Clinical trial NCT06400225: Testing BVD-523FB (Ulixertinib) as Potentially Targeted Treatment in Cancers With Genetic Changes (MATCH - Subprotocol Z1L)
Official title: MATCH Treatment Subprotocol Z1L: BVD-523FB (Ulixertinib) in Patients With Tumors With BRAF Fusions, or With Non-V600E, Non-V600K BRAF Mutations
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Advanced Lymphoma
Advanced Malignant Solid Neoplasm
Refractory Lymphoma
Refractory Malignant Solid Neoplasm
Refractory Multiple Myeloma
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2024-05-06
Enrollment: 35
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Detailed 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.

Eligibility 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

Primary outcomes:
measure: Objective response rate (ORR)
timeFrame: Up to 3 years
Secondary outcomes:
measure: Overall survival (OS)
timeFrame: From start of treatment on that step until death, or censored at the date of last contact, assessed up to 3 years
measure: 6-month progression free survival (PFS) rate
timeFrame: 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
measure: Progression free survival
timeFrame: 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
Other outcomes:
Locations:
city: Philadelphia
country: United States
facility: ECOG-ACRIN Cancer Research Group
state: Pennsylvania
Study officials:
affiliation: ECOG-ACRIN Cancer Research Group
name: Vivek Subbiah
role: PRINCIPAL_INVESTIGATOR
References: