Non-small Cell CarcinomaPhase 1BiniPembroNCT03991819
Study of Binimetinib in Combination With Pembrolizumab in Advanced Non-Small Cell Lung Cancer
A Phase 1 study testing Binimetinib and Pembrolizumab in people with Non-small Cell Carcinoma, run by University Health Network, Toronto at 4 sites in Canada.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Non-small Cell Carcinoma
- What is being tested?
- Binimetinib and Pembrolizumab
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 4 sitesCanada
- Study dates
- 20 Sep 2019to Dec 2026
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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.
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- 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.
- Has a known history of active (untreated) bacillus tuberculosis (TB).
- Has a history or current evidence/risk of retinal vein occlusion (RVO) or predisposing factors to RVO
- Has a history of retinal degenerative disease.
- Has a history of Gilbert's syndrome
- Has any factors that increase the risk of QTc prolongation or risk of arrhythmic events or baseline QTcB interval >480 msec
- Has a history of acute coronary syndromes, coronary artery bypass grafting, angioplasty, or stenting within the past 6 months prior to screening or cardiac metastases.
- Has history or evidence of current clinically significant uncontrolled arrhythmias.
- Has a history or evidence of current ≥Class II congestive heart failure as defined by New York Heart Association (NYHA).
- Has an intra-cardiac defibrillator or permanent pacemaker.
- Has treatment-refractory hypertension defined as a systolic blood pressure >140 mmHg and/or diastolic >90 mmHg which cannot be controlled by anti-hypertensive therapy.
- Has a history of neuromuscular disorders associated with elevated creatine phosphokinase (CK).
- Is planning to embark on a new strenuous exercise regimen after the first dose of study treatment.
- Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the subject's participation for the full duration of the study, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
- Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
- Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of trial treatment.
Trial locations and contacts
4 sites in 1 country.
Canada4 sites
Arthur J.E. Child Comprehensive Cancer Centre
Calgary, Alberta, T2N 4N2
Allan Blair Cancer Centre
Regina, Saskatchewan, S4T 7T1
Saskatoon Cancer Centre
Saskatoon, Saskatchewan, S7N 4H4
Princess Margaret Cancer Centre
Toronto, Ontario, M5G 1Z5
About this study
Official title: Phase I/Ib Study of Binimetinib, a MEK Inhibitor, in Combination With Pembrolizumab in Patients With Advanced Non-Small Cell Lung Cancer (NSCLC)
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.
Read the detailed description
This study will have two parts:
Phase I - During this part, also called the dose de-escalation part, an initial group of 6 participants will receive a certain planned dose of binimetinib in addition to a standard dose of pembrolizumab. If this combination is found to be safe during the first 28 days of receiving the study drugs, this will be considered the most appropriate dose of the study drug combination (the highest dose of binimetinib that can be given with pembrolizumab without causing serious side effects).
Phase Ib - Once the appropriate dose of binimetinib is confirmed in Phase I (as described above), additional participants will be enrolled in the Phase Ib to further test how safe, tolerable, and effective the study drugs at that dose level. Phase Ib will also evaluate the anti-tumour activity of binimetinib and pembrolizumab in participants with advanced non-small cell lung cancer.
- Conditions
- Non-small Cell Carcinoma
- Being tested
- Binimetinib, Pembrolizumab
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BinimetinibDrug
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.
PembrolizumabDrug
Also called Keytruda
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: Binimetinib; Drug: Pembrolizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Objective response rate (ORR)
Per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
Measured: 2 years
Secondary outcomes (2)
Recommended phase 2 dose
Dose level 1, -1, or -2, per dose-limiting toxicities
Measured: 28 days
Incidence of adverse events
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Jun 2019
- Study start20 Sep 2019
- Primary completionAug 2026 (estimated)
- Study completionDec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Non-small Cell CarcinomaStudies of the same condition, open and under way.
- More trials run by University Health Network, TorontoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Health Network, Toronto
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Natasha Leighl, M.D., Principal investigator, Princess Margaret Cancer Centre
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03991819
- Sponsor's protocol ID
- BiniPembro
- Other IDs
- CAPCR 18-5856
- Acronym
- BiniPembro
- Status last verified
- Jun 2026
- First submitted
- 18 Jun 2019
- Last updated
- 23 Jun 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 23 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I/Ib Study of Binimetinib, a MEK Inhibitor, in Combination With Pembrolizumab in Patients With Advanced Non-Small Cell Lung Cancer (NSCLC)
- ClinicalTrials.gov ID
- NCT03991819
- Acronym / sponsor ID
- BiniPembro / BiniPembro
- Conditions
- Non-small Cell Carcinoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- University Health Network, TorontoUniversity, hospital or other
- Study start
- 20 Sep 2019 (actual)
- Primary completion
- Aug 2026 (estimated)
- Study completion
- Dec 2026 (estimated)
- First posted
- 19 Jun 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
This study will have two parts:
Phase I - During this part, also called the dose de-escalation part, an initial group of 6 participants will receive a certain planned dose of binimetinib in addition to a standard dose of pembrolizumab. If this combination is found to be safe during the first 28 days of receiving the study drugs, this will be considered the most appropriate dose of the study drug combination (the highest dose of binimetinib that can be given with pembrolizumab without causing serious side effects).
Phase Ib - Once the appropriate dose of binimetinib is confirmed in Phase I (as described above), additional participants will be enrolled in the Phase Ib to further test how safe, tolerable, and effective the study drugs at that dose level. Phase Ib will also evaluate the anti-tumour activity of binimetinib and pembrolizumab in participants with advanced non-small cell lung cancer.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Phase 1 | Experimental | Drug: Binimetinib, Drug: PembrolizumabCycle 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. |
| Phase 1b | Experimental | Drug: Binimetinib, Drug: PembrolizumabAll 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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.
Key exclusion criteria (30 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BinimetinibBinimetinib 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. | Drug | Phase 1, Phase 1b |
| PembrolizumabAlso: KeytrudaPembrolizumab 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. | Drug | Phase 1, Phase 1b |
Primary outcome
Objective response rate (ORR)
Time frame: 2 years
Per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
2 secondary outcomes
Recommended phase 2 dose
Time frame: 28 days
Incidence of adverse events
Time frame: 2 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Jun 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Natasha Leighl, M.D. principal investigator
Princess Margaret Cancer Centre
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Binimetinib and Pembrolizumab in people with Non-small Cell Carcinoma, run by University Health Network, Toronto at 4 sites in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 30 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 23 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Objective response rate (ORR) (time frame: 2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Jun 2026.