Open-label Phase 1b Study of Ulixertinib and Cetuximab or Ulixertinib in Combination With Cetuximab and Encorafenib in Patients With Unresectable or Metastatic Colorectal Cancer Who Have Previously Received EGFR or BRAF-directed Therapy

NCT05985954 | Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: 2023-0254NCI-2023-06254
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 1

Brief Summary

To find the recommended dose of ulixertinib that can be given in combination with cetuximab and/or encorafenib to patients with unresectable/metastatic CRC and who have received EGFR or BRAF-directed therapy in the past.

Conditions

Metastatic Colorectal Cancer

Outcome Measures

Primary Outcomes (1)

• Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0

  through study completion; an average of 1 year

Study Arms (2)

BRAF Expansion Cohort

EXPERIMENTAL

1 of these 2 doses will be selected as the recommended dose of ulixertinib that can be given in combination with cetuximab and encorafenib.

Drug: Cetuximab; Drug: Ulixertinib; Drug: Encorafenib

Cohort A

EXPERIMENTAL

1 of these 2 doses will be selected as the recommended dose of ulixertinib that can be given in combination with cetuximab alone.

Drug: Cetuximab; Drug: Ulixertinib

Interventions

Cetuximab DRUG

Given by IV (vein)

Also known as: ERBITUX

BRAF Expansion Cohort; Cohort A

Ulixertinib DRUG

Given by PO

Also known as: BVD-523

BRAF Expansion Cohort; Cohort A

Encorafenib DRUG

Given by PO

BRAF Expansion Cohort

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.
• Non-English speaking patients will be eligible for participation with involvement of the MD Anderson Language Assistance department in the informed consent process (per MD Anderson SOP 04\_Informed Consent Process).
• Individuals lacking the ability, based on reasonable medical judgment, to understand and appreciate the nature and consequences of participation in this study will not be eligible for participation.
• 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.
• Mutation status at the time of colorectal cancer diagnosis performed on tumor tissue or circulating tumor DNA (prior to any systemic chemotherapy):
• Cohort A: KRAS, NRAS, EGFR ectodomain, BRAF V600E wild-type status
• BRAF expansion Cohort: BRAF V600E mutation must be present
• Prior treatment with at least one systemic chemotherapy regimen for mCRC, or recurrence/progression with development of unresectable or metastatic disease within 6 months of adjuvant chemotherapy for resected colorectal cancer.
• Prior treatment with:
• a. Cohort A: anti-EGFR therapy (cetuximab or panitumumab) setting for at least 16 weeks with either CR or PR as best response, prior to progression b. BRAF expansion Cohort: BRAF therapy (not including regorafenib) and anti-EGFR therapy (cetuximab or panitumumab)
• ECOG performance status ≤ 1.
• Patients who received chemotherapy must have recovered (Common Terminology Criteria for Adverse Events \[CTCAE\] Grade ≤1) from the acute effects of chemotherapy except for residual alopecia or Grade 2 peripheral neuropathy prior to day 1 of study. A washout period of at least 21 days is required between last chemotherapy dose and day 1 of study (provided the patient did not receive radiotherapy).
• Patients who received radiotherapy must have completed and fully recovered from the acute effects of radiotherapy. A washout period of at least 7 days is required between end of radiotherapy and day 1 of study.
• Adequate hematologic status: Absolute neutrophil count (ANC) ≥ 1.5 x 109/L; Hemoglobin (Hgb) ≥ 9 g/dL with or without transfusions; Platelets (PLT) ≥ 100 x 109/L without transfusions

You may not qualify if:

• History of grade 3 or 4 allergic reaction or intolerability attributed to cetuximab or panitumumab.
• History of allergic reactions attributed to compounds of chemical or biologic composition similar to those of cetuximab, or if the patient had red meat allergy/tick bite history.
• History of a Grade 3 or 4 allergic reaction or intolerability attributed to encorafenib or other BRAF inhibitor (BRAF Expansion Cohort)
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• Previously exposed to ERK1/2 inhibitor
• Any known 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. Known 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.
• Known leptomeningeal disease
• A history or current evidence/risk of retinal vein occlusion (RVO) or central serous retinopathy (CSR).
• 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) \<12 months prior to screening,
• Symptomatic chronic heart failure (i.e. NYHA class 3 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,
• The patient has a personal history of any of the following conditions: syncope of cardiovascular etiology, ventricular arrhythmia of pathological origin (including, but not limited to, ventricular tachycardia and ventricular fibrillation), or sudden cardiac arrest.
• Uncontrolled hypertension defined as persistent elevation of systolic blood pressure ≥ 170 mmHg or diastolic blood pressure ≥ 100 mm Hg, despite current therapy;

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• BioMed Valley Discoveries, Inc: collaborator
• Eli Lilly and Company: collaborator

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

Related Links

• M D Anderson Cancer Center

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Cetuximab; ulixertinib; encorafenib

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

Intervention Hierarchy (Ancestors)

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

Study Officials

• Christine Parseghian, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Christine Parseghian, MD

CONTACT

(713) 792-2828; GIClinicalTrials@mdanderson.org

Study Design

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

Study Record Dates

• First Submitted: August 3, 2023
• First Posted: August 14, 2023
• Study Start: January 18, 2024
• Primary Completion (Estimated): March 28, 2028
• Study Completion (Estimated): March 28, 2028
• Last Updated: March 12, 2026

Record last verified: 2026-03

Locations

US (1)