Binimetinib for Cancer

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: Corticosteroids, MEK inhibitors

Disqualifiers: Melanoma, CNS lesions, Hepatitis, 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

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

Duration: Up to 3 years

53 Participants Needed

Trial Summary

Do I need to stop my current medications for the trial?

The trial information does not specify if you need to stop taking your current medications. However, it does mention that patients must be off corticosteroid therapy for at least 3 weeks if they have been treated for CNS lesions.

What data supports the effectiveness of the drug Binimetinib for cancer?

Research shows that Binimetinib, a drug that blocks certain proteins (MEK1/2) involved in cancer growth, has been effective in treating specific types of cancer, like melanoma with BRAF and NRAS mutations, and has shown potential in leukemia. It works by stopping cancer cells from growing and dividing, especially when combined with other treatments. ^{1 2 3 4 5}

What safety data exists for Binimetinib (Mektovi) in humans?

Binimetinib has been studied in various clinical trials, showing that it is generally well tolerated in humans. Common mild side effects include rash and nausea, while more serious side effects like retinal issues and pulmonary embolism (a blockage in the lung's blood vessels) have been reported in some cases. ^{1 2 3 6 7}

What makes the drug Binimetinib unique for cancer treatment?

Binimetinib is unique because it is a selective inhibitor of MEK1/2, which are proteins involved in cell growth, and it is particularly effective in treating cancers with specific mutations like BRAF and NRAS. It is taken orally and has shown promise in treating advanced solid tumors and melanoma, especially when used in combination with other therapies. ^{1 2 3 4 5}

What is the purpose of this trial?

This phase II MATCH treatment trial investigates the good and bad effects of binimetinib in patients whose cancer has a genetic change called NRAS mutation. Binimetinib blocks proteins called MEK1 and MEK2, which may be needed for cancer cell growth when an NRAS mutation is present. Researchers hope to learn if binimetinib will shrink this type of cancer or stop its growth.

Research Team

James M Cleary

Principal Investigator

ECOG-ACRIN Cancer Research Group

Eligibility Criteria

This trial is for patients with various cancers, like lymphoma and multiple myeloma, that have a specific NRAS genetic change. Participants need to have good kidney function, normal heart rhythm and ejection fraction, and no severe gastrointestinal issues or active brain lesions. Those with melanoma, previous MEK inhibitor treatments, certain eye diseases or uncontrolled hypertension can't join.

Inclusion Criteria

My recent ECG showed no significant heart issues.

Patients must have met applicable eligibility criteria in the Master MATCH Protocol prior to registration to treatment subprotocol

My kidney function, measured by creatinine levels or clearance, is within the required range.

Exclusion Criteria

I do not have a history of eye diseases that cause vision loss.

I do not have an active hepatitis B or C infection.

My blood pressure is controlled with medication.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive binimetinib orally twice daily on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Up to 3 years

Tumor assessments at baseline, then every 2 cycles for the first 26 cycles and every 3 cycles thereafter

Follow-up

Participants are monitored for safety and effectiveness after treatment completion, with follow-up every 3 months if less than 2 years from study entry, and then every 6 months for year 3.

Up to 3 years

Treatment Details

Interventions

• Binimetinib

Trial Overview The trial is testing Binimetinib's effectiveness on cancers with the NRAS mutation. Binimetinib targets proteins involved in cancer cell growth. The study aims to see if it can shrink these cancers or halt their progression.

Participant Groups

Group I: Treatment (binimetinib) Experimental Treatment 1 Intervention

Patients receive binimetinib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

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?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Findings from Research

In a phase 1 study involving 93 patients with advanced solid tumors, binimetinib was found to have a maximum tolerated dose (MTD) of 60 mg twice daily, but the recommended dose for further studies was adjusted to 45 mg due to ocular toxicity.

Binimetinib showed a manageable safety profile with common side effects including rash and nausea, and demonstrated preliminary anti-tumor activity with three patients with biliary cancer achieving objective responses, indicating potential for further investigation in this group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase 1 dose-escalation and expansion study of binimetinib (MEK162), a potent and selective oral MEK1/2 inhibitor. Bendell, JC., Javle, M., Bekaii-Saab, TS., et al.[2022]

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]

In a study involving 21 Japanese patients with advanced solid tumors, binimetinib was found to have an acceptable safety profile, with the maximum tolerated dose established at 45 mg taken twice daily, despite some patients experiencing reversible retinal adverse events.

While no complete or partial responses were observed, 67% of patients achieved stable disease for over 180 days, indicating that binimetinib can effectively stabilize tumor growth in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I study of binimetinib (MEK162) in Japanese patients with advanced solid tumors. Watanabe, K., Otsu, S., Hirashima, Y., et al.[2022]

In a study involving 28 patients with advanced biliary tract cancer, binimetinib was found to be well tolerated, with common mild side effects like rash (82%) and nausea (54%), and only two patients experienced severe adverse events.

Binimetinib demonstrated promising clinical activity, with 43% of patients achieving stable disease and two patients showing objective responses, including one complete response, suggesting its potential effectiveness in treating this type of cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 1b investigation of the MEK inhibitor binimetinib in patients with advanced or metastatic biliary tract cancer. Finn, RS., Ahn, DH., Javle, MM., et al.[2019]

A 56-year-old woman experienced transient visual symptoms, including blurry vision and colored halos, after starting Encorafenib/Binimetinib for metastatic melanoma, indicating potential retinal side effects of the treatment.

Despite the initial symptoms being linked to subretinal fluid (SRF), the patient later experienced similar visual disturbances without any detectable SRF, suggesting that Binimetinib may cause intermittent visual symptoms even after fluid resolution.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Visual symptoms in a patient treated with MEK inhibitors. Tibaldi, T., Roccuzzo, G., Fazio, A., et al.[2022]

References

1. England pubmed.ncbi.nlm.nih.gov

A phase 1 dose-escalation and expansion study of binimetinib (MEK162), a potent and selective oral MEK1/2 inhibitor. [2022]

2. England pubmed.ncbi.nlm.nih.gov

The discovery and development of binimetinib for the treatment of melanoma. [2021]

3. Germany pubmed.ncbi.nlm.nih.gov

A phase I study of binimetinib (MEK162) in Japanese patients with advanced solid tumors. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

MEK inhibition and immune responses in advanced melanoma. [2021]

5. Japan pubmed.ncbi.nlm.nih.gov

Binimetinib, a novel MEK1/2 inhibitor, exerts anti-leukemic effects under inactive status of PI3Kinase/Akt pathway. [2020]

6. United States pubmed.ncbi.nlm.nih.gov

Phase 1b investigation of the MEK inhibitor binimetinib in patients with advanced or metastatic biliary tract cancer. [2019]

7. United States pubmed.ncbi.nlm.nih.gov

Visual symptoms in a patient treated with MEK inhibitors. [2022]