Ulixertinib for Cancer

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must be taking: Kinase inhibitors

Must not be taking: MEK inhibitors, ERK inhibitors

Disqualifiers: Glaucoma, CNS malignancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 4

Duration: Up to 3 years

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how ulixertinib works for patients with cancer that has specific genetic changes in the BRAF gene. Ulixertinib, a kinase inhibitor, helps slow or stop cancer cell growth. The trial seeks participants whose cancer has a specific BRAF mutation, excluding those with the common BRAF V600 mutations. Participants should not have major heart issues on their ECG or eye problems related to retinal vein conditions. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, it does mention that you must not have used MEK or ERK 1/2 inhibitors before. It's best to discuss your current medications with the trial team.

Is there any evidence suggesting that ulixertinib is likely to be safe for humans?

Research has shown that ulixertinib is generally well tolerated by patients. One study found positive effects in patients with certain advanced solid tumors, suggesting relative safety. However, like any treatment, some side effects were reported, including tiredness, nausea, and diarrhea, which are common with many cancer treatments. Overall, previous patients demonstrated that ulixertinib can be a manageable option. It is important to remember that this treatment is still under study, so new information about its safety may continue to emerge. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Ulixertinib is unique because it targets the ERK pathway, which is a key player in cell growth and survival, making it a promising option for treating cancer. Unlike traditional chemotherapy, which can affect both healthy and cancerous cells, ulixertinib specifically inhibits this pathway, potentially leading to fewer side effects and improved effectiveness. Researchers are excited about ulixertinib because its ability to target specific pathways could result in better outcomes for patients, particularly those who have not responded well to existing treatments.

What evidence suggests that ulixertinib might be an effective treatment for cancer?

Research shows that ulixertinib, a kinase inhibitor, can slow or stop the growth of cancer cells with certain genetic changes by targeting a protein that signals cancer cells to grow. In earlier studies, ulixertinib showed promise in treating cancers with BRAF mutations, a specific genetic change. For instance, it demonstrated varying levels of success, with some positive results in cancers like lung cancer. Reports indicate tumor shrinkage, especially in lab models with BRAF and RAS mutations. While effects vary by cancer type, these findings suggest ulixertinib could benefit patients with certain genetic profiles. Participants in this trial will receive ulixertinib as part of the study treatment. ^{2 3 6 7 8}

Who Is on the Research Team?

Vivek Subbiah

Principal Investigator

ECOG-ACRIN Cancer Research Group

Are You a Good Fit for This Trial?

This trial is for cancer patients with a specific genetic change in the BRAF gene. It's open to those with various cancers, including tumors, lymphoma, and multiple myeloma. Participants must have measurable disease and be able to undergo procedures like echocardiography and biopsies.

Inclusion Criteria

Patients must have met applicable eligibility criteria in the Master MATCH Protocol EAY131/ NCI-2015-00054 prior to registration to treatment subprotocol

My heart's pumping ability is within the normal range.

Patients must fulfill all eligibility criteria of MATCH Master Protocol at the time of registration to treatment step (Step 1, 3, 5, 7)

Exclusion Criteria

My cancer has a BRAF V600 mutation.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive BVD-523FB (ulixertinib) orally twice daily on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Up to 3 years

Regular visits for imaging and blood sample collection

Follow-up

Participants are monitored for safety and effectiveness after treatment completion, with follow-ups every 3 months for 2 years and then every 6 months for 1 year.

3 years

Follow-up visits every 3 months for 2 years, then every 6 months for 1 year

What Are the Treatments Tested in This Trial?

Interventions

• Ulixertinib

Trial Overview The focus of this phase II trial is BVD-523FB (ulixertinib), a kinase inhibitor aimed at treating cancers with mutated BRAF genes. The study will assess how well it stops cancer cells from multiplying by blocking protein signals.

How Is the Trial Designed?

Group I: Treatment (BVD-523FB [ulixertinib]) Experimental Treatment 7 Interventions

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.

Ulixertinib is already approved in United States for the following indications:

Approved in United States as Ulixertinib for:

• None (investigational)

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38683104/

A Phase II Study of ERK Inhibition by Ulixertinib (BVD-523) ... Median time to progression was 2.0 months. There were eight deaths due to disease progression with a median overall survival of 6.9 months. ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2022.40.16_suppl.e15101

Updated clinical outcomes from ULI-EAP-100, an ... Results: As of February 1st, 2022, 48 patients (pts) across 17 sites have been treated with ulixertinib under ULI-EAP-100 including pts with ...

3. aacrjournals.org aacrjournals.org/cancerdiscovery/article/8/2/184/6164/First-in-Class-ERK1-2-Inhibitor-Ulixertinib-BVD

First-in-Class ERK1/2 Inhibitor Ulixertinib (BVD-523) in ... ... results, ranging from melanoma-like outcomes in lung cancer (17) to only rare responses in colorectal cancer (21), and intermediate results in thyroid cancer ( ...

4. asco.org asco.org/abstracts-presentations/ABSTRACT192360

First-in-class oral ERK1/2 inhibitor Ulixertinib (BVD-523) in ... Ulixertinib is an oral ERK1/2 inhibitor that demonstrated potent activity in vitro and tumor regression in BRAF and RAS mutant xenograft models.

5. clinicaltrials.gov clinicaltrials.gov/study/NCT04488003?cond=(CARDIOFACIOCUTANEOUS%20SYNDROME)%20OR%20(MAP2K1)&rank=1

NCT04488003 | Study of Ulixertinib for Patients With ... Early clinical data have demonstrated anti-tumor activity with ulixertinib treatment and have identified specific groups of patients for whom additional ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT01781429

Study Details | NCT01781429 | Phase I Dose-Escalation, ... This open-label, multi-center Phase 1/2 study will assess the safety, pharmacokinetics, and pharmacodynamics of escalating doses of BVD-523 in patients with ...

7. ascopubs.org ascopubs.org/doi/10.1200/JCO.2022.40.16_suppl.TPS3172

A two-part, phase II, multi-center study of the ERK inhibitor ... This multi-center, phase II study, will be conducted in two parts and assess the clinical benefit, safety, pharmacokinetics, and pharmacodynamics of ulixertinib

8. trials.braintumor.org trials.braintumor.org/trials/NCT04566393

Expanded Access to Ulixertinib (BVD-523) in Patients with ... The objective of this expanded access program is to provide ulixertinib (BVD-523) for compassionate use in advanced cancer patients with MAPK pathway-altered ...