A Phase II Study of BVD-523 in Metastatic Uveal Melanoma

NCT03417739 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: 17-526
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 2

Brief Summary

This research study is studying a targeted therapy called BVD-523 as a possible treatment for advanced uveal melanoma.

Conditions

Uveal Melanoma

Keywords

Uveal Melanoma

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate

  Overall Response Rate (ORR) was defined as the proportion of participants achieving complete response (CR) or partial response (PR) based on RECIST 1.1 criteria on treatment. Per RECIST 1.1 for target lesions: CR is complete disappearance of all target lesions and PR is at least a 30% decrease in the sum of longest diameter (LD) of target lesions, taking as reference baseline sum LD. PR or better overall response assumes at a minimum incomplete response/stable disease (SD) for the evaluation of non-target lesions and absence of new lesions.

  up to 52 weeks

Secondary Outcomes (5)

• Disease Control Rate

  up to 52 weeks

• Median Overall Survival

  Participant survival information will be collected every 4 weeks from the date of last dose of study drug until the participant's death or until the participant is lost to follow-up, or until study closure. Median follow-up was 6 months.

• Median Time to Tumor Progression

  Between the dates of the start of trial treatment and first documentation of progressive disease. In the absence of documented progressive disease, follow-up will be censored at date of last disease assessment. up to 52 weeks

• Change in Expression Levels of Dual Specificity Phosphatase 6

  Expression levels were compared between pre-treatment and on-treatment (12-16 days) timepoints。

• To Better Understand the Genetic Variability of Uveal Melanoma Through Whole Exome Sequencing

  Tumor biopsies are obtained 7-28 days prior to the first treatment and 12-16 days following the initial treatment in order to facilitate ERK signaling analysis, mutation analysis, sequencing, and cell line development.

Study Arms (1)

BVD-523

EXPERIMENTAL

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.

Drug: BVD-523

Interventions

BVD-523 DRUG

ERK1 and ERK2 inhibitor

Also known as: Ulixertinib

BVD-523

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants must have histologically or cytologically confirmed stage IV uveal melanoma
• Participants must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as ≥20 mm with conventional techniques or as ≥10 mm with spiral CT scan, MRI, or calipers by clinical exam. See Section 11 for the evaluation of measurable disease.
• Patients can have received any number of prior therapies for treatment of their uveal melanoma excluding prior treatment with an ERK inhibitor. Patients who have received prior MEK inhibition or other MAPK targeted agents will be allowed on study.
• Age ≥ 18 years of age.
• ECOG performance status ≤2 (Karnofsky ≥60%, see Appendix A)
• Life expectancy of greater than 6 months
• Participants must have normal organ and marrow function as defined below:
• leukocytes ≥3,000/mcL
• hemoglobin ≥9.0 g/dL
• absolute neutrophil count ≥1,500/mcL
• platelets ≥100,000/mcL
• total bilirubin ≤1.5 × institutional upper limit of normal AST(SGOT)/ALT(SGPT) ≤2.5 × institutional upper limit of normal, unless there is known liver involvement in which case ≤5.0 × institutional upper limit of normal
• creatinine within normal institutional limits OR
• creatinine clearance ≥60 mL/min/1.73 m2 for participants with creatinine levels above institutional normal.
• Participants must have adequate cardiac function, e.g. left ventricular ejection fraction (LVEF) of \>50% as assessed by multi-gated acquisition (MUGA) or ultrasound/echocardiography (ECHO); corrected QT interval (QTc) \<470ms.

You may not qualify if:

• Participants who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C), small molecule targeted therapy (i.e. - kinase inhibitors) within 3 weeks or the last dose of antibody therapy within 4 weeks prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier.
• Participants who are receiving any other investigational agents.
• Major surgery within 4 weeks of the first dose of BVD-523. Tumor embolization procedure or ablation procedure within 2 weeks of first dose of BVD-523.
• Participants with known brain metastases or evidence of leptomeningeal involvement are eligible only if these lesions are treated and both clinically and radiographically stable for at least four weeks. Patients are eligible if they are being treated with a stable dosage of steroids/anticonvulsants, requiring no dose increase for 4 weeks.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to BVD-523.
• Participants receiving any medications or substances that are known to be strong inhibitors of CYP1A2, CYP2D6, and CYP3A4 or strong inducers of CYP3A4 are ineligible. Because the lists of these agents are constantly changing, it is important to regularly consult a frequently-updated list such as http://medicine.iupui.edu/clinpharm/ddis/table.aspx; medical reference texts such as the Physicians' Desk Reference may also provide this information. As part of the enrollment/informed consent procedures, the patient will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the patient is considering a new over-the-counter medicine or herbal product.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Pregnant women are excluded from this study because BVD-523 is an ERK with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with BVD-523 breastfeeding should be discontinued if the mother is treated with BVD-523.
• Gastrointestinal (GI) condition which could impair absorption of study medication or inability to ingest study medication.
• A history of current evidence/risk of retinal vein occlusion (RVO) or central serous retinopathy (CSR)
• Concomitant malignancies or previous malignancies with less than 2 years of disease-free interval at the time of enrollment (except non-melanoma skin cancer, cervical cancer in situ, prostate cancer with undetectable PSA). Other concurrent malignancies must be discussed with the medical monitor prior to enrollment.
• Patients with melanoma of cutaneous, mucosal or acral-lentiginous origin or of unknown primary.

Sponsors & Collaborators

• Dana-Farber Cancer Institute: lead
• BioMed Valley Discoveries, Inc: collaborator

Study Sites (2)

Massachusetts General Hospital

Boston, Massachusetts, 02214, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

MeSH Terms

Conditions

Uveal Melanoma

Interventions

ulixertinib

Condition Hierarchy (Ancestors)

Melanoma; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Uveal Neoplasms; Eye Neoplasms; Neoplasms by Site; Eye Diseases; Uveal Diseases

Results Point of Contact

• Title: Elizabeth Buchbinder, MD
• Organization: Dana Farber Cancer Institute

Elizabeth_buchbinder@dfci.harvard.edu

617-632-5055

Study Officials

• Elizabeth Buchbinder, MD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: January 25, 2018
• First Posted: January 31, 2018
• Study Start: March 26, 2018
• Primary Completion: May 5, 2020
• Study Completion: July 16, 2025
• Last Updated: February 25, 2026
• Results First Posted: November 11, 2021

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)