Advanced LymphomaPhase 2NCT06400225
Testing BVD-523FB (Ulixertinib) as Potentially Targeted Treatment in Cancers With Genetic Changes (MATCH - Subprotocol Z1L)
A Phase 2 study testing Biopsy Procedure, Biospecimen Collection and Computed Tomography in people with Advanced Lymphoma and Advanced Malignant Solid Neoplasm, run by National Cancer Institute (NCI) at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Advanced Lymphoma, Advanced Malignant Solid Neoplasm, Refractory Lymphoma
- What is being tested?
- Biopsy Procedure, Biospecimen Collection and Computed Tomography
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 35 participants
- Where
- 1 siteUnited States
- Study dates
- 24 Jul 2019to 31 Dec 2026
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
None listed.
Trial locations and contacts
1 site in 1 country.
United States1 site
ECOG-ACRIN Cancer Research Group
Philadelphia, Pennsylvania, 19103
About this study
Official title: MATCH Treatment Subprotocol Z1L: BVD-523FB (Ulixertinib) in Patients With Tumors With BRAF Fusions, or With Non-V600E, Non-V600K BRAF Mutations
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.
Read the detailed description
PRIMARY OBJECTIVE:
- 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:
- 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
- Advanced Lymphoma, Advanced Malignant Solid Neoplasm, Refractory Lymphoma, Refractory Malignant Solid Neoplasm, Refractory Multiple Myeloma
- Being tested
- Biopsy Procedure, Biospecimen Collection, Computed Tomography, Echocardiography Test, Magnetic Resonance Imaging
- Medical subject headings
- Lymphoma, Multiple Myeloma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Biopsy ProcedureProcedure or surgery
Also called Biopsy, BIOPSY_TYPE, Bx
Undergo biopsy
Biospecimen CollectionProcedure or surgery
Also called Biological Sample Collection, Biospecimen Collected, Sample Collection, Specimen Collection
Undergo blood sample collection
Computed TomographyProcedure or surgery
Also called CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography
Undergo CT scan
Echocardiography TestProcedure or surgery
Also called EC, Echocardiography
Undergo ECHO
Magnetic Resonance ImagingProcedure or surgery
Also called Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan
Undergo MRI
Radionuclide ImagingProcedure or surgery
Also called Gamma Scan, NM, Nuclear Medicine, nuclear medicine scan
Undergo nuclear study
UlixertinibDrug
Also called BVD-523, VRT752271
Given PO
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Procedure: Biopsy Procedure; Procedure: Biospecimen Collection; Procedure: Computed Tomography; Procedure: Echocardiography Test; Procedure: Magnetic Resonance Imaging; Procedure: Radionuclide Imaging; Drug: Ulixertinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
Measured: Up to 3 years
Secondary outcomes (3)
Overall survival (OS)
Will be evaluated specifically for each drug (or step). OS will be estimated using the Kaplan-Meier method.
Measured: 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
Progression free survival is defined as time from treatment start date to date of progression or death from any cause, whichever occurs first. Disease progression was evaluated using the 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. Please refer to the protocol for detailed definitions of disease progression. 6 month PFS rate was estimated using the Kaplan-Meier method, which can provide a point estimate for any specific time point.
Measured: 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
PFS was defined as time from treatment start date to date of disease progression or death from any causes, whichever occurred first. Median PFS was estimated using the Kaplan-Meier method. Disease progression was evaluated using the 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. Please refer to the protocol for detailed definitions of disease progression.
Measured: 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
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 May 2024
- Study start24 Jul 2019
- Primary completion15 Oct 2021
- Study completion31 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Advanced LymphomaStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 35 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Vivek Subbiah, Principal investigator, ECOG-ACRIN Cancer Research Group
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06400225
- Sponsor's protocol ID
- NCI-2024-01160
- Other IDs
- NCI-2024-01160, EAY131-Z1L, EAY131-Z1L, U10CA180820
- Status last verified
- May 2026
- First submitted
- 3 May 2024
- Last updated
- 15 Oct 2026
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.