Study of Palbociclib in Combination With Binimetinib for Patients With Advanced KRAS Mutant Non-Small Cell Lung Cancer

NCT03170206 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: 16-531
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 1

Brief 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

Conditions

Lung Cancer

Keywords

Lung Cancer

Outcome Measures

Primary Outcomes (3)

• 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

  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).

  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.

  4 months

Secondary Outcomes (3)

• Pharmacokinetic parameters of palbociclib and binimetinib

  15 days

• Target engagement of palbociclib and binimetinib

  2 years

• Objective Response

  2 years

Study Arms (1)

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

Drug: Binimetinib; Drug: Palbociclib

Interventions

Binimetinib DRUG

Binimetinib is also an oral drug which stops a signal that a cell receives, instructing it to grow.

Also known as: MEK162

Binimetinib Combine with Palbociclib Phase 1

Palbociclib DRUG

It is a selective inhibitor of the cyclin-dependent kinases CDK4 and CDK6

Also known as: IBRANCE

Binimetinib Combine with Palbociclib Phase 1

Eligibility Criteria

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

You may qualify if:

• 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).
• 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

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Dana-Farber Cancer Institute: lead
• Pfizer: collaborator
• Array BioPharma: collaborator

Study Sites (1)

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

MeSH Terms

Conditions

Lung Neoplasms

Interventions

binimetinib; palbociclib

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Geoffrey Shapiro, MD, PhD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, PhD

Model Details: Phase 1 is a single group standard 3+3 dose escalation

Study Record Dates

• First Submitted: May 19, 2017
• First Posted: May 30, 2017
• Study Start: May 31, 2017
• Primary Completion: February 28, 2023
• Study Completion: December 31, 2025
• Last Updated: February 12, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)