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


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Primary Outcome Measures:

  • 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.

Secondary Outcome Measures:

  • Pharmacokinetics [ Time Frame: 15 days ]

    The pharmacokinetic properties-Cmax maximum plasma concentration for the combination of palbociclib and PD-0325901 will be evaluated utilizing serial blood draws on cycle 1 day 1 and a steady state trough level drawn on cycle 1 day 15.

  • Target engagement of palbociclib and binimetinib [ Time Frame: 2 years ]

    Confirm target engagement of palbociclib and binimetinib in pre- and on-treatment tumor biopsies from patients enrolled to an MTD expansion cohort.

  • Objective Response [ Time Frame: 2 years ]

    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.

This research study is a Phase I/II 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.