigator.
  • Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test
  • Medical, psychiatric, cognitive or other conditions, according to clinician judgment, that may compromise the patient's ability to understand the patient information, give informed consent, comply with the study protocol or complete the study.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • M D Anderson Cancer Center

    Houston, Texas, 77030

Other trials in United States

About this study

Official title: Phase I/II Trial of Encorafenib, Cetuximab, and Nivolumab in Microsatellite Stable BRAFV600E Metastatic Colorectal Cancer (BMS-MDACC CA209-8P6/ARRAY IST-818-101X)

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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To describe overall response rate (ORR) upon treatment with encorafenib, cetuximab, and nivolumab.

II. To determine the safety and tolerability of nivolumab, encorafenib, and cetuximab.

SECONDARY OBJECTIVES:

  1. To estimate median progression-free survival (PFS) upon treatment with encorafenib, cetuximab, and nivolumab.

II. To estimate median overall survival (OS) upon treatment with encorafenib, cetuximab, and nivolumab.

III. To estimate median time to response (TTR) upon treatment with encorafenib, cetuximab, and nivolumab.

IV. To estimate median duration of response (DOR) upon treatment with encorafenib, cetuximab, and nivolumab.

  1. To estimate disease control rate (DCR) upon treatment with encorafenib, cetuximab, and nivolumab.

EXPLORATORY OBJECTIVES:

  1. To assess genomic and immune changes upon treatment with encorafenib, cetuximab, and nivolumab.

II. To demonstrate feasibility of establishing humanized patient-derived xenograft models in matched patients with BRAFV600E metastatic colorectal cancer (mCRC).

OUTLINE: This is a phase I, dose-escalation study followed by a phase II study.

Patients receive encorafenib orally (PO) once daily (QD) on days 1-28, cetuximab intravenously (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.

After completion of study treatment, patients are followed up at 30 and 100 days, at 3 months, and then every 3 months thereafter.

Being tested
Cetuximab, Encorafenib, Nivolumab
Medical subject headings
Colonic Neoplasms, Rectal Neoplasms, Disease Progression, Colorectal Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CetuximabBiological

    Also called Cetuximab Biosimilar CDP-1, Cetuximab Biosimilar CMAB009, Cetuximab Biosimilar KL 140, Chimeric Anti-EGFR Monoclonal Antibody

    Given IV

  • EncorafenibDrug

    Also called Braftovi, LGX 818, LGX-818, LGX818

    Given PO

  • NivolumabBiological

    Also called BMS-936558, MDX-1106, NIVO, ONO-4538

    Given IV

Study groups in NCT04017650
Study groupRoleWhat they receive
Treatment (encorafenib, cetuximab, nivolumab)ExperimentalPatients 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.
Receives: Biological: Cetuximab; Drug: Encorafenib; Biological: Nivolumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Best radiographic response

    Radiographic response will be defined as a complete response or partial response according to immune-related response criteria (Immune-Modified Response Evaluation Criteria in Solid Tumors) and Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria.

    Measured: Within 6 months of initiation of study treatment

  2. Incidence of treatment-related grade 3 adverse events

    Will assess according to Common Terminology Criteria for Adverse Events version 5.0.

    Measured: Up to 28 days

Secondary outcomes (4)

  1. Progression-free survival

    Will be defined according to RECIST 1.1 criteria.

    Measured: Up to 5 years

  2. Overall survival

    Will be defined according to RECIST 1.1 criteria.

    Measured: Up to 5 years

  3. Time to response

    Measured: Up to 5 years

  4. Duration of response

    Measured: Up to 5 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted12 Jul 2019
  2. Study start14 Jun 2019
  3. Primary completion30 Dec 2027 (estimated)
  4. Study completion30 Dec 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
38 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04017650
Sponsor's protocol ID
2018-0993
Other IDs
NCI-2019-04169, 2018-0993
Status last verified
Jun 2026
First submitted
10 Jul 2019
Last updated
11 Jun 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Cetuximab, Encorafenib and Nivolumab in people with BRAF NP_004324.2:p.V600E and Metastatic Colon Adenocarcinoma, run by M.D. Anderson Cancer Center at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 18 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 11 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Best radiographic response (time frame: Within 6 months of initiation of study treatment). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04017650.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Jun 2026.

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