Lung CancerPhase 1NCT03170206
Study of Palbociclib in Combination With Binimetinib for Patients With Advanced KRAS Mutant Non-Small Cell Lung Cancer
A Phase 1 study testing Binimetinib and Palbociclib in people with Lung Cancer, run by Dana-Farber Cancer Institute at 1 site in United States.
Trial summary
This trial is being conducted as a possible treatment for lung cancer with a specific change in the KRAS gene. The drugs involved in this study are: Palbociclib Binimetinib Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Lung Cancer
- What is being tested?
- Binimetinib and Palbociclib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 34 participants
- Where
- 1 siteUnited States
- Study dates
- 31 May 2017to 31 Dec 2025
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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
- Participants must have histologically confirmed advanced NSCLC (with a confirmed KRAS mutation via any CLIA-certified method) for which curable treatment modalities are not an option
- Part I Dose Escalation: Participants are required to have measurable disease per RECIST 1.1 within 4 weeks of study entry
- MTD Expansion and Part II: Participants must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as > 20 mm with conventional techniques or as > 10 mm with spiral CT scan. See section 10 for the evaluation of measureable disease.
- Age ≥ 18 years. Because no dosing or adverse event data are currently available in participants < 18 years of age, children are excluded from this study
- Participants are permitted to have any number of prior therapies prior to enrollment
- ECOG performance status < 2 (see Appendix A).
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- Participants must have normal organ and marrow function as defined below:
- Absolute neutrophil count > 1,500mm3
- Hemoglobin > 9 g/dL
- Platelets > 100,000/mcL
- Total bilirubin < 2 X institutional upper limit of normal (ULN)
- AST (SGOT)/ALT (SGPT) < 2.5 X ULN -OR-
- AST (SGOT)/ALT (SGPT) < 5.0 X ULN if hepatic metastases are present
- Creatinine < 1.5 X the institutional ULN -OR-
- Calculated creatinine clearance (determined as per Cockcroft-Gault) > 50 mL/min
- The effects of palbociclib and binimetinib on the developing human fetus are not fully known. For this reason, women of child-bearing potential and men must agree to use adequate contraception (combination hormonal and barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 90 days after discontinuation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
- Ability to understand and the willingness to sign a written informed consent document.
- The availability of archival tissue to evaluate retrospectively the participant's Rb status. The requirement is a minimum of 5 unstained slides with each tissue cut measuring 4 microns in width. Ideally 15 slides will be requested. Patients without available archival tissue may be enrolled at the discretion of the principal investigator.
- Patients must have recovered to ≤ Grade 1 in terms of toxicity from prior treatments (excluding neuropathy which can be ≤ Grade 2, and alopecia).
- MTD Expansion: Patients must be willing to undergo pre- and on-treatment tumor biopsies. Patients are exempt from this requirement if, in the opinion of the investigator, the biopsy procedure would pose a significant risk or if they have only pulmonary metastatic disease.
- Patients must be able to take oral medications.
- Patients must have adequate cardiac function, defined as:
- Left ventricular ejection fraction (LVEF) > 50% as determined by echocardiogram or multigated acquisition scan (MUGA).
- QTc < 480 msec.
Who cannot join
- Participants who have had chemotherapy, radiotherapy, or major surgery within 2 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study.
- Participants receiving any other study agents concurrently with the study drugs.
- Participants with symptomatic brain metastases that require chronic steroids. Patients with a history of brain metastases are permitted to enroll as long as they have been treated, are off of steroids, and have been stable for a minimum of one month on imaging.
- MTD Expansion: Patients currently taking anticoagulants and who cannot safely hold the medication to facilitate pre and on-treatment tumor biopsies are excluded from participation.
- Concurrent use of strong CYP3A4 inhibitors/inducers is prohibited due to drug-drug interactions with palbociclib. Moderate CYP3A4 inhibitors/inducers should be used with caution (see Appendix C).
- Part I Dose Escalation: Concurrent use of proton-pump inhibitors (PPIs) is prohibited.
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- Uncontrolled intercurrent illness including, but not limited to:
- ongoing or active infection requiring systemic treatment
- symptomatic congestive heart failure
- cardiac arrhythmia
- psychiatric illness/social situations that would limit compliance with study requirements
- hypertension, defined as systolic blood pressure > 160 mmHg despite medical management
- myocardial infarction, unstable angina, coronary artery bypass grafting, coronary angioplasty, or stenting < 6 months prior to screening
- History of QT syndrome, Brugada syndrome, known history of QTc prolongation, or Torsades de Pointes.
- History of Gilbert's syndrome.
- History of neuromuscular disorders that are associated with elevated CK (e.g. inflammatory myopathies, muscular dystrophy, amyotrophic lateral sclerosis, spinal muscular atrophy).
- History of other malignancy which could affect compliance with the protocol or interpretation of results. History of curatively treated basal or squamous cell carcinoma of the skin or in situ carcinoma of the cervix are allowed. Subjects with a malignancy that has been treated with curative intent will also be allowed if the malignancy has been in remission without treatment for ≥ 2 years prior to Cycle 1, Day 1. Subjects with localized prostate cancer that has been treated with curative intent will be allowed
- Patients planning to embark on a new strenuous exercise regimen after the first dose of study treatment.
- History of a malabsorption syndrome or uncontrolled nausea, vomiting, or diarrhea that may interfere with the absorption of oral study medication in the opinion of the investigator.
- Pregnant women are excluded from this study because the study agents have the potential for teratogenic or abortifacient effects. As there is an unknown but potential risk of adverse events in nursing infants secondary to treatment of the mother with the study agents, breastfeeding must be discontinued if the mother is treated.
- Part II: Individuals with a history of a different malignancy are ineligible except for the following circumstances:
- They have been disease-free for at least 3 years and are deemed by the investigator to be at low risk for recurrence of that malignancy.
- Individuals with the following cancers are eligible if diagnosed and curatively treated within the past 5 years: cervical cancer in situ, and basal or squamous cell carcinoma of the skin.
- Known HIV-positive individuals on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions. Appropriate studies will be undertaken in participants receiving combination antiretroviral therapy when indicated.
- Patients with known active hepatitis B and/or active hepatitis C infection.
- Evidence of visible retinal pathology on screening ophthalmologic examination that places the participant at an unacceptable risk for retinal vein occlusion (e.g. uncontrolled glaucoma or ocular hypertension, history of hyperviscosity, etc.).
- History of retinal degenerative disease.
- Presence of neurosensory retinal detachment, retinal vein occlusion (RVO), or neovascular macular degeneration on screening ophthalmologic exam.
Trial locations and contacts
1 site in 1 country.
United States1 site
Dana Farber Cancer Institute
Boston, Massachusetts, 02215
About this study
Official title: Phase I Study of the CDK4/6 Inhibitor Palbociclib (PD-0332991) in Combination With the MEK Inhibitor Binimetinib (MEK162) for Patients With Advanced KRAS Mutant Non-Small Cell Lung Cancer
This trial is being conducted as a possible treatment for lung cancer with a specific change in the KRAS gene.
The drugs involved in this study are:
- Palbociclib
- Binimetinib
Read the detailed description
This research study is a Phase I clinical trial. Participants are being asked to participate in the Phase I portion of the study. A Phase I clinical trial tests the safety of an investigational intervention and also tries to define the appropriate dose of the investigational intervention to use for further studies. "Investigational" means that the intervention is being studied.
Palbociclib is an oral drug which has been shown to stop the cell cycle, which is the way a cell initiates growth. Binimetinib is also an oral drug which stops a signal that a cell receives, instructing it to grow. By putting these two drugs together the investigators hope that it will have a greater affect on cancer growth than either drug alone. The FDA (the U.S. Food and Drug Administration) has not approved binimetinib as a treatment for any disease. The FDA has not approved palbociclib for use in lung cancer but it has been approved for other cancer types.
The purpose of this study is to:
- Test the combination of these two drugs, Palbociclib and Binimetinib, in order to determine a safe and tolerable dose of the combination
- Determine the response rate of the combination
- Further evaluate the safety and side effect profile for the combination of palbociclib and binimetinib.
- Conditions
- Lung Cancer
- Being tested
- Binimetinib, Palbociclib
- Keywords
- Lung Cancer
- Medical subject headings
- Lung Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BinimetinibDrug
Also called MEK162
Binimetinib is also an oral drug which stops a signal that a cell receives, instructing it to grow.
PalbociclibDrug
Also called IBRANCE
It is a selective inhibitor of the cyclin-dependent kinases CDK4 and CDK6
| Study group | Role | What they receive |
|---|---|---|
| Binimetinib Combine with Palbociclib Phase 1 | Experimental | * Palbociclib will be administered orally once daily
* Patients will be dosed with palbociclib for three weeks out of every four weeks per cycle
* Binimetinib will be administered orally twice daily
* Patients will be dosed with Binimetinib continuously through the four weeks per cycle Receives: Drug: Binimetinib; Drug: Palbociclib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum Tolerated Dose
A standard 3+3 design will be implemented to discover the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of the combination of study drugs. A dose will be declared the MTD if zero or 1 patient out of 6 experience a dose limiting toxicity (DLT) at the highest dose level below the maximally administered dose. This is generally the Recommended Phase 2 dose- RP2D
Measured: 2 years
Safety and tolerability of Palbocilib and Binimetinib
Toxicities will be graded using version 4.0 of the NCI Common Terminology Criteria for Adverse Events (CTCAE).
Measured: 2 Years
progression free survival
Determine the proportion of patients who are alive and progression-free at 4 months in the binimetinib, palbociclib and combination arms.
Measured: 4 months
Secondary outcomes (3)
Pharmacokinetic parameters of palbociclib and binimetinib
The pharmacokinetic properties-Cmax maximum plasma concentration for the combination of palbociclib and binimetinib will be evaluated utilizing serial blood draws on cycle 1 day 1 and a steady state trough level drawn on cycle 1 day 15.
Measured: 15 days
Target engagement of palbociclib and binimetinib
Confirm target engagement of palbociclib and binimetinib in pre- and on-treatment tumor biopsies from patients enrolled to an MTD expansion cohort.
Measured: 2 years
Objective Response
Determine the best objective response rate, as determined by RECIST 1.1, of the combination of palbociclib and binimetinib, palbociclib alone and binimetinib alone in patients with advanced KRAS mutant NSCLC.
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 posted30 May 2017
- Study start31 May 2017
- Primary completion28 Feb 2023
- Study completion31 Dec 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Lung CancerStudies of the same condition, open and under way.
- More trials run by Dana-Farber Cancer InstituteThe 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
- Not applicable
- Intervention model
- Single group
- Model description
- Phase 1 is a single group standard 3+3 dose escalation
- Masking
- None (open label)
- Enrolment
- 34 participants (actual)
Sponsor and investigators
- Lead sponsor
- Dana-Farber Cancer Institute
- Sponsor type
- University, hospital or other
- Collaborators
- Pfizer, Array BioPharma
- Responsible party
- Principal investigator, Geoffrey Shapiro, MD, PhD, Dana-Farber Cancer Institute
- Investigators
- Geoffrey Shapiro, MD, PhD, Principal investigator, Dana-Farber Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03170206
- Sponsor's protocol ID
- 16-531
- Status last verified
- Feb 2026
- First submitted
- 19 May 2017
- Last updated
- 12 Feb 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 12 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Study of the CDK4/6 Inhibitor Palbociclib (PD-0332991) in Combination With the MEK Inhibitor Binimetinib (MEK162) for Patients With Advanced KRAS Mutant Non-Small Cell Lung Cancer
- ClinicalTrials.gov ID
- NCT03170206
- Acronym / sponsor ID
- 16-531
- Conditions
- Lung Cancer
- Keywords
- Lung Cancer
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 34 participants (actual)
- Lead sponsor
- Dana-Farber Cancer InstituteUniversity, hospital or other
- Collaborators
- Pfizer, Array BioPharma
- Study start
- 31 May 2017 (actual)
- Primary completion
- 28 Feb 2023 (actual)
- Study completion
- 31 Dec 2025 (actual)
- First posted
- 30 May 2017 (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 trial is being conducted as a possible treatment for lung cancer with a specific change in the KRAS gene.
The drugs involved in this study are:
- Palbociclib
- Binimetinib
Detailed description
This research study is a Phase I clinical trial. Participants are being asked to participate in the Phase I portion of the study. A Phase I clinical trial tests the safety of an investigational intervention and also tries to define the appropriate dose of the investigational intervention to use for further studies. "Investigational" means that the intervention is being studied.
Palbociclib is an oral drug which has been shown to stop the cell cycle, which is the way a cell initiates growth. Binimetinib is also an oral drug which stops a signal that a cell receives, instructing it to grow. By putting these two drugs together the investigators hope that it will have a greater affect on cancer growth than either drug alone. The FDA (the U.S. Food and Drug Administration) has not approved binimetinib as a treatment for any disease. The FDA has not approved palbociclib for use in lung cancer but it has been approved for other cancer types.
The purpose of this study is to:
- Test the combination of these two drugs, Palbociclib and Binimetinib, in order to determine a safe and tolerable dose of the combination
- Determine the response rate of the combination
- Further evaluate the safety and side effect profile for the combination of palbociclib and binimetinib.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Phase 1 is a single group standard 3+3 dose escalation
| Arm | Type | Receives |
|---|---|---|
| Binimetinib Combine with Palbociclib Phase 1 | Experimental | Drug: Binimetinib, Drug: Palbociclib* Palbociclib will be administered orally once daily * Patients will be dosed with palbociclib for three weeks out of every four weeks per cycle * Binimetinib will be administered orally twice daily * Patients will be dosed with Binimetinib continuously through the four weeks per cycle |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (24 listed)
- Participants must have histologically confirmed advanced NSCLC (with a confirmed KRAS mutation via any CLIA-certified method) for which curable treatment modalities are not an option
- Part I Dose Escalation: Participants are required to have measurable disease per RECIST 1.1 within 4 weeks of study entry
- MTD Expansion and Part II: Participants must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as > 20 mm with conventional techniques or as > 10 mm with spiral CT scan. See section 10 for the evaluation of measureable disease.
- Age ≥ 18 years. Because no dosing or adverse event data are currently available in participants < 18 years of age, children are excluded from this study
- Participants are permitted to have any number of prior therapies prior to enrollment
Key exclusion criteria (28 listed)
- Participants who have had chemotherapy, radiotherapy, or major surgery within 2 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study.
- Participants receiving any other study agents concurrently with the study drugs.
- Participants with symptomatic brain metastases that require chronic steroids. Patients with a history of brain metastases are permitted to enroll as long as they have been treated, are off of steroids, and have been stable for a minimum of one month on imaging.
- MTD Expansion: Patients currently taking anticoagulants and who cannot safely hold the medication to facilitate pre and on-treatment tumor biopsies are excluded from participation.
- Concurrent use of strong CYP3A4 inhibitors/inducers is prohibited due to drug-drug interactions with palbociclib. Moderate CYP3A4 inhibitors/inducers should be used with caution (see Appendix C).
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 |
|---|---|---|
| BinimetinibAlso: MEK162Binimetinib is also an oral drug which stops a signal that a cell receives, instructing it to grow. | Drug | Binimetinib Combine with Palbociclib Phase 1 |
| PalbociclibAlso: IBRANCEIt is a selective inhibitor of the cyclin-dependent kinases CDK4 and CDK6 | Drug | Binimetinib Combine with Palbociclib Phase 1 |
Primary outcome
Maximum Tolerated Dose
Time frame: 2 years
A standard 3+3 design will be implemented to discover the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of the combination of study drugs. A dose will be declared the MTD if zero or 1 patient out of 6 experience a dose limiting toxicity (DLT) at the highest dose level below the maximally administered dose. This is generally the Recommended Phase 2 dose- RP2D
Safety and tolerability of Palbocilib and Binimetinib
Time frame: 2 Years
Toxicities will be graded using version 4.0 of the NCI Common Terminology Criteria for Adverse Events (CTCAE).
progression free survival
Time frame: 4 months
Determine the proportion of patients who are alive and progression-free at 4 months in the binimetinib, palbociclib and combination arms.
3 secondary outcomes
Pharmacokinetic parameters of palbociclib and binimetinib
Time frame: 15 days
Target engagement of palbociclib and binimetinib
Time frame: 2 years
Objective Response
Time frame: 2 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Feb 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.
Geoffrey Shapiro, MD, PhD principal investigator
Dana-Farber Cancer Institute
1 site 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 Palbociclib in people with Lung Cancer, run by Dana-Farber Cancer Institute at 1 site in United States.
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 24 inclusion and 28 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: finished, as of the sponsor's last update on 12 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Maximum Tolerated Dose (time frame: 2 years). The study lists 3 primary outcomes in all. 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 12 Feb 2026.