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

NCT04598009 | Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: 20863NCI-2020-07748
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 2

Brief 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. Giving binimetinib and imatinib may help treat patients with KIT-mutant melanoma.

Conditions

Melanoma Stage III; Melanoma Stage IV

Keywords

KIT-Mutant; Unresectable Melanoma; Melanoma

Outcome Measures

Primary Outcomes (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.

  Up to week 16

Secondary Outcomes (5)

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

  Up to 2 years

• Median duration of response

  Up to 2 years

• Progression-free survival (PFS)

  Up to 2 years

• Overall survival (OS)

  Up to 2 years

• Clinical benefit rate (CBR)

  Up to 2 years

Study Arms (1)

Treatment (binimetinib, imatinib)

EXPERIMENTAL

Patients receive binimetinib PO BID on days 1-28 and imatinib PO QD on days 1-28. Cycles repeat every 28 days

Drug: Binimetinib; Drug: Imatinib

Interventions

Binimetinib DRUG

Taken orally (PO) twice a day (BID)

Also known as: Binimetinib Oral, Mektovi, ARRY-162, MEK162

Treatment (binimetinib, imatinib)

Imatinib DRUG

Taken orally (PO) once a day (QD)

Also known as: Imatinib Mesylate

Treatment (binimetinib, imatinib)

Eligibility Criteria

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

You may qualify if:

• 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
• 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

You may not qualify if:

• 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
• 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);

Sponsors & Collaborators

• University of California, San Francisco: lead
• Array BioPharma: collaborator

Study Sites (2)

UC San Diego Moores Cancer Center

La Jolla, California, 92093, United States

RECRUITING

University of California, San Francisco

San Francisco, California, 94143, United States

RECRUITING

MeSH Terms

Conditions

Melanoma

Interventions

binimetinib; Imatinib Mesylate

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Benzamides; Amides; Organic Chemicals; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidines

Study Officials

• Katy Tsai, MD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Sonia Contreras Martinez

CONTACT

(415) 514-6427; sonia.contrerasmartinez@ucsf.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 16, 2020
• First Posted: October 22, 2020
• Study Start: March 3, 2021
• Primary Completion (Estimated): May 31, 2026
• Study Completion (Estimated): May 31, 2027
• Last Updated: September 3, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)