Study of Binimetinib in Combination With Pembrolizumab in Advanced Non-Small Cell Lung Cancer

NCT03991819 | Recruiting Phase 1 DMC

• 2 other identifiers: BiniPembroCAPCR 18-5856
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 4

Brief Summary

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.

Conditions

Non-small Cell Carcinoma

Outcome Measures

Primary Outcomes (1)

• Objective response rate (ORR)

  Per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1

  2 years

Secondary Outcomes (2)

• Recommended phase 2 dose

  28 days

• Incidence of adverse events

  2 years

Study Arms (2)

Phase 1

EXPERIMENTAL

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.

Drug: Binimetinib; Drug: Pembrolizumab

Phase 1b

EXPERIMENTAL

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.

Drug: Binimetinib; Drug: Pembrolizumab

Interventions

Binimetinib DRUG

Binimetinib is a drug that, inside the cell, blocks an important series of chemical reactions called a molecular pathway. Binimetinib blocks the MEK1/2 pathway from working. In some types of cancers, this pathway becomes too active, which can cause tumor cell growth. Blocking the MEK1/2 pathway from working is thought to slow or stop tumor cell growth.

Phase 1; Phase 1b

Pembrolizumab DRUG

Pembrolizumab is an immunotherapy drug that is approved by Health Canada for the treatment of patients with PD-L1 positive non-small cell lung cancer as a first treatment. PD-1 is a type of protein that binds to another type of protein known as PD-L1. When these proteins bind together, it helps prevent cells from killing each other, including cancer cells. Some drugs, like pembrolizumab, are used to block PD-1 from binding to PD-L1. When the protein is blocked, the body's immune system can kill more cells.

Also known as: Keytruda

Phase 1; Phase 1b

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed diagnosis of non-small cell lung carcinoma with tumour PDL-1 TPS≥50% by 22C3 pharmDx immunohistochemistry. Patients must have EGFR wild-type, ALK-rearrangement negative metastatic or advanced NSCLC (stage IV or incurable stage III). Patients with neuroendocrine (carcinoid) carcinoma, small cell or mixed small cell and non-small cell carcinoma are not eligible.
• 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.
• The participant provides written informed consent for the trial.
• Have measurable disease.
• Provide archival tumor tissue sample for KRAS/BRAF/STK11 mutation analysis or newly obtained core or excisional biopsy of a tumor lesion not previously irradiated.
• Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
• Have a life expectancy of greater than 3 months.
• Be able to swallow and retain oral medication and not have any clinically significant gastrointestinal abnormalities that may alter absorption such as malabsorption syndrome or major resection of the stomach or bowels.
• Have adequate organ function.

You may not qualify if:

• Female with positive urine pregnancy test.
• Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor, or a prior MEK inhibitor.
• Has received prior systemic anti-cancer therapy including investigational agents within 4 weeks prior to registration, excluding supportive medications such as bisphosphonates.
• Has received prior radiotherapy within 2 weeks of start of study treatment. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-central nervous system disease.
• Has received a live vaccine within 30 days prior to the first dose of study drug.
• Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study treatment.
• Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug.
• Has a known additional malignancy that is progressing or has required active treatment within the past year.
• Has known active central nervous system metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable, clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study treatment.
• Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients, or history of allergic reactions attributed to compounds of similar composition to binimetinib.
• Has active autoimmune disease that has required systemic treatment in the past 2 years.
• Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
• Has an active infection requiring systemic therapy.
• Has a known history of Human Immunodeficiency Virus.
• Has a known history of Hepatitis B or known active Hepatitis C virus infection.

Sponsors & Collaborators

• University Health Network, Toronto: lead

Study Sites (4)

Arthur J.E. Child Comprehensive Cancer Centre

Calgary, Alberta, T2N 4N2, Canada

RECRUITING

Princess Margaret Cancer Centre

Toronto, Ontario, M5G 1Z5, Canada

RECRUITING

Allan Blair Cancer Centre

Regina, Saskatchewan, S4T 7T1, Canada

RECRUITING

Saskatoon Cancer Centre

Saskatoon, Saskatchewan, S7N 4H4, Canada

RECRUITING

MeSH Terms

Interventions

binimetinib; pembrolizumab

Study Officials

• Natasha Leighl, M.D.

  Princess Margaret Cancer Centre

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Natasha Leighl, M.D.

CONTACT

416-946-4645; natasha.leighl@uhn.ca

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 18, 2019
• First Posted: June 19, 2019
• Study Start: September 20, 2019
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: December 5, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

CA (4)