NCT03417739

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

Terminated Phase 2 Results posted Last updated 25 February 2026

What this trial tests

Phase 2 trial testing BVD-523 in Uveal Melanoma in 13 participants. Terminated before completion.

Timeline

26 March 2018

Primary endpoint
5 May 2020

16 July 2025

Quick facts

Lead sponsor	Dana-Farber Cancer Institute
Phase	Phase 2
Status	Terminated
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	treatment
Enrollment	13
Start date	26 March 2018
Primary completion	5 May 2020
Estimated completion	16 July 2025
Sites	2 locations across United States

Drugs / interventions tested

• BVD-523 — full drug profile →

Conditions studied

• Uveal Melanoma — all drugs for Uveal Melanoma →

Sponsor

Dana-Farber Cancer Institute

Who can join

18 and older, any sex, with Uveal Melanoma. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Overall Response Rate Primary · 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.

Group	Value	95% CI
BVD-523	0	0 – 20.5

Disease Control Rate Secondary · up to 52 weeks

A combination of patients who experience complete response, partial response and stable disease on CT or other form of imaging

Group	Value	95% CI
BVD-523	0

Median Overall Survival Secondary · 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.

OS based on the Kaplan-Meier method is defined as the time from study entry to death or censored at date last known alive.

Group	Value	95% CI
BVD-523	6.9	3.2 – 8.3

Median Time to Tumor Progression Secondary · 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

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

Group	Value	95% CI
BVD-523	2	1.8 – 3.6

Change in Expression Levels of Dual Specificity Phosphatase 6 Secondary · Expression levels were compared between pre-treatment and on-treatment (12-16 days) timepoints。

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 th

Group	Value	95% CI
BVD-523	311.08	-32.73 – 2514.83

To Better Understand the Genetic Variability of Uveal Melanoma Through Whole Exome Sequencing Secondary · 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.

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

Group	Value	95% CI
BVD-523	0

Adverse events — posted to ClinicalTrials.gov

Time frame: AE data collected at day 1 of each cycle, and day 15 of cycle 1, days 22 to 28 of cycle 2. Also during off treatment follow-up. AE 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 up to one year.. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

BVD-523

Serious: 5/13 (38%)

Deaths: 0/13

Serious adverse events (7 terms)

Reaction	System	BVD-523
Alanine aminotransferase increased	Investigations	—
Aspartate aminotransferase increased	Investigations	—
Anemia	Blood and lymphatic system disorders	—
Serum amylase increased	Investigations	—
Hyponatremia	Metabolism and nutrition disorders	—
Pruritus	Skin and subcutaneous tissue disorders	—
Rash maculo-papular	Skin and subcutaneous tissue disorders	—

Other adverse events (76 terms — click to expand)

Reaction	System	BVD-523
Diarrhea	Gastrointestinal disorders	—
Nausea	Gastrointestinal disorders	—
Fatigue	General disorders and administration site conditions	—
Anorexia	Metabolism and nutrition disorders	—
Rash acneiform	Skin and subcutaneous tissue disorders	—
Abdominal pain	Gastrointestinal disorders	—
Pruritus	Skin and subcutaneous tissue disorders	—
Edema limbs	General disorders and administration site conditions	—
Hypoalbuminemia	Metabolism and nutrition disorders	—
Rash maculo-papular	Skin and subcutaneous tissue disorders	—
Constipation	Gastrointestinal disorders	—
Gastrointestinal disorders - Other, specify	Gastrointestinal disorders	—
Fever	General disorders and administration site conditions	—
General disorders and administration site conditions - Other, specify	General disorders and administration site conditions	—
Creatinine increased	Investigations	—
Dehydration	Metabolism and nutrition disorders	—
Dizziness	Nervous system disorders	—
Hematuria	Renal and urinary disorders	—
Cough	Respiratory, thoracic and mediastinal disorders	—
Dyspnea	Respiratory, thoracic and mediastinal disorders	—
Skin and subcutaneous tissue disorders - Other, specify	Skin and subcutaneous tissue disorders	—
Eye disorders - Other, specify	Eye disorders	—
Vomiting	Gastrointestinal disorders	—
Fracture	Injury, poisoning and procedural complications	—
Alanine aminotransferase increased	Investigations	—
Aspartate aminotransferase increased	Investigations	—
Hyponatremia	Metabolism and nutrition disorders	—
Anxiety	Psychiatric disorders	—
Alopecia	Skin and subcutaneous tissue disorders	—
Hypotension	Vascular disorders	—
Anemia	Blood and lymphatic system disorders	—
Blood and lymphatic system disorders - Other, specify	Blood and lymphatic system disorders	—
Lymph node pain	Blood and lymphatic system disorders	—
Palpitations	Cardiac disorders	—
Supraventricular tachycardia	Cardiac disorders	—
Blurred vision	Eye disorders	—
Abdominal distension	Gastrointestinal disorders	—
Anal ulcer	Gastrointestinal disorders	—
Ascites	Gastrointestinal disorders	—
Esophageal stenosis	Gastrointestinal disorders	—

Most-reported serious reactions: Alanine aminotransferase increased, Aspartate aminotransferase increased, Anemia, Serum amylase increased, Hyponatremia, Pruritus, Rash maculo-papular.

Data from ClinicalTrials.gov NCT03417739 adverse events section.

Sponsor's own description

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

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Targeting the ERK Signaling Pathway in Melanoma.
   Savoia P, Fava P, Casoni F, Cremona O. · · 2019 · cited 137× · PMID 30934534 · DOI 10.3390/ijms20061483
2. Progress on Ras/MAPK Signaling Research and Targeting in Blood and Solid Cancers.
   Dillon M, Lopez A, Lin E, Sales D, et al · · 2021 · cited 99× · PMID 34680208 · DOI 10.3390/cancers13205059
3. Oncogenic KRAS blockade therapy: renewed enthusiasm and persistent challenges.
   Tang D, Kroemer G, Kang R. · · 2021 · cited 65× · PMID 34607583 · DOI 10.1186/s12943-021-01422-7
4. Update on uveal melanoma: Translational research from biology to clinical practice (Review).
   Ortega MA, Fraile-Martínez O, García-Honduvilla N, Coca S, et al · · 2020 · cited 47× · PMID 33173970 · DOI 10.3892/ijo.2020.5140
5. Molecular Insights and Emerging Strategies for Treatment of Metastatic Uveal Melanoma.
   Mallone F, Sacchetti M, Lambiase A, Moramarco A. · · 2020 · cited 34× · PMID 32992823 · DOI 10.3390/cancers12102761
6. Emerging strategies to treat rare and intractable subtypes of melanoma.
   Alicea GM, Rebecca VW. · · 2021 · cited 30× · PMID 32274887 · DOI 10.1111/pcmr.12880
7. Targeting ERK beyond the boundaries of the kinase active site in melanoma.
   Sammons RM, Ghose R, Tsai KY, Dalby KN. · · 2019 · cited 29× · PMID 31190430 · DOI 10.1002/mc.23047
8. Genetic Landscape and Emerging Therapies in Uveal Melanoma.
   Seedor RS, Orloff M, Sato T. · · 2021 · cited 27× · PMID 34771666 · DOI 10.3390/cancers13215503