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

NCT04017650 | Active Not Recruiting Phase 1 FDA Drug

• 2 other identifiers: 2018-0993NCI-2019-04169
• Study Type: interventional
• Target: 38
• Locations: 1 country
• Sites: 1

Brief 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 (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.

Conditions

Stage IIIA Colorectal Cancer AJCC v8; Unresectable Colon Adenocarcinoma; BRAF NP_004324.2:p.V600E; Metastatic Colon Adenocarcinoma; Progressive Disease; Recurrent Colorectal Carcinoma; Metastatic Microsatellite Stable Colorectal Carcinoma; Stage IIIB Colorectal Cancer AJCC v8; Stage IIIC Colorectal Cancer AJCC v8; Metastatic Rectal Adenocarcinoma; Stage III Colorectal Cancer AJCC v8; Stage IV Colorectal Cancer AJCC v8; Stage IVA Colorectal Cancer AJCC v8; Stage IVB Colorectal Cancer AJCC v8; Stage IVC Colorectal Cancer AJCC v8; Unresectable Rectal Adenocarcinoma

Outcome Measures

Primary Outcomes (2)

• 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.

  Within 6 months of initiation of study treatment

• Incidence of treatment-related grade 3 adverse events

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

  Up to 28 days

Secondary Outcomes (4)

• Progression-free survival

  Up to 5 years

• Overall survival

  Up to 5 years

• Time to response

  Up to 5 years

• Duration of response

  Up to 5 years

Study Arms (1)

Treatment (encorafenib, cetuximab, nivolumab)

EXPERIMENTAL

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.

Biological: Cetuximab; Drug: Encorafenib; Biological: Nivolumab

Interventions

Cetuximab BIOLOGICAL

Given IV

Also known as: Cetuximab Biosimilar CDP-1, Cetuximab Biosimilar CMAB009, Cetuximab Biosimilar KL 140, Chimeric Anti-EGFR Monoclonal Antibody, Chimeric MoAb C225, Chimeric Monoclonal Antibody C225, Erbitux, IMC-C225

Treatment (encorafenib, cetuximab, nivolumab)

Encorafenib DRUG

Given PO

Also known as: Braftovi, LGX 818, LGX-818, LGX818

Treatment (encorafenib, cetuximab, nivolumab)

Nivolumab BIOLOGICAL

Given IV

Also known as: BMS-936558, MDX-1106, NIVO, ONO-4538, Opdivo

Treatment (encorafenib, cetuximab, nivolumab)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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;

You may not qualify if:

• 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.
• 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:

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• MD Anderson Cancer Center

MeSH Terms

Conditions

Colonic Neoplasms; Rectal Neoplasms; Disease Progression; Colorectal Neoplasms

Interventions

Cetuximab; encorafenib; Nivolumab

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Van K Morris

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 10, 2019
• First Posted: July 12, 2019
• Study Start: June 14, 2019
• Primary Completion (Estimated): December 30, 2027
• Study Completion (Estimated): December 30, 2027
• Last Updated: June 11, 2026

Record last verified: 2026-06

Locations

US (1)