Encorafenib + Binimetinib for Non-Small Cell Lung Cancer

No longer recruiting at 215 trial locations

Overseen By Pfizer Pfizer CT.gov Call Center

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Pfizer

Must not be taking: BRAF inhibitors, MEK inhibitors

Disqualifiers: EGFR mutation, ALK fusion, ROS1 rearrangement, 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: 32

Duration: Up to 36 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of two drugs, encorafenib (Braftovi) and binimetinib (Mektovi), to determine their safety and effectiveness for individuals with a specific type of advanced lung cancer called non-small cell lung cancer (NSCLC) that has a BRAFV600E mutation. The goal is to assess whether these drugs can help when the cancer is in a late stage with specific genetic changes. The study seeks participants with stage IV NSCLC with the BRAFV600E mutation who have either not started treatment or have undergone one round of certain treatments. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, if you have previously been treated with BRAF or MEK inhibitors, you would not be eligible for this trial.

Is there any evidence suggesting that the combination of encorafenib and binimetinib is likely to be safe for humans?

Research shows that using encorafenib and binimetinib together is generally safe for treating certain cancers. In past studies, this combination was given to patients with a specific change called the BRAF V600E mutation. Many of these patients saw their tumors shrink, with about 75% of those untreated before experiencing tumor reduction.

Safety information from these studies suggests that most people can handle this treatment well. While side effects can occur, they were usually manageable. This conclusion comes from earlier research where the treatment was tested over a longer period.

These results offer reassurance about the safety of encorafenib and binimetinib for those considering joining a clinical trial. However, individual experiences may differ, so discussing possible side effects with a healthcare provider is always advisable. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for non-small cell lung cancer?

Researchers are excited about the combination of encorafenib and binimetinib for non-small cell lung cancer because these treatments target specific genetic mutations in cancer cells. Unlike standard chemotherapy, which attacks rapidly dividing cells indiscriminately, encorafenib and binimetinib specifically inhibit proteins in the MAPK pathway, which is often overactive in cancer cells. This targeted approach can potentially lead to more effective treatment with fewer side effects. Furthermore, these drugs are taken orally, providing a more convenient and less invasive option compared to traditional intravenous treatments.

What evidence suggests that encorafenib and binimetinib could be effective for non-small cell lung cancer?

Research shows that using encorafenib and binimetinib together has promising effects for treating certain types of cancer. In patients with BRAF V600E-mutant metastatic non-small cell lung cancer (NSCLC), studies have shown that this combination can significantly reduce tumor size. Specifically, 75% of patients who had never received treatment before saw their tumors shrink. These patients also experienced a significant increase in survival time, living a median of 47.6 months longer. This trial will evaluate the effects of encorafenib and binimetinib together, suggesting they may provide lasting and meaningful benefits, especially for those who haven't tried other treatments yet. ^{1 2 3 4 6}

Who Is on the Research Team?

Pfizer CT.gov Call Center

Principal Investigator

Pfizer

Are You a Good Fit for This Trial?

This trial is for adults with advanced Stage IV non-small cell lung cancer (NSCLC) that has a specific mutation called BRAFV600E. It's open to those who haven't had treatment or have only had one prior line of platinum-based chemo or anti-PD-1/PD-L1 therapy. Participants need to be relatively healthy, able to perform daily activities with ease (ECOG 0-1), and have normal organ function.

Inclusion Criteria

You have a tumor that can be measured using specific guidelines for evaluating cancer.

My blood tests show normal white blood cells, platelets, and hemoglobin levels.

Your total bilirubin levels in the blood are not more than 1.5 times the upper limit of normal.

Exclusion Criteria

I have not taken BRAF or MEK inhibitors before.

I have not had a stroke or blood clot in the last 3 months.

I have brain metastasis or other active brain-related cancer issues.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive encorafenib and binimetinib orally in 28-day cycles

Up to 36 months

Cycle 1 Day 1, Cycle 2 Day 1 ±3 Days, Day 1 ±3 Days in Subsequent Cycles

Follow-up

Participants are monitored for safety and effectiveness after treatment

30 days

Safety follow-up visit (30 days [±7 days] after the EOT visit)

Open-label extension (optional)

Participants may opt into continuation of treatment long-term

Long-term

What Are the Treatments Tested in This Trial?

Interventions

• Binimetinib
• Encorafenib

Trial Overview The study tests the combination of two drugs, encorafenib and binimetinib, in patients with a certain type of lung cancer mutation. It aims to see how safe this combo is and how well it works either as an initial treatment or after first-line therapy.

How Is the Trial Designed?

Group I: Treatment Period Experimental Treatment 2 Interventions

Study treatment with encorafenib and binimetinib will be self-administered orally without regard to food. Patients will receive the following per 28-day (± 3 days) cycle: * Encorafenib: 450 mg (6 × 75 mg capsule) once daily (QD) * Binimetinib: 45 mg (3 × 15 mg tablet) twice daily (BID)

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?

Pfizer

Lead Sponsor

Trials

4,712

Recruited

50,980,000+

Known For

Vaccine Innovations

Top Products

Viagra, Zoloft, Lipitor, Prevnar 13

Albert Bourla

Pfizer

Chief Executive Officer since 2019

PhD in Biotechnology of Reproduction, Aristotle University of Thessaloniki

Patrizia Cavazzoni

Pfizer

Chief Medical Officer

MD from McGill University

Published Research Related to This Trial

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]

Encorafenib and binimetinib, a combination of a BRAF inhibitor and a MEK inhibitor, received FDA approval in June 2018 for treating patients with unresectable or metastatic melanoma that has specific BRAF mutations (V600E or V600K).

The combination therapy is also being explored in ongoing phase III clinical trials for metastatic colorectal cancer, indicating its potential broader application beyond melanoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Encorafenib and Binimetinib: First Global Approvals. Shirley, M.[2019]

In a phase II study involving 98 patients with BRAFV600E-mutant metastatic non-small-cell lung cancer (NSCLC), the combination of encorafenib and binimetinib achieved a confirmed objective response rate of 75% in treatment-naïve patients and 46% in previously treated patients, indicating significant efficacy.

The treatment was generally well-tolerated, with common side effects including nausea (50%) and diarrhea (43%), but it also led to dose reductions in 24% of patients and one serious adverse event of intracranial hemorrhage, highlighting the importance of monitoring safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II, Open-Label Study of Encorafenib Plus Binimetinib in Patients With BRAFV600-Mutant Metastatic Non-Small-Cell Lung Cancer. Riely, GJ., Smit, EF., Ahn, MJ., et al.[2023]

The combination of encorafenib and binimetinib was found to be safe and showed promising activity in patients with BRAF V600E-mutant solid tumors, with a recommended phase 2 dose established for further studies.

In phase II, the treatment resulted in confirmed responses in 67% of BRAFi-naïve melanoma patients, indicating significant efficacy, while the most common serious side effect was increased alanine aminotransferase levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase Ib/II Study of the BRAF Inhibitor Encorafenib Plus the MEK Inhibitor Binimetinib in Patients with BRAFV600E/K -mutant Solid Tumors. Sullivan, RJ., Weber, J., Patel, S., et al.[2021]

The combination of encorafenib and binimetinib for treating BRAF-mutant advanced melanoma shows similar efficacy to existing treatments like dabrafenib+trametinib and vemurafenib+cobimetinib, based on clinical trial results.

This new combination has a lower incidence of certain side effects, such as pyrexia and photosensitivity, which can significantly improve the quality of life for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Long-term efficacy of encorafenib plus binimetinib combined treatment: case report.] Spagnolo, F.[2021]

In a study of melanoma patients treated with encorafenib and binimetinib, the most common skin-related side effects were palmoplantar hyperkeratosis (54%) and palmoplantar erythrodysesthesia (58%) when using encorafenib alone.

Encouragingly, the combination therapy of encorafenib and binimetinib was found to be well tolerated, with fewer cutaneous adverse events compared to established BRAF inhibitors, suggesting a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The spectrum of cutaneous adverse events during encorafenib and binimetinib treatment in B-rapidly accelerated fibrosarcoma-mutated advanced melanoma. Graf, NP., Koelblinger, P., Galliker, N., et al.[2019]

In the COLUMBUS study involving 577 patients with advanced BRAF-mutant melanoma, the combination treatment of encorafenib plus binimetinib significantly improved health-related quality of life (HRQoL) scores compared to vemurafenib, indicating a meaningful enhancement in patients' perceived health status.

Patients receiving the combination therapy also experienced a delay in deterioration of quality of life, suggesting that this treatment not only improves survival but also helps maintain a better quality of life during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Quality of life in patients with BRAF-mutant melanoma receiving the combination encorafenib plus binimetinib: Results from a multicentre, open-label, randomised, phase III study (COLUMBUS). Gogas, H., Dummer, R., Ascierto, PA., et al.[2021]

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]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO-25-02023

Updated Overall Survival Analysis From the Phase 2 ... The phase 2 PHAROS study previously showed that encorafenib plus binimetinib has antitumor activity in patients with BRAF V600E-mutant ...

2. 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 ...

3. onclive.com onclive.com/view/updated-overall-survival-analysis-from-the-phase-2-pharos-study-of-encorafenib-plus-binimetinib-in-patients-with-braf-v600e-mutant-metastatic-nsclc-mnsclc-

Updated overall survival analysis from the phase 2 ... An expert discusses updated overall survival results from the phase 2 PHAROS study evaluating encorafenib plus binimetinib in patients with BRAF ...

4. 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 ...

5. braftovi.com braftovi.com/n

BRAFTOVI® (encorafenib) + MEKTOVI® (binimetinib) In a clinical trial, 75% of people (44 of 59) taking BRAFTOVI + MEKTOVI who had never received treatment for metastatic NSCLC saw their tumors shrink or ...

6. 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 ...