Binimetinib + Imatinib for Melanoma

Recruiting at 1 trial location

Overseen By Sonia Contreras Martinez

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of California, San Francisco

Must not be taking: Investigational agents, Warfarin

Disqualifiers: Cardiovascular disease, Gastrointestinal impairment, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 58

Duration: Up to 2 years

25 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines how two drugs, binimetinib (Mektovi) and imatinib, might treat melanoma that cannot be surgically removed. These drugs may block certain enzymes that promote cancer cell growth. The trial targets individuals with advanced melanoma featuring a specific mutation called KIT-mutant, who have not responded to other treatments. Participants must have a diagnosis of unresectable stage III or IV melanoma, with the KIT mutation confirmed by a lab test. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications, but it mentions that you cannot use certain prohibited medications, including some herbal supplements or foods, that cannot be safely discontinued before starting the study treatment. It's best to discuss your current medications with the study team to see if any adjustments are needed.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that using binimetinib and imatinib together is generally safe for patients with KIT-mutant melanoma, a specific type of skin cancer. Studies have found that this treatment's side effects are manageable, even over long periods ranging from about 1.5 months to over 6 years. Importantly, no unexpected side effects have been reported, suggesting that most people should tolerate the treatment well. Researchers are studying this combination for its ability to stop tumor growth by blocking the enzymes cancer cells need to grow. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Binimetinib and Imatinib for melanoma because it targets cancer cells in a unique way. Unlike traditional treatments that mainly focus on the immune system or directly targeting tumors, Binimetinib inhibits the MEK pathway, which is crucial for cell growth and survival, while Imatinib blocks specific proteins that help cancer cells grow. This dual approach can potentially disrupt the cancer's ability to thrive and spread more effectively than single-agent therapies. The combination of these two mechanisms offers a promising new angle in the fight against melanoma.

What evidence suggests that binimetinib and imatinib might be effective for KIT-mutant melanoma?

Research has shown that combining binimetinib and imatinib may help treat KIT-mutant melanoma, a type of skin cancer. In one study, this combination proved effective for 69% of patients with similar advanced tumors. Patients experienced strong and lasting improvements, indicating the treatment's effectiveness and long-lasting benefits. Both drugs block specific proteins that aid cancer cell growth, potentially stopping or slowing tumor growth. This trial will evaluate the effectiveness of this combination treatment for patients with advanced melanoma that cannot be removed by surgery. ^{1 2 3 4 6}

Who Is on the Research Team?

Katy Tsai, MD

Principal Investigator

University of California, San Francisco

Are You a Good Fit for This Trial?

This trial is for adults with unresectable Stage III-IV KIT-mutant melanoma. Participants must have measurable disease progression after standard therapy or be unable to tolerate it, and have good organ function. HIV-positive individuals on effective therapy can join, as well as those with treated/cured hepatitis C or controlled hepatitis B. Pregnant or breastfeeding women cannot participate, and sexually active participants must use contraception.

Inclusion Criteria

My hepatitis B virus load is undetectable with treatment.

You have a detectable tumor according to specific measurement guidelines.

My blood, liver, and kidney functions are all within normal ranges.

Exclusion Criteria

You are allergic to binimetinib or any of its ingredients.

I have or am at risk for blocked veins in my eye.

I have a digestive condition that affects how I absorb medication.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive binimetinib orally twice daily and imatinib once daily in 28-day cycles

Up to 2 years

Monthly visits for each 28-day cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 2 years

Follow-up at day 30 and 100, then every 3 months

What Are the Treatments Tested in This Trial?

Interventions

• Binimetinib
• Imatinib

Trial Overview The study tests binimetinib and imatinib's effectiveness in treating advanced KIT-mutant melanoma by blocking enzymes that promote tumor cell growth. This phase II trial aims to determine if this combination treatment can help manage the disease in patients who cannot undergo surgery.

How Is the Trial Designed?

Group I: Treatment (binimetinib, imatinib) Experimental Treatment 2 Interventions

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

Binimetinib is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as Mektovi for:

• Unresectable or metastatic melanoma with a BRAF V600E or V600K mutation

Approved in European Union as Mektovi for:

• Unresectable or metastatic melanoma with a BRAF V600 mutation

Approved in Canada as Mektovi for:

• Unresectable or metastatic melanoma with a BRAF V600E or V600K mutation

Approved in Japan as Mektovi for:

• Unresectable or metastatic melanoma with a BRAF V600 mutation

Who Is Running the Clinical Trial?

University of California, San Francisco

Lead Sponsor

Trials

2,636

Recruited

19,080,000+

Array BioPharma

Industry Sponsor

Trials

29

Recruited

1,400+

Published Research Related to This Trial

Recent advances in treating metastatic melanoma have been achieved through targeted therapies using BRAF and MEK inhibitors for patients with the BRAF V600 mutation, with combinations like vemurafenib+cobimetinib and dabrafenib+trametinib showing significant efficacy in clinical trials.

Combination therapies have different toxicity profiles compared to single-agent treatments, necessitating new strategies for prevention, detection, and management of adverse events, as outlined in the tolerance data from pivotal trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Management of toxicities of BRAF inhibitors and MEK inhibitors in advanced melanoma]. Sibaud, V., Baric, L., Cantagrel, A., et al.[2021]

Binimetinib, an uncompetitive inhibitor of MEK1/2, has shown significant efficacy in treating metastatic melanoma, particularly in combination with encorafenib, resulting in a progression-free survival (PFS) of 14.9 months compared to 7.3 months with vemurafenib alone in Phase 3 trials.

While binimetinib has a tolerable safety profile, there is currently no long-term data on durable responses or overall survival benefits compared to other treatments, highlighting the need for individualized treatment plans for patients with BRAF-mutated metastatic melanoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The discovery and development of binimetinib for the treatment of melanoma. Tran, B., Cohen, MS.[2021]

A review of 11,721 serious adverse event reports from patients treated with BRAF and MEK inhibitors revealed that different combinations have unique safety profiles, with V+C showing a high incidence of skin toxicities like Stevens-Johnson syndrome.

The combination E+B was notably associated with an increased risk of peripheral neuropathies and renal disorders, as well as a significant rise in reports of Guillain-Barré syndrome, indicating that while these treatments improve survival in melanoma, they also carry serious risks that need careful monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of BRAF+MEK Inhibitor Combinations: Severe Adverse Event Evaluation. Meirson, T., Asher, N., Bomze, D., et al.[2020]

The combination of encorafenib and binimetinib is now the standard treatment for patients with advanced melanoma harboring BRAF V600 mutations, based on the phase III COLUMBUS study.

While this combination therapy is effective, it is associated with specific adverse events such as serious retinopathy and cardiovascular toxicities, highlighting the importance of proactive management to improve treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment experience with encorafenib plus binimetinib for BRAF V600-mutant metastatic melanoma: management insights for clinical practice. Augustyn, K., Joseph, J., Patel, AB., et al.[2023]

In the COLUMBUS trial involving 577 patients with advanced BRAF V600-mutant melanoma, the combination of encorafenib and binimetinib (COMBO450) significantly improved overall survival (OS) to a median of 33.6 months compared to 16.9 months for vemurafenib (VEM), reducing the risk of death by 39%.

The updated analysis also showed that COMBO450 provided a longer progression-free survival (PFS) of 14.9 months compared to 7.3 months for VEM, indicating that this combination therapy offers substantial long-term benefits for patients with this type of melanoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Update on tolerability and overall survival in COLUMBUS: landmark analysis of a randomised phase 3 trial of encorafenib plus binimetinib vs vemurafenib or encorafenib in patients with BRAF V600-mutant melanoma. Ascierto, PA., Dummer, R., Gogas, HJ., et al.[2020]

Encorafenib and binimetinib are effective small-molecule inhibitors that target the BRAF and MEK proteins in the MAPK signaling pathway, significantly improving overall and progression-free survival in patients with metastatic melanoma harboring BRAF V600 mutations.

This combination therapy received FDA approval in June 2018 specifically for treating melanoma with BRAF V600E/K mutations, highlighting its clinical utility and relevance in modern cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Encorafenib and binimetinib for the treatment of BRAF V600E/K-mutated melanoma. Rose, AAN.[2019]

The FDA approved two groundbreaking drugs for malignant melanoma in 2011, marking a significant advancement in treatment after a 13-year gap, specifically ipilimumab for immune checkpoint modulation and targeted therapies like vemurafenib and dabrafenib for BRAF(V600) mutations.

These new therapies have changed the landscape of melanoma treatment, but they also raise important questions about how to best combine and sequence these agents for patients with BRAF mutant melanoma to enhance efficacy and manage resistance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ipilimumab, vemurafenib, dabrafenib, and trametinib: synergistic competitors in the clinical management of BRAF mutant malignant melanoma. Luke, JJ., Hodi, FS.[2021]

The combination of nivolumab and ipilimumab has achieved over 50% 5-year overall survival rates in patients with metastatic melanoma, although this combination is associated with high toxicity.

Current research is exploring new combinations of immune checkpoint inhibitors with other treatments, such as BRAF/MEK inhibitors and oncolytic viruses, aiming to improve long-term survival, especially in patients with poor prognosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Systemic Therapy of Metastatic Melanoma: On the Road to Cure. Steininger, J., Gellrich, FF., Schulz, A., et al.[2021]

Binimetinib is the first targeted therapy that has shown a significant improvement in progression-free survival for patients with NRAS-mutated melanoma, addressing a critical need in this patient population.

This review highlights the potential of binimetinib not only as a standalone treatment but also in combination therapies, which could enhance its effectiveness in managing melanoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A review of binimetinib for the treatment of mutant cutaneous melanoma. Koelblinger, P., Dornbierer, J., Dummer, R.[2023]

The combination of encorafenib (ENC) and binimetinib (BIN) was found to be cost-effective compared to cobimetinib (COB) and vemurafenib (VEM) only at a very high willingness-to-pay threshold of $573,000 per quality-adjusted life year (QALY).

The combination of dabrafenib (DAB) and trametinib (TRA) was determined to be the most optimal treatment option for BRAF-mutated advanced melanoma, dominating the COB + VEM combination in terms of cost-effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Economic Evaluation of Three BRAF + MEK Inhibitors for the Treatment of Advanced Unresectable Melanoma With BRAF Mutation From a US Payer Perspective. Halloush, S., Alkhatib, NS., Almutairi, AR., et al.[2023]

Combination treatments of BRAF and MEK inhibitors, specifically vemurafenib + cobimetinib, dabrafenib + trametinib, and encorafenib + binimetinib, are the standard care for patients with BRAF V600-mutant metastatic melanoma, showing similar clinical efficacy across the board.

Each combination has unique safety profiles, with specific side effects such as fever with dabrafenib + trametinib, photosensitivity with vemurafenib + cobimetinib, and gastrointestinal issues with encorafenib + binimetinib, influencing treatment choices based on patient tolerance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Treatment combinations in BRAF-mutant metastatic melanoma.] Depenni, R.[2022]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.TPS9605

A phase II study of binimetinib plus imatinib in patients with ... This phase II study will be the first to evaluate the efficacy and safety of binimetinib plus imatinib in pts with KIT-mutant melanoma.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04598009

Binimetinib and Imatinib for Unresectable Stage III-IV KIT ... 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 ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8937014/

Phase II Trial of Imatinib Plus Binimetinib in Patients With ... The combination of imatinib and binimetinib is effective in treatment-naive advanced GIST. Deep and durable responses were noted.

4. onclive.com onclive.com/view/imatinib-binimetinib-combo-shows-efficacy-with-manageable-safety-in-treatment-na-ve-advanced-gist

Imatinib/Binimetinib Combo Shows Efficacy With ... The novel combination elicited a best overall response rate (ORR) of 69.0% (2-sided 95% CI, 52.9%-82.4%) among 42 evaluable patients, meeting ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7539481/

The Discovery and Development of Binimetinib for the ... Preclinical and clinical trial data on the drug demonstrate its potent efficacy in cancers, especially melanomas with BRAF and NRAS mutations. Areas Covered:.

6. mycancergenome.org mycancergenome.org/content/clinical_trials/NCT04598009/

Clinical Trial: NCT04598009 - Melanoma Binimetinib and imatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.