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Melanoma Stage IIIPhase 2NCT04598009

Binimetinib and Imatinib for Unresectable Stage III-IV KIT-Mutant Melanoma

A Phase 2 study testing Binimetinib and Imatinib in people with Melanoma Stage III and Melanoma Stage IV, run by University of California, San Francisco at 2 sites in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial summary

This phase II trial studies how well binimetinib and imatinib work in treating patients with stage III-IV KIT-mutant melanoma that cannot be removed by surgery (unresectable). Binimetinib and imatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Melanoma Stage III, Melanoma Stage IV
What is being tested?
Binimetinib and Imatinib
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
25 participants
Where
2 sitesUnited States
Study dates
3 Mar 2021to 31 May 2028
Phase
Phase 2
Are there results?
Not yet: the study is under way

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

  • Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%)
  • Have histologically or cytologically confirmed melanoma
  • Have unresectable Stage III or Stage IV melanoma, as per American Joint Committee on Cancer 8th edition guidelines, not amenable to local therapy
  • Have measurable disease by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) criteria
  • Have documentation of KIT-mutant melanoma by Clinical Laboratory Improvement Act (CLIA)-certified testing platform
  • Participants have progressed on prior standard-of-care therapy, or would be ineligible for or unable to tolerate standard-of-care therapy, in the opinion of the treating Investigator
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  • For participants who have received prior ICI, the following is permitted:
  • Prior adjuvant or neoadjuvant ICI, if last dose administered at least 4 weeks prior to study drug start
  • Prior ICI for the treatment of unresectable/metastatic disease, if last dose administered at least 4 weeks prior to study drug start
  • Absolute neutrophil count >= 1,500/microliter (mcL)
  • Platelets >= 100,000/mcL
  • Total bilirubin below normal institutional limits, unless elevated due to Gilbert's syndrome and direct bilirubin is within normal limits
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase (SGOT)) =< 3 x institutional upper limit of normal
  • Alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase (SGPT)) =< 3 x institutional upper limit of normal
  • Creatinine =< 1.5 x within institutional upper limit of normal OR creatinine clearance glomerular filtration rate (GFR) >= 50 mL/min calculated using the Cockcroft-Gault formula
  • Human immunodeficiency virus (HIV)-infected individuals on effective anti-retroviral therapy, with undetectable viral load within 3 months of study drug start, are eligible for this trial
  • For participants with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
  • Individuals with a history of hepatitis C virus (HCV) infection must have been treated and cured. For individuals with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
  • Individuals with new or progressive brain metastases (active brain metastases) or leptomeningeal disease are eligible if the treating physician determines that immediate central nervous system (CNS)-specific treatment is not required prior to study start
  • Individuals with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
  • Imatinib and/or binimetinib may have teratogenic effects. Women of child-bearing potential (WOCBP) must agree to:
  • Use highly effective contraception to avoid pregnancy from screening through 30 days after the last dose of study drugs;
  • Refrain from donating ova during the study through 30 days after the end of systemic exposure to study drugs;
  • Inform her treating physician immediately should she become pregnant or suspect she is pregnant while she is participating in this study
  • Sexually active men enrolled on this protocol must agree to:
  • Use a condom for the duration of study participation and through 90 days after the end of systemic exposure to study drugs;
  • Refrain from donating sperm during the study through 90 days after the end of systemic exposure to study drugs;
  • If the male participant has a partner that is a WOCBP, that partner should also use highly effective contraception for the duration of the study and through 90 days after the end of the male participant's systemic exposure to study drug
  • Inform his treating physician immediately should his partner become pregnant while he is participating in this study
  • Highly effective (i.e., failure rate <1% per year when used consistently and correctly) methods of contraception include:
  • Complete abstinence from heterosexual intercourse
  • Combined (estrogen and progesterone) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal)
  • Progesterone-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable)
  • Intra-uterine device (IUD)
  • Intrauterine hormone-releasing system (IUS)
  • Bilateral tubal occlusion
  • Vasectomized male partner (provided the vasectomized male has received medical assessment of surgical success, and that the male is a female participant's sole sexual partner)
  • Ability to understand a written informed consent document, and the willingness to sign it
  • The participant is deemed by the Investigator to have the initiative and means to be compliant with scheduled visits, treatment plan, and study procedures

Who cannot join

  • Has received systemic anti-cancer therapies within 3 weeks of study drug start, radiation within 2 weeks, antibody therapy within 4 weeks
  • Has not recovered from adverse events due to prior anti-cancer therapy to =< grade 1 or baseline. Note: Stable chronic conditions (grade =< 2) that are not expected to resolve (such as neuropathy, myalgia, alopecia, prior therapy-related endocrinopathies) are exceptions and may enroll
  • Is currently receiving any other investigational agents or has received an investigational agent within 14 days or within 5 half-lives of investigational agent (whichever is shorter), prior to start of study drugs
  • Inability to swallow and retain study drugs
  • Impairment of gastrointestinal function or disease which may significantly alter the absorption of study drugs (e.g., active ulcerative disease, uncontrolled vomiting or diarrhea, malabsorption syndrome, complete small bowel resection), or recent (=< 3 months) history of a partial or complete bowel obstruction, or other conditions that will interfere significantly with the absorption of oral drugs
  • Hypersensitivity to binimetinib or any of its excipients
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  • Hypersensitivity to imatinib or any of its excipients
  • Concurrent neuromuscular disorder that is associated with elevated creatinine-kinase (CK) (e.g., inflammatory myopathies, muscular dystrophy, amyotrophic lateral sclerosis, spinal muscular atrophy)
  • History or current evidence of retinal vein occlusion (RVO) or current risk factors for RVO (e.g., uncontrolled glaucoma or ocular hypertension, history of hyperviscosity of hypercoagulability syndromes); history of retinal degenerative disease
  • Impaired cardiovascular function or clinically significant cardiovascular disease including, but not limited to, any of the following:
  • History of acute coronary syndromes (including myocardial infarction, unstable angina, coronary artery bypass grafting, coronary angioplasty of stenting) < 6 months prior to screening;
  • Congestive heart failure requiring treatment (New York Heart Association grade >= 2);
  • Left ventricular ejection fraction (LVEF) < 50% as determined by multigated acquisition scan (MUGA) or echocardiogram (ECHO);
  • Uncontrolled hypertension defined as persistent systolic blood pressure >= 150 mmHg or diastolic blood pressure >= 100 mmHg despite current therapy;
  • History of presence of clinically significant cardiac arrhythmias (including resting bradycardia, uncontrolled atrial fibrillation or uncontrolled paroxysmal supraventricular tachycardia);
  • Triplicate average baseline corrected QT (QTc) interval >= 480 msec
  • Use of a prohibited medication (including herbal medications, supplements, or foods) that cannot be safely discontinued prior to the start of study treatment
  • Patients on warfarin who cannot be safely transitioned to an alternative systemic anticoagulant
  • History of thromboembolic or cerebrovascular events =< 12 weeks prior to the first dose of study treatment. Examples include transient ischemic attacks, cerebrovascular accidents, hemodynamically significant (i.e. massive or sub-massive) deep vein thrombosis or pulmonary emboli. Note: Patients with either deep vein thrombosis or pulmonary emboli that does not result in hemodynamic instability are allowed to enroll as long as they are on a stable dose of anticoagulants for at least 4 weeks prior to study drug start. Note: Patients with thromboembolic events related to indwelling catheters or other procedures may be enrolled
  • Pregnant women are excluded from this study because binimetinib and imatinib are small molecule inhibitors 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 binimetinib and/or imatinib, breastfeeding should be discontinued prior to study drug start
  • Other severe, acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study treatment administration or that may interfere with the interpretation of study results and, in the judgment of the Investigator, would make the patient an inappropriate candidate for the study

Trial locations and contacts

2 sites in 1 country. Contact the study team or a site near you to ask about taking part.

Sonia Contreras Martinez contact

(415) 514-6427

sonia.contrerasmartinez@ucsf.edu

United States2 sites, 2 recruiting

  • UC San Diego Moores Cancer Center

    La Jolla, California, 92093

    Gregory Daniels, MD, PhD, 858-534-3804, gdaniels@ucsd.edu

    Gregory Daniels, MD, PhD

    Recruiting

  • University of California, San Francisco

    San Francisco, California, 94143

    Sonia Contreras Martinez, 415-514-6427, sonia.sontrerasmartinez@ucsf.edu

    877-827-3222, cancertrials@ucsf.edu

    Recruiting

Other trials in United States

About this study

Official title: A Phase II Study of Binimetinib in Combination With Imatinib in Patients With Advanced KIT-Mutant Melanoma

This phase II trial studies how well binimetinib and imatinib work in treating patients with stage III-IV KIT-mutant melanoma that cannot be removed by surgery (unresectable). Binimetinib and imatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving binimetinib and imatinib may help treat patients with KIT-mutant melanoma.

Read the detailed description

PRIMARY OBJECTIVE:

  1. To evaluate the overall response rate (ORR) of binimetinib plus imatinib in participants with advanced KIT-mutant melanoma.

SECONDARY OBJECTIVES:

  1. To determine the safety and tolerability of binimetinib plus imatinib in participants with advanced KIT-mutant melanoma.

II. To estimate efficacy and survival parameters in participants with advanced KIT-mutant melanoma treated with binimetinib plus imatinib.

III. To estimate efficacy in participants with advanced KIT-mutant melanoma treated with binimetinib plus imatinib.

EXPLORATORY OBJECTIVES:

  1. To investigate association between changes in drug phosphorylated end products (p-KIT, p-MEK, p-ERK) and clinical response.

II. To investigate association between clinical response and baseline Neurofibromatosis 1 (NF1) and SPRED1 status.

III. To investigate pathologic correlates of acquired resistance. IV. To investigate whether NF1 and SPRED1 loss contribute to acquired resistance.

  1. To generate participant-derived xenograft models. VI. To determine the relationship between clinical outcomes and clinicopathologic features including KIT exon mutated, melanoma subtype, melanoma primary site, race/ethnicity, prior treatment history including immune checkpoint inhibitor (ICI)-experienced versus (vs) - naive.

OUTLINE:

Participants receive binimetinib orally (PO) twice daily (BID) on days 1-28 and imatinib PO once daily (QD) on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, participants are followed up at day 30 and 100, and then every 3 months.

Being tested
Binimetinib, Imatinib
Keywords
KIT-Mutant, Unresectable Melanoma, Melanoma
Medical subject headings
Melanoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • BinimetinibDrug

    Also called Binimetinib Oral, Mektovi, ARRY-162, MEK162

    Taken orally (PO) twice a day (BID)

  • ImatinibDrug

    Also called Imatinib Mesylate

    Taken orally (PO) once a day (QD)

Study groups in NCT04598009
Study groupRoleWhat they receive
Treatment (binimetinib, imatinib)ExperimentalPatients receive binimetinib PO BID on days 1-28 and imatinib PO QD on days 1-28. Cycles repeat every 28 days
Receives: Drug: Binimetinib; Drug: Imatinib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Objective response rate (ORR)

    Defined as complete response (CR) or partial response (PR) by Response Evaluation Criteria in Solid Tumors (RECIST v1.1). The ORR at stages 1 and 2 will be estimated using the method of Whitehead, and the p-values for testing the null hypothesis at each stage will use the method of Koyama \& Chen and 90% confidence interval will be reported.

    Measured: Up to week 16

Secondary outcomes (5)

  1. Proportion of participants with treatment-related adverse events (AE)

    Proportion of participants with treatment-related AEs greater than grad2 as graded by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0 will be reported by toxicity.

    Measured: Up to 2 years

  2. Median duration of response

    Will estimate the probability-of-being-in-response function, assuming time to response is exponentially distributed.

    Measured: Up to 2 years

  3. Progression-free survival (PFS)

    Participants with an objective response will be followed for survival from initiation of study treatment until date of disease progression or death from any cause

    Measured: Up to 2 years

  4. Overall survival (OS)

    Participants will be followed from initiation of study treatment until date of disease progression or death from any cause and estimated using the Kaplan-Meier method to estimate the survival rate (95% CI)

    Measured: Up to 2 years

  5. Clinical benefit rate (CBR)

    Defined as CR, PR, or stable disease (SD) >= 16 weeks by RECIST. CBR will be defined as the proportion of participants with CR, PR, or SD for >= 16 weeks.

    Measured: Up to 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted22 Oct 2020
  2. Study start3 Mar 2021
  3. Primary completion31 May 2027 (estimated)
  4. Study completion31 May 2028 (estimated)

Resources

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
25 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04598009
Sponsor's protocol ID
20863
Other IDs
NCI-2020-07748
Status last verified
Aug 2026
First submitted
16 Oct 2020
Last updated
18 Aug 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Binimetinib and Imatinib in people with Melanoma Stage III and Melanoma Stage IV, run by University of California, San Francisco 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 39 inclusion and 21 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: looking for participants now, as of the sponsor's last update on 18 Aug 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?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Sonia Contreras Martinez ((415) 514-6427, sonia.contrerasmartinez@ucsf.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Objective response rate (ORR) (time frame: Up to week 16). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04598009.

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 18 Aug 2026; AzTrials last refreshed its copy on 6 Nov 2026.

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