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

NCT06400225 | Active Not Recruiting Phase 2 FDA Drug

• 3 other identifiers: NCI-2024-01160EAY131-Z1LU10CA180820
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

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

Outcome Measures

Primary Outcomes (1)

• Objective response rate (ORR)

  ORR is defined as the percentage of patients whose tumors have a complete or partial response to treatment among analyzable patients. Objective response is defined consistent with Response Evaluation Criteria in Solid Tumors version 1.1, the Cheson (2014) criteria for lymphoma patients, and the Response Assessment in Neuro-Oncology criteria for glioblastoma patients. 90% two-sided confidence interval is calculated for ORR. For the purposes of this study, patients should be re-evaluated for response: * For treatments given in 21 day (3 week) cycles: every 3 cycles (9 weeks) for the first 33 cycles, and every 4 cycles thereafter (12 weeks) * For treatments given in 28 day (4 week) cycles: every 2 cycles (8 weeks) for the first 26 cycles, and every three cycles thereafter (12 weeks) * For treatments given in 42 day (6 week) cycles: every 2 cycles (12 weeks)

  Up to 3 years

Secondary Outcomes (3)

• Overall survival (OS)

  From start of treatment on that step until death, or censored at the date of last contact, assessed up to 3 years

• 6-month progression free survival (PFS) rate

  From start of treatment on that step until determination of disease progression or death from any cause, censored at the date of last disease assessment for patients who have not progressed, assessed at 6 months

• Progression free survival

  From start of treatment on that step until determination of disease progression or death from any cause, censored at the date of last disease assessment for patients who have not progressed, assessed up to 3 years

Study Arms (1)

Treatment (BVD-523FB [ulixertinib])

EXPERIMENTAL

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.

Procedure: Biopsy Procedure; Procedure: Biospecimen Collection; Procedure: Computed Tomography; Procedure: Echocardiography Test; Procedure: Magnetic Resonance Imaging; Procedure: Radionuclide Imaging; Drug: Ulixertinib

Interventions

Biopsy Procedure PROCEDURE

Undergo biopsy

Also known as: Biopsy, BIOPSY_TYPE, Bx

Treatment (BVD-523FB [ulixertinib])

Biospecimen Collection PROCEDURE

Undergo blood sample collection

Also known as: Biological Sample Collection, Biospecimen Collected, Sample Collection, Specimen Collection

Treatment (BVD-523FB [ulixertinib])

Computed Tomography PROCEDURE

Undergo CT scan

Also known as: 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

Treatment (BVD-523FB [ulixertinib])

Echocardiography Test PROCEDURE

Undergo ECHO

Also known as: EC, Echocardiography

Treatment (BVD-523FB [ulixertinib])

Magnetic Resonance Imaging PROCEDURE

Undergo MRI

Also known as: Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan, Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance, MR, MR Imaging, MRI, MRI Scan, MRIs, NMR Imaging, NMRI, Nuclear Magnetic Resonance Imaging, sMRI, Structural MRI

Treatment (BVD-523FB [ulixertinib])

Radionuclide Imaging PROCEDURE

Undergo nuclear study

Also known as: Gamma Scan, NM, Nuclear Medicine, nuclear medicine scan, radioimaging, Radionuclide Scanning, Scan, Scintigraphy

Treatment (BVD-523FB [ulixertinib])

Ulixertinib DRUG

Given PO

Also known as: BVD-523, VRT752271

Treatment (BVD-523FB [ulixertinib])

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

ECOG-ACRIN Cancer Research Group

Philadelphia, Pennsylvania, 19103, United States

Location

MeSH Terms

Conditions

Lymphoma; Multiple Myeloma

Interventions

Biopsy; Specimen Handling; Magnetic Resonance Spectroscopy; Nuclear Medicine Department, Hospital; ulixertinib

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Neoplasms, Plasma Cell; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemorrhagic Disorders

Intervention Hierarchy (Ancestors)

Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Investigative Techniques; Spectrum Analysis; Chemistry Techniques, Analytical; Hospital Administration; Health Facility Administration; Organization and Administration; Health Services Administration

Study Officials

• Vivek Subbiah

  ECOG-ACRIN Cancer Research Group

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 3, 2024
• First Posted: May 6, 2024
• Study Start: July 24, 2019
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: May 13, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will share

Locations

US (1)