Binimetinib + Pembrolizumab for Non-Small Cell Lung Cancer

Recruiting at 1 trial location

Overseen By Natasha Leighl, M.D.

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: University Health Network, Toronto

Must not be taking: Anti-PD-1, MEK inhibitors

Disqualifiers: Pregnancy, Immunodeficiency, Active infection, others

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

Compensation: Varies

Number of Visits: 2

40 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether combining an experimental drug, binimetinib (Mektovi), with pembrolizumab (KEYTRUDA) can benefit individuals with advanced non-small cell lung cancer. The study aims to determine the optimal dose of binimetinib to use with pembrolizumab and assesses the combination's safety. Individuals diagnosed with non-small cell lung cancer who lack certain mutations may be suitable candidates for this trial. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new combination therapy.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot have had certain cancer treatments or investigational drugs recently, and you should not be on chronic steroid therapy or immunosuppressive therapy before starting the trial.

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

Research has shown that pembrolizumab, also known as KEYTRUDA, is generally safe for people. It has been used to treat conditions like non-small cell lung cancer and melanoma, and most people tolerate it well. While side effects can occur, they are often manageable.

For binimetinib, the information is less clear. Some studies suggest it might help with lung cancer, but many indicate it doesn't have a significant impact. Consequently, there is less information about its safety. This study is in an early phase, focusing primarily on assessing the safety of combining these drugs. Early-phase studies typically involve close monitoring to ensure participant safety.

In summary, pembrolizumab is known to be safe for many people, while the safety of binimetinib remains under investigation. Participants in this trial will assist researchers in understanding the safety of these two drugs when used together. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Binimetinib and Pembrolizumab for treating non-small cell lung cancer because it offers a novel approach compared to standard therapies like chemotherapy or targeted drugs. Binimetinib works by targeting the MEK pathway, which is often overactive in cancer cells, while Pembrolizumab is an immunotherapy that helps the immune system recognize and attack cancer cells. This dual action—blocking cancer cell growth while boosting immune response—could potentially be more effective than existing treatments. Additionally, Pembrolizumab's success in other cancers makes researchers hopeful about its potential in this combination.

What evidence suggests that the combination of binimetinib and pembrolizumab could be effective for non-small cell lung cancer?

Studies have shown that pembrolizumab, a drug that helps the immune system fight cancer, works well for advanced non-small cell lung cancer. In this trial, participants will receive a combination of pembrolizumab and binimetinib, an experimental drug. Research suggests that this combination may be promising for treating other cancers, such as metastatic triple-negative breast cancer. Although it remains unconfirmed whether this combination works for non-small cell lung cancer, pembrolizumab's ability to boost the immune response offers hope. Early findings suggest this combination might provide new benefits for patients with advanced lung cancer. ^{2 4 6 7 8}

Who Is on the Research Team?

Natasha Leighl, M.D.

Principal Investigator

Princess Margaret Cancer Centre

Are You a Good Fit for This Trial?

This trial is for adults with advanced non-small cell lung cancer that hasn't spread to the brain, who haven't had recent heart issues or other cancers, and don't have immune system problems. They must not be on certain medications, have a life expectancy over 3 months, can take pills normally, and their organs must work well.

Inclusion Criteria

I can take pills and don't have major stomach or bowel issues affecting drug absorption.

Must agree to use methods to prevent pregnancy as agreed upon between the investigator and the participant for at least 120 days after the last dose of study treatment.

Have a life expectancy of greater than 3 months.

Exclusion Criteria

I have an immune system disorder or have been on high-dose steroids or other immune-weakening medicines recently.

I haven't had cancer treatment or experimental drugs in the last 4 weeks.

I have another cancer that is getting worse or was treated in the last year.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase I Treatment

Participants receive binimetinib and pembrolizumab to determine the safe dose level

28 days

1 visit (in-person) for pembrolizumab administration on Day 8

Phase Ib Treatment

Participants receive the confirmed dose of binimetinib and pembrolizumab to evaluate safety, tolerability, and effectiveness

21 days per cycle

1 visit (in-person) for pembrolizumab administration on Day 1 of each cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

What Are the Treatments Tested in This Trial?

Interventions

• Binimetinib
• Pembrolizumab

Trial Overview Researchers are testing if combining binimetinib (an experimental drug) with pembrolizumab is effective in treating advanced non-small cell lung cancer. The study will also determine the safest dose of binimetinib when used with pembrolizumab.

How Is the Trial Designed?

Group I: Phase 1b Experimental Treatment 2 Interventions

All Cycles = 21 days Binimetinib, by mouth (orally), at the best dose found in Phase 1 of the study, twice a day, continuously. Pembrolizumab, by vein (intravenously), at a dose of 200 mg on Day 1 of every cycle.

Group II: Phase 1 Experimental Treatment 2 Interventions

Cycle 1 = 28 days and Cycle 2 and Future Cycles = 21 days Binimetinib, by mouth (orally): Level 1: 45 mg, twice a day, continuously; Level -1: 30 mg, twice a day, continuously; Level -2: 30 mg, twice a day, for Days 1-14 of each cycle only Pembrolizumab, by vein (intravenously), at a dose of 200 mg on Day 8 of Cycle 1, then Day 1 of Cycle 2 and future cycles.

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 Health Network, Toronto

Lead Sponsor

Trials

1,555

Recruited

526,000+

Published Research Related to This Trial

In a Phase 2 study involving 35 patients with non-small cell lung cancer, neoadjuvant pembrolizumab was found to be safe and well tolerated, with only one surgery delay due to thyroiditis and no mortality within 90 days post-surgery.

The study showed a high rate of R0 resection (88%) and a major pathologic response in 28% of patients, indicating that pembrolizumab may be more effective than standard neoadjuvant chemotherapy in this setting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Perioperative outcomes of pulmonary resection after neoadjuvant pembrolizumab in patients with non-small cell lung cancer. Tong, BC., Gu, L., Wang, X., et al.[2022]

In a phase II trial involving 15 patients with resectable non-small cell lung cancer (NSCLC), neoadjuvant treatment with pembrolizumab showed a major pathologic response in 27% of patients, indicating promising antitumor activity before surgery.

The treatment was found to be feasible and safe, with only 33% of patients experiencing moderate adverse events, and no postoperative mortality, suggesting that pembrolizumab does not compromise surgical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. Eichhorn, F., Klotz, LV., Kriegsmann, M., et al.[2022]

Pembrolizumab (KEYTRUDA) was approved by the FDA for treating unresectable or metastatic melanoma based on two clinical trials involving 1,374 patients, showing significant improvements in overall survival compared to ipilimumab, with hazard ratios indicating a reduced risk of death.

Patients receiving pembrolizumab also experienced significant improvements in progression-free survival, although some immune-mediated adverse reactions like hypothyroidism and pneumonitis were noted, highlighting the importance of monitoring for side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Pembrolizumab for the Treatment of Patients with Unresectable or Metastatic Melanoma. Barone, A., Hazarika, M., Theoret, MR., et al.[2022]

Pembrolizumab, a PD-1 inhibitor, has demonstrated clinical effectiveness in treating various solid tumors, particularly in patients with PD-L1-positive non-small-cell lung cancer and unresectable/metastatic melanoma.

Early-phase trials and ongoing studies are focused on further confirming the clinical benefits of pembrolizumab in thoracic malignancies, highlighting its potential as a significant treatment option in cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. Karim, S., Leighl, N.[2017]

Pembrolizumab monotherapy significantly improved quality-adjusted survival (Q-TWiST) by 2.49 months compared to platinum-based chemotherapy and by 2.29 months compared to docetaxel in patients with advanced non-small cell lung cancer, indicating its efficacy in enhancing patient quality of life.

The benefits of pembrolizumab continued to increase over time, suggesting that it not only offers longer overall survival but also fewer treatment-related adverse events compared to traditional chemotherapy options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Q-TWiST Analysis to Assess Benefit-Risk of Pembrolizumab in Patients with PD-L1-Positive Advanced or Metastatic Non-small Cell Lung Cancer. Huang, M., Pietanza, MC., Samkari, A., et al.[2020]

Pembrolizumab is a safe and effective immune checkpoint inhibitor that targets the PD-1 receptor, currently approved for treating advanced melanoma and metastatic non-small cell lung cancer (NSCLC).

Ongoing studies are exploring the potential of pembrolizumab in combination with other treatments for lung cancer and other cancer types, while also investigating biomarkers that may predict patient response to this therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of PD-L1 positive advanced or metastatic non-small cell lung cancer. Dang, TO., Ogunniyi, A., Barbee, MS., et al.[2020]

A 68-year-old patient with stage IV lung adenocarcinoma showed an unexpected positive response to paclitaxel after failing treatment with pembrolizumab, an anti-PD-1 immunotherapy.

The patient experienced a response duration of over fourteen months with paclitaxel, suggesting that combining or sequencing chemotherapy with immunotherapy may enhance treatment effectiveness in certain cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Prolonged response with paclitaxel after immunotherapy by pembrolizumab in lung cancer]. Zapata, E., Mennecier, B., Leduc, C., et al.[2017]

In a study of 24 patients with advanced non-small cell lung cancer (NSCLC) treated with pembrolizumab, the objective response rate was 45.8%, indicating that nearly half of the patients experienced a reduction in tumor size after treatment.

Pembrolizumab showed promising results even in PD-L1-negative patients, with a major pathological response of 75% and a pathological complete response of 50% in those who underwent surgery, suggesting its potential effectiveness across different patient profiles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of pembrolizumab for the treatment of advanced non-small cell lung cancer: a retrospective, single-centre, single-arm study. Guo, T., Ding, Y., Chen, L., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT03991819

NCT03991819 | Study of Binimetinib in Combination With ... This is a Phase I/Ib study whose purpose is to find out if combining an experimental drug called binimetinib with pembrolizumab is beneficial in people who ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12079099/

Pembrolizumab in Combination with Binimetinib in Patients ... Pembrolizumab, in combination with a MEK inhibitor, binimetinib, has promising activity in metastatic triple-negative breast cancer, particularly in patients ...

3. withpower.com withpower.com/trial/phase-1-carcinoma-non-small-cell-lung-8-2019-6d498

Binimetinib + Pembrolizumab for Non-Small Cell Lung ... Research shows that pembrolizumab, a drug that helps the immune system fight cancer, is effective and safe for treating advanced non-small cell lung cancer. It ...

4. mycancergenome.org mycancergenome.org/content/clinical_trials/NCT03991819/

Clinical Trial: NCT03991819 This is a Phase I/Ib study whose purpose is to find out if combining an experimental drug called binimetinib with pembrolizumab is beneficial in people who ...

5. aacrjournals.org aacrjournals.org/clincancerres/article/30/17/3768/747261/A-Phase-II-Study-of-Potentiation-of-Pembrolizumab

A Phase II Study of Potentiation of Pembrolizumab with ... The combination of pembrolizumab, binimetinib, and bevacizumab failed to meet its primary endpoint of higher objective response rate compared with historical ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11295668/

The safety and efficacy of binimetinib for lung cancer Only a few studies have shown binimetinib to be effective, in terms of improving OS, PFS, and ORR, while most of the studies found nonsignificant efficacy with ...

7. esmoopen.com esmoopen.com/article/S2059-7029(24)00418-6/fulltext

71P A phase I study of binimetinib, a MEK inhibitor, in ... We combined binimetinib with pembrolizumab in patients with stage IV advanced non-small cell lung cancer (NSCLC) and PD-L1 tumor proportion score>=50%. Methods.

8. aacrjournals.org aacrjournals.org/cancerres/article/83/8_Supplement/CT206/725348/Abstract-CT206-A-phase-I-study-of-binimetinib-a

Abstract CT206: A phase I study of binimetinib, a MEK inhibitor ... We combined binimetinib with pembrolizumab in patients with stage IV advanced non-small cell lung cancer (NSCLC) and PD-L1 tumor proportion score>=50%.