Uveal MelanomaPhase 2NCT03417739
A Phase II Study of BVD-523 in Metastatic Uveal Melanoma
A Phase 2 study testing BVD-523 in people with Uveal Melanoma, run by Dana-Farber Cancer Institute at 2 sites in United States.
Trial summary
This research study is studying a targeted therapy called BVD-523 as a possible treatment for advanced uveal melanoma. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Uveal Melanoma
- What is being tested?
- BVD-523
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 13 participants
- Where
- 2 sitesUnited States
- Study dates
- 26 Mar 2018to 16 Jul 2025
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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.
- Presence of metastatic disease that would be amenable to the required biopsies. Ideally pre and post biopsies should be from the same lesion and otherwise from lesions in the same organ. If not possible, then biopsy of the lesions in different organs will be permitted.
- The effects of BVD-523 on the developing human fetus are unknown. For this reason and because ERK inhibitors could potentially be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and 4 months after completion of BVD-523 administration. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of BVD-523 administration.
- Ability to understand and the willingness to sign a written informed consent document.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Massachusetts General Hospital
Boston, Massachusetts, 02214
Dana Farber Cancer Institute
Boston, Massachusetts, 02215
About this study
This research study is studying a targeted therapy called BVD-523 as a possible treatment for advanced uveal melanoma.
Read the detailed description
This research study is a Phase II clinical trial. Phase II clinical trials test the safety and effectiveness of an investigational drug to learn whether the drug works in treating a specific disease. "Investigational" means that the drug is being studied.
The FDA (the U.S. Food and Drug Administration) has not approved BVD-523 as a treatment for any disease.
BVD-523 has been tested in patients with solid tumors to determine the highest dose of BVD-523 that can be safely given to patients.
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 uveal melanoma activate proteins in the MAPK protein signaling pathway which leads to tumor growth. In the laboratory BVD-523 works against one of these proteins called ERK to decrease tumor growth. In this study, the investigators are testing BVD-523 to see if it works to treat metastatic uveal melanoma.
- Conditions
- Uveal Melanoma
- Being tested
- BVD-523
- Keywords
- Uveal Melanoma
- Medical subject headings
- Uveal Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BVD-523Drug
Also called Ulixertinib
ERK1 and ERK2 inhibitor
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: BVD-523 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: up to 52 weeks
Secondary outcomes (5)
Disease Control Rate
A combination of patients who experience complete response, partial response and stable disease on CT or other form of imaging
Measured: up to 52 weeks
Median Overall Survival
OS based on the Kaplan-Meier method is defined as the time from study entry to death or censored at date last known alive.
Measured: 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
Time from enrollment on study until the tumor is progressing by RECIST v1.0 as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions
Measured: 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
DUSP6 expression was measured using the NanoString nCounter platform. Raw RCC files were processed with the processNanostringData() function, including background correction with negative control probes (p < 0.01) and normalization to positive control probes and housekeeping genes. Resulting data represent background-corrected, normalized counts on a linear scale. Higher DUSP6 expression indicates greater transcript abundance and MAPK pathway feedback activity, while lower expression reflects reduced levels. With ERK inhibition, DUSP6 would be expected to decrease. Change was calculated as the value at pre-treatment minus the value on treatment.
Measured: 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
DNA sequencing will occur in tissue samples from patients treated on study to gain a better understanding of the genetic variability observed in uveal melanoma
Measured: 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.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Jan 2018
- Study start26 Mar 2018
- Primary completion5 May 2020
- Study completion16 Jul 2025
Why it stopped: This was a Simon two stage design trial that terminated after the first stage due to lack of response.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Uveal MelanomaStudies of the same condition, open and under way.
- More trials run by Dana-Farber Cancer InstituteThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 13 participants (actual)
Sponsor and investigators
- Lead sponsor
- Dana-Farber Cancer Institute
- Sponsor type
- University, hospital or other
- Collaborators
- BioMed Valley Discoveries, Inc
- Responsible party
- Principal investigator, F. Stephen Hodi, MD, Dana-Farber Cancer Institute
- Investigators
- F. Stephen Hodi, MD, Principal investigator, Dana-Farber Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03417739
- Sponsor's protocol ID
- 17-526
- Status last verified
- Jul 2026
- First submitted
- 25 Jan 2018
- Last updated
- 27 Jul 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Study of BVD-523 in Metastatic Uveal Melanoma
- ClinicalTrials.gov ID
- NCT03417739
- Acronym / sponsor ID
- 17-526
- Conditions
- Uveal Melanoma
- Keywords
- Uveal Melanoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: This was a Simon two stage design trial that terminated after the first stage due to lack of response.
- Enrolment
- 13 participants (actual)
- Lead sponsor
- Dana-Farber Cancer InstituteUniversity, hospital or other
- Collaborators
- BioMed Valley Discoveries, Inc
- Study start
- 26 Mar 2018 (actual)
- Primary completion
- 5 May 2020 (actual)
- Study completion
- 16 Jul 2025 (actual)
- First posted
- 31 Jan 2018 (actual)
- Results
- Posted 11 Nov 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This research study is studying a targeted therapy called BVD-523 as a possible treatment for advanced uveal melanoma.
Detailed description
This research study is a Phase II clinical trial. Phase II clinical trials test the safety and effectiveness of an investigational drug to learn whether the drug works in treating a specific disease. "Investigational" means that the drug is being studied.
The FDA (the U.S. Food and Drug Administration) has not approved BVD-523 as a treatment for any disease.
BVD-523 has been tested in patients with solid tumors to determine the highest dose of BVD-523 that can be safely given to patients.
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 uveal melanoma activate proteins in the MAPK protein signaling pathway which leads to tumor growth. In the laboratory BVD-523 works against one of these proteins called ERK to decrease tumor growth. In this study, the investigators are testing BVD-523 to see if it works to treat metastatic uveal melanoma.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| BVD-523 | Experimental | Drug: BVD-523BVD-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 may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- 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)
Key exclusion criteria (12 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BVD-523Also: UlixertinibERK1 and ERK2 inhibitor | Drug | BVD-523 |
Primary outcome
Overall Response Rate
Time frame: up to 52 weeks
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.
5 secondary outcomes
Disease Control Rate
Time frame: up to 52 weeks
Median Overall Survival
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Jul 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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HS-IT101 Injection Versus Chemotherapy in the Treatment of Advanced Melanoma（FASTIL-Mela02）
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
F. Stephen Hodi, MD principal investigator
Dana-Farber Cancer Institute
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing BVD-523 in people with Uveal Melanoma, run by Dana-Farber Cancer Institute at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 18 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 27 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 11 Nov 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall Response Rate (time frame: up to 52 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Jul 2026.