Ulixertinib for Cancer

Recruiting at 7 trial locations

Overseen By Rona Yaeger, MD

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: Memorial Sloan Kettering Cancer Center

Must be taking: Chemotherapy, BRAF inhibitors, MEK inhibitors

Must not be taking: CYP inhibitors, P-glycoprotein inhibitors

Disqualifiers: Uncontrolled conditions, Major surgery, 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: Unknown

Duration: 12 months

38 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test whether ulixertinib (also known as BVD-523) is safe and effective for treating histiocytic neoplasms, a group of rare cancers. Researchers seek to understand how this treatment works, particularly in individuals with specific gene changes in the MAPK pathway, which can influence cancer growth. Participants will receive ulixertinib in 28-day cycles to assess its impact. The trial suits those with a histiocytic neoplasm that hasn't responded well to other treatments or if the disease is causing significant health issues. As a Phase 2 trial, the research focuses on evaluating the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial requires that you stop taking any histiocytic neoplasm-directed therapy (like chemotherapy or targeted therapy) at least 28 days before starting ulixertinib. Also, you cannot take certain medications that affect specific liver enzymes (CYP1A2, CYP2D6, CYP3A4) or p-glycoprotein inhibitors during the trial.

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

Research has shown that ulixertinib is generally safe. In studies where patients took 600 mg twice daily, the treatment was well-tolerated and showed positive effects for some cancers, such as melanoma. Ulixertinib's safety profile resembles that of MEK inhibitors, another cancer treatment, suggesting patients might experience similar, manageable side effects. Reports suggest ulixertinib holds promise for cancers with specific genetic changes. Overall, early findings indicate that ulixertinib's safety aligns with expectations for this type of treatment. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for cancer?

Ulixertinib is unique because it targets the mitogen-activated protein kinase (MAPK) pathway, which plays a crucial role in cell division and survival. Many existing cancer treatments don't specifically target this pathway, which is known to be altered in various cancers. By directly inhibiting the MAPK pathway, ulixertinib offers a novel approach that could potentially improve outcomes for patients with these specific genetic mutations. Researchers are excited because this targeted mechanism may provide a more effective treatment option with potentially fewer side effects compared to traditional chemotherapy.

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

Research shows that ulixertinib, a type of drug, may help treat cancers by targeting the MAPK pathway in cells, which often contributes to cancer growth. Studies have found that ulixertinib can block this pathway and reduce cancer cell survival at doses patients can safely receive. The drug has shown promise in patients with certain genetic changes in the MAPK pathway, suggesting it might work for cancers related to these changes. In this trial, participants will receive ulixertinib, regardless of whether they have a MAPK pathway mutation. However, it did not prove effective for patients with metastatic uveal melanoma, a type of eye cancer. Overall, early evidence suggests ulixertinib could be helpful for cancers with MAPK pathway mutations. ^{2 3 6 7 8}

Who Is on the Research Team?

Eli Diamond, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

Adults with histiocytic neoplasms, a type of tumor, can join this trial. They must have tried other treatments without success or be unlikely to benefit from conventional therapies. Participants need proper liver and kidney function, no severe infections or medical conditions, and cannot be pregnant. A mutation in certain genes is required.

Inclusion Criteria

My liver functions are within the required range.

I am at least 18 years old, or at least 12 years old after certain safety checks.

My diagnosis of a histiocytic disorder is confirmed by lab tests and imaging.

Exclusion Criteria

I do not have any serious active infections.

I am not taking drugs that affect liver enzymes.

I do not have any severe or uncontrolled health conditions.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive ulixertinib, starting at 300 mg twice daily, for every 28-day cycle

12 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Ulixertinib

Trial Overview The study tests ulixertinib's effectiveness and safety for treating histiocytic neoplasms. It involves people who've had prior treatments but still show disease progression or intolerance to those treatments.

How Is the Trial Designed?

Group I: No Mitogen-activated protein kinase (MAPK) pathway mutation identified (exploratory cohort) Experimental Treatment 1 Intervention

Patients in this study will receive ulixertinib, starting at 300 mg twice daily, for every 28-day cycle.

Group II: Mitogen-activated protein kinase (MAPK) pathway mutation (primary cohort) Experimental Treatment 1 Intervention

Patients in this study will receive ulixertinib, starting at 300 mg twice daily, for every 28-day cycle.

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?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

BioMed Valley Discoveries, Inc

Industry Sponsor

Trials

19

Recruited

650+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10013652/

The first-in-class ERK inhibitor ulixertinib shows promising ... Results. Ulixertinib inhibited MAPK pathway activity in both models, and reduced cell viability in BT40 with clinically achievable concentrations in the low ...

2. 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 ... Based on the preclinical data, it was expected that ulixertinib would have activity in patients with melanoma harboring mutations in the MAPK pathway (39).

3. 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 ...

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

A Phase II Study of ERK Inhibition by Ulixertinib (BVD-523) ... Conclusions: ERK inhibition with ulixertinib (BVD-523) did not demonstrate activity in patients with metastatic uveal melanoma. The toxicities ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT04566393

NCT04566393 | Expanded Access to Ulixertinib (BVD-523) ... The objective of this expanded access program is to provide ulixertinib (BVD-523) for compassionate use in advanced cancer patients with MAPK pathway-altered ...

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

First-in-class oral ERK1/2 inhibitor Ulixertinib (BVD-523) in ... Conclusions: Ulixertinib at 600 mg twice a day has an acceptable safety profile and has produced durable responses in pts with NRAS mutant melanoma, BRAF ...

7. 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 ...

8. 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