Testing BVD-523FB (Ulixertinib) as Potentially Targeted Treatment in Cancers With Genetic Changes (MATCH - Subprotocol Z1L)

NCT ID: NCT06400225

Last Updated: 2025-11-04

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE2

Total Enrollment

35 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-07-24

Study Completion Date

2026-12-31

Brief Summary

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This phase II MATCH treatment trial tests how well BVD-523FB (ulixertinib) works in treating patients with cancer that has certain genetic changes. BVD-523FB (ulixertinib) is used in patients whose cancer has a mutated (changed) form of a gene called BRAF. It is in a class of medications called kinase inhibitors. It works by blocking the action of proteins that signal cancer cells to multiply. This helps slow or stop the spread of cancer cells.

Detailed Description

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PRIMARY OBJECTIVE:

I. To evaluate the proportion of patients with objective response (OR) to targeted study agent(s) in patients with advanced refractory cancers/lymphomas/multiple myeloma.

SECONDARY OBJECTIVES:

I. To evaluate the proportion of patients alive and progression free at 6 months of treatment with targeted study agent in patients with advanced refractory cancers/lymphomas/multiple myeloma.

II. To evaluate time until death or disease progression. III. To identify potential predictive biomarkers beyond the genomic alteration by which treatment is assigned or resistance mechanisms using additional genomic, ribonucleic acid (RNA), protein and imaging-based assessment platforms.

IV. To assess whether radiomic phenotypes obtained from pre-treatment imaging and changes from pre- through post-therapy imaging can predict objective response and progression free survival and to evaluate the association between pre-treatment radiomic phenotypes and targeted gene mutation patterns of tumor biopsy specimens.

OUTLINE:

Patients receive BVD-523FB (ulixertinib) orally (PO) twice daily (BID) on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo computed tomography (CT) or magnetic resonance imaging (MRI) and blood sample collection throughout the trial. Patients also undergo echocardiography (ECHO) or nuclear study (multigated acquisition \[MUGA\] or similar scan) during screening and on study. Patients may also undergo biopsies on study.

After completion of study treatment, patients are followed every 3 months for 2 years and then every 6 months for 1 year.

Conditions

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Advanced Lymphoma Advanced Malignant Solid Neoplasm Refractory Lymphoma Refractory Malignant Solid Neoplasm Refractory Multiple Myeloma

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Treatment (BVD-523FB [ulixertinib])

Patients receive BVD-523FB (ulixertinib) PO BID on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo CT or MRI and blood sample collection throughout the trial. Patients also undergo ECHO or nuclear study (MUGA or similar scan) during screening and on study. Patients may also undergo biopsies on study.

Group Type EXPERIMENTAL

Biopsy Procedure

Intervention Type PROCEDURE

Undergo biopsy

Biospecimen Collection

Intervention Type PROCEDURE

Undergo blood sample collection

Computed Tomography

Intervention Type PROCEDURE

Undergo CT scan

Echocardiography Test

Intervention Type PROCEDURE

Undergo ECHO

Magnetic Resonance Imaging

Intervention Type PROCEDURE

Undergo MRI

Radionuclide Imaging

Intervention Type PROCEDURE

Undergo nuclear study

Ulixertinib

Intervention Type DRUG

Given PO

Interventions

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Biopsy Procedure

Undergo biopsy

Intervention Type PROCEDURE

Biospecimen Collection

Undergo blood sample collection

Intervention Type PROCEDURE

Computed Tomography

Undergo CT scan

Intervention Type PROCEDURE

Echocardiography Test

Undergo ECHO

Intervention Type PROCEDURE

Magnetic Resonance Imaging

Undergo MRI

Intervention Type PROCEDURE

Radionuclide Imaging

Undergo nuclear study

Intervention Type PROCEDURE

Ulixertinib

Given PO

Intervention Type DRUG

Other Intervention Names

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MR MR Imaging NM Nuclear Medicine nuclear medicine scan radioimaging Radionuclide Scanning Scan Scintigraphy BVD-523 VRT752271 Biopsy BIOPSY_TYPE Bx Biological Sample Collection Biospecimen Collected Specimen Collection CAT CAT Scan Computed Axial Tomography Computerized Axial Tomography Computerized axial tomography (procedure) Computerized Tomography Computerized Tomography (CT) scan CT CT Scan Diagnostic CAT Scan Diagnostic CAT Scan Service Type tomography EC Echocardiography Magnetic Resonance Magnetic Resonance Imaging (MRI) Magnetic resonance imaging (procedure) Magnetic Resonance Imaging Scan Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance MRI MRI Scan MRIs NMR Imaging NMRI Nuclear Magnetic Resonance Imaging sMRI Structural MRI

Eligibility Criteria

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Inclusion Criteria

* Patients must have met applicable eligibility criteria in the Master MATCH Protocol EAY131/ NCI-2015-00054 prior to registration to treatment subprotocol
* Patients must fulfill all eligibility criteria of MATCH Master Protocol at the time of registration to treatment step (Step 1, 3, 5, 7)
* Patients must have a BRAF non-V600 mutation or BRAF fusion, or another BRAF aberration, as determined via the MATCH Master Protocol
* Patients with BRAF V600E/K/R/D mutations are excluded
* Patients must have an electrocardiogram (ECG) within 8 weeks prior to treatment assignment and must have no clinically important abnormalities in rhythm, conduction or morphology of resting ECG (e.g. complete left bundle branch block, third degree heart block)
* Patients must not have known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to BVD-523FB (ulixertinib), dimethyl sulfoxide (DMSO), or excipients
* Patients must not have a left ventricular ejection fraction (LVEF) \< the institutional lower limit of normal (LLN) or \< 50% (whichever is higher)
* Patients must not have prior use of MEK or ERK 1/2 inhibitors
* Patients must not have a history of retinal vein occlusion (RVO) or central serous retinopathy. Patients with visible retinal pathology as assessed by ophthalmologic exam that is considered a risk factor for retinal vein thrombosis or central serous retinopathy will be excluded
* Intraocular pressure is ≤ 21mm Hg as measured by tonography. Patients diagnosed with glaucoma within 1 month prior to Step 1 registration are excluded
* Patients must not have leptomeningeal metastases or spinal cord compression due to disease
* Patients must not have primary malignancy of the central nervous system
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Vivek Subbiah

Role: PRINCIPAL_INVESTIGATOR

ECOG-ACRIN Cancer Research Group

Locations

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ECOG-ACRIN Cancer Research Group

Philadelphia, Pennsylvania, United States

Site Status

Countries

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United States

Other Identifiers

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NCI-2024-01160

Identifier Type: REGISTRY

Identifier Source: secondary_id

EAY131-Z1L

Identifier Type: OTHER

Identifier Source: secondary_id

EAY131-Z1L

Identifier Type: OTHER

Identifier Source: secondary_id

U10CA180820

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NCI-2024-01160

Identifier Type: -

Identifier Source: org_study_id

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