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

Trial Summary

What is the purpose of this trial?

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 have advanced non-small cell lung cancer. This study may also see if the combination is safe and may also find the best dose of binimetinib that should be added to pembrolizumab.

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.

What data supports the effectiveness of the drug pembrolizumab for non-small cell lung cancer?

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 is approved for use in patients with this type of cancer and has shown promising results in various studies. ^{1 2 3 4 5}

Is the combination of Binimetinib and Pembrolizumab safe for humans?

Pembrolizumab, also known as KEYTRUDA, has been shown to be generally safe in humans for various conditions, including non-small cell lung cancer and melanoma. Common side effects include issues with the thyroid and lungs, such as hypothyroidism (low thyroid hormone levels) and pneumonitis (lung inflammation). ^{1 2 4 6 7}

What makes the drug combination of Binimetinib and Pembrolizumab unique for treating non-small cell lung cancer?

This treatment combines Binimetinib, which targets specific cancer cell growth pathways, with Pembrolizumab, an immune checkpoint inhibitor that helps the immune system attack cancer cells. This combination is unique because it targets both the cancer cells directly and enhances the body's immune response against them, offering a potentially more effective approach than using either drug alone. ^{1 2 3 5 8}

Research Team

Natasha Leighl, M.D.

Principal Investigator

Princess Margaret Cancer Centre

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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]

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 (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]

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]

References

1. Ireland pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. [2022]

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

Pembrolizumab for the treatment of PD-L1 positive advanced or metastatic non-small cell lung cancer. [2020]

3. France pubmed.ncbi.nlm.nih.gov

[Prolonged response with paclitaxel after immunotherapy by pembrolizumab in lung cancer]. [2017]

4. China 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. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. [2017]

6. New Zealand 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. [2020]

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

FDA Approval Summary: Pembrolizumab for the Treatment of Patients with Unresectable or Metastatic Melanoma. [2022]

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

Perioperative outcomes of pulmonary resection after neoadjuvant pembrolizumab in patients with non-small cell lung cancer. [2022]