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

National Cancer Institute (NCI)

Status and phase: Active, not recruiting; Phase 2

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

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

Study type: Interventional

Funder types: NIH

Identifiers

NCT06400225

NCI-2024-01160 (Registry Identifier)

U10CA180820 (U.S. NIH Grant/Contract)

EAY131-Z1L (Other Identifier)

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 35 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion criteria

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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35 participants in 1 patient group

Treatment (BVD-523FB [ulixertinib])

Experimental group

Description:

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.

Treatment:

Procedure: Magnetic Resonance Imaging

Procedure: Radionuclide Imaging

Procedure: Echocardiography Test

Procedure: Biospecimen Collection

Drug: Ulixertinib

Procedure: Computed Tomography

Procedure: Biopsy Procedure