BVD-523 for Uveal Melanoma

Not currently recruiting at 1 trial location

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Dana-Farber Cancer Institute

Must not be taking: CYP inhibitors, CYP inducers

Disqualifiers: Pregnancy, Uncontrolled illness, Recent 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

Compensation: Varies

Number of Visits: 4

Duration: up to 52 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new targeted therapy called BVD-523 for individuals with advanced uveal melanoma, a type of eye cancer that has spread. The goal is to evaluate the effectiveness of BVD-523 in treating this condition. Participants should have measurable stage IV uveal melanoma and must not have received an ERK inhibitor previously. Those who have undergone various treatments for uveal melanoma or exhibit noticeable symptoms might be suitable for the trial. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications, but you cannot participate if you are taking strong inhibitors or inducers of certain liver enzymes (CYP1A2, CYP2D6, and CYP3A4). It's important to discuss your current medications with the study team to ensure there are no interactions.

Is there any evidence suggesting that BVD-523 is likely to be safe for humans?

Research has shown that BVD-523, also known as ulixertinib, was tested for safety in people with advanced eye cancer that has spread. In these studies, patients generally tolerated BVD-523 well. Common side effects included tiredness, nausea, and diarrhea, with most being mild to moderate.

These results come from studies that have already tested BVD-523 in similar patient groups. The later stage of the research provides a substantial amount of safety information. This gives researchers confidence in the treatment's safety for people, although individual experiences may vary. ^{1 2 3 4 5}

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

Unlike the standard treatments for uveal melanoma, which often involve surgery, radiation, or chemotherapy, BVD-523 is unique because it specifically targets a signaling pathway in cancer cells known as the MAPK/ERK pathway. This pathway is often overactive in uveal melanoma, driving tumor growth. By inhibiting this pathway, BVD-523 aims to halt or slow the progression of the disease more effectively. Researchers are excited about this treatment because it offers a targeted approach that could potentially lead to better outcomes with fewer side effects compared to broader treatment options.

What evidence suggests that BVD-523 might be an effective treatment for uveal melanoma?

Research has shown that BVD-523, also known as ulixertinib, targets a specific pathway in the body that aids cell growth and survival. In studies, BVD-523 did not effectively reduce tumor size or halt growth in patients with metastatic uveal melanoma. Despite this, researchers remain interested in its potential due to its targeting of genetic changes commonly found in uveal melanoma. While there is hope for its future use, current evidence does not demonstrate strong effectiveness for this condition. ^{1 2 3 6 7}

Who Is on the Research Team?

Elizabeth Buchbinder, MD

Principal Investigator

Dana-Farber Cancer Institute

Are You a Good Fit for This Trial?

This trial is for adults over 18 with stage IV uveal melanoma that can be measured, who've possibly had treatments before but not with an ERK inhibitor. They should have a life expectancy over 6 months, good organ function and heart health, and must be able to consent. Pregnant women or those on certain drugs affecting liver enzymes are excluded.

Inclusion Criteria

I have at least one tumor that can be measured.

My cancer has spread and can be biopsied.

I agree to use birth control during the study.

Exclusion Criteria

Participants who are receiving any other investigational agents

I haven't had chemotherapy or radiotherapy in the last 4 weeks.

I have not had major surgery within the last 4 weeks.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive BVD-523 at the RP2D of 600mgs taken twice daily orally for 28 consecutive days per cycle

up to 52 weeks

Regular visits for treatment and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

up to 52 weeks

Follow-up visits every 4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• BVD-523

Trial Overview The study tests BVD-523 as a potential treatment for advanced uveal melanoma. It's focused on how well this targeted therapy works in patients who meet specific health criteria and haven't used similar treatments before.

How Is the Trial Designed?

Group I: BVD-523 Experimental Treatment 1 Intervention

BVD-523 is administered at the RP2D of 600mgs taken twice daily orally for 28 consecutive days (1 cycle). Planned does may modified based on toxicity.

Who Is Running the Clinical Trial?

Dana-Farber Cancer Institute

Lead Sponsor

Trials

1,128

Recruited

382,000+

BioMed Valley Discoveries, Inc

Industry Sponsor

Trials

19

Recruited

650+

Published Research Related to This Trial

Current adjuvant therapies for uveal melanoma have not been effective in preventing metastasis, highlighting the need for new treatment strategies.

New approaches are focusing on using genetic criteria to tailor immunotherapy and targeted treatments for patients at risk, with ongoing clinical trials exploring these innovative therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adjuvant Therapy of Uveal Melanoma: Current Status. Triozzi, PL., Singh, AD.[2022]

Citations

1. 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 ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT03417739

A Phase II Study of BVD-523 in Metastatic Uveal Melanoma In this research study, the investigators are evaluating the role of BVD-523 in the treatment of patients with uveal melanoma. Genetic changes within metastatic ...

3. aacrjournals.org aacrjournals.org/cancerrescommun/article/4/5/1321/745436/A-Phase-II-Study-of-ERK-Inhibition-by-Ulixertinib

A Phase II Study of ERK Inhibition by Ulixertinib (BVD-523) in ... We performed a phase II study to determine the efficacy and safety of BVD-523 in patients with metastatic uveal melanoma.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12328531/

State-of-the-art in Metastatic Uveal Melanoma Treatment Despite effective local disease control through radiotherapy and enucleation, approximately 50% of patients develop metastatic disease, predominantly in the ...

5. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/10.1111/pcmr.13161

Emerging therapeutic strategies for metastatic uveal ... This review aims to summarize the emerging targeted and epigenetic therapeutic strategies for metastatic UM carrying specific driver mutations.

6. 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 ... Designed with intent to register, the BVD-523-ABC clinical trial will continue evaluation of ulixertinib in patients with tumors harboring any ...

7. aacrjournals.org aacrjournals.org/cancerrescommun/article-pdf/doi/10.1158/2767-9764.CRC-24-0036/3448399/crc-24-0036.pdf

A Phase II study of ERK inhibition by ulixertinib (BVD-523) in ... Patients and Methods: We performed a phase II study to determine the efficacy and safety of. BVD-523 in patients with metastatic uveal melanoma. This was ...