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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new drug called binimetinib (also known as Mektovi) to determine if it can shrink or halt cancer growth in patients with a specific genetic change called an NRAS mutation. Binimetinib blocks proteins that promote cancer cell growth. The trial seeks participants with this NRAS mutation whose daily lives are affected by cancer, excluding those with melanoma or certain other health conditions. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group of people.

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.

Is there any evidence suggesting that binimetinib is likely to be safe for humans?

Research has shown that patients generally tolerate binimetinib well. In earlier studies, common side effects included nausea, diarrhea, tiredness, and vomiting, affecting 30% or more of participants. While bothersome, these side effects can usually be managed. Binimetinib has also been tested with other drugs, such as encorafenib, and demonstrated a good safety record. Although side effects can occur, they typically aren't severe enough to halt treatment. So far, the safety data for binimetinib appears promising for patients considering this trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Most treatments for cancer focus on killing rapidly dividing cells, but binimetinib works differently by specifically targeting a pathway known as the MAPK/ERK pathway, which is often overactive in certain cancers. This precision approach can potentially lead to fewer side effects compared to traditional chemotherapy. Researchers are excited about binimetinib because it offers a targeted mechanism of action that may slow down or stop tumor growth more effectively and with greater specificity than existing options.

What evidence suggests that binimetinib might be an effective treatment for cancer with an NRAS mutation?

Research has shown that binimetinib can help treat certain types of cancer, particularly those with specific genetic changes. In studies on melanoma, a type of skin cancer, patients using binimetinib with another drug lived about 36.8 months on average, compared to 19.3 months for those not using it. This suggests that binimetinib can extend life in these cases. Additionally, nearly 25% of patients experienced no cancer growth for five years when using binimetinib with another drug. These findings indicate that binimetinib may effectively slow down or shrink cancers with certain mutations. Participants in this trial will receive binimetinib alone to evaluate its effectiveness in treating cancer. ^{2 4 6 7 8}

Who Is on the Research Team?

James M Cleary

Principal Investigator

ECOG-ACRIN Cancer Research Group

Are You a Good Fit for This Trial?

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 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 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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

Citations

1. pfizer.com pfizer.com/news/press-release/press-release-detail/pfizers-braftovir-mektovir-shows-sustained-long-term

Pfizer's BRAFTOVI® + MEKTOVI® Shows Sustained Long- ... BRAFTOVI + MEKTOVI continued to show a substantial median overall survival benefit of 47.6 months in treatment-naïve patients with BRAF ...

2. braftovi.pfizerpro.com braftovi.pfizerpro.com/mektovi-m/overall-survival

Overall survival (OS) In the COLUMBUS trial, cutaneous squamous cell carcinoma (cuSCC), including keratoacanthoma (KA), occurred in 2.6% and basal cell carcinoma occurred in 1.6% of ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S0959804924007299

COLUMBUS 7-year update: A randomized, open-label, ... Median melanoma-specific survival (95 % CI) was 36.8 months (27.7–51.5 months) in the encorafenib plus binimetinib arm and 19.3 months (14.8–25.9 months) in the ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11213720/

A Practical Review of Encorafenib and Binimetinib Therapy ... While the incidence of cutaneous squamous cell carcinoma (SCC) was 12% with dabrafenib monotherapy in a previous trial, SCC was reported in 4% ...

5. braftovimektovi-melanoma.com braftovimektovi-melanoma.com/efficacy

efficacy Almost 1 in 4 patients remained progression free at 5 years with BRAFTOVI + MEKTOVI (23%)3. In the initial analysis (cut-off date May 2016), ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38723373/

COLUMBUS 7-year update: A randomized, open-label ... Results: Seven-year PFS and OS rates (95 % CI) were 21.2 % (14.7-28.4 %) and 27.4 % (21.2-33.9%) in the encorafenib plus binimetinib arm and 6.4 % (2.1-14.0 %) ...

7. jto.org jto.org/article/S1556-0864(25)00753-1/fulltext

Updated Efficacy and Safety From the Phase 2 PHAROS ... The PHAROS primary analysis revealed robust antitumor activity and acceptable safety with encorafenib plus binimetinib in patients with BRAF V600E-mutant ...

8. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40480428/

Updated Efficacy and Safety From the Phase 2 PHAROS ... Conclusions: With longer follow-up, encorafenib plus binimetinib showed durable and clinically meaningful antitumor activity, especially in treatment-naive ...